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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

FORM 10-K

ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 20212023
OR
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from    to
Commission file number 001-04321001-39990
ANGION BIOMEDICA CORPElicio Therapeutics, Inc.
(Exact name of registrant as specified in its charter)
Delaware11-3430072
(State or other jurisdiction of
incorporation or organization)
(I.R.S. Employer Identification No.)
51 Charles Lindbergh Boulevard, Uniondale, New York451 D Street, 5th Floor, Boston, Massachusetts1155302210
(Address of Principal Executive Offices)(Zip Code)
(415) 655-4899(857) 209-0050
Registrant's telephone number, including area code

Securities registered pursuant to Section 12(b) of the Act:
Title of each classTrading Symbol(s)Name of each exchange on which registered
Common Stock, par value $0.01ANGNELTXThe Nasdaq Global Select Market
Securities registered pursuant to section 12(g) of the Act: None.
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes No
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes No
Indicate by check mark whether the registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports); and (2) has been subject to such filing requirements for the past 90 days. Yes No
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-(§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes No
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filerAccelerated filer
Non-accelerated filerSmaller reporting company
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report.
If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the Registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐
Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the Registrant's executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes No
The aggregate market value of the voting stock and non-voting common stock held by non-affiliates of the registrant, based on the closing price of a share of the registrant’s common stock on June 30, 20212023 as reported by the Nasdaq Global Select Market on such date, was approximately $365$47.1 million. Shares of common stock held by each executive officer and director and by each entity affiliated with an executive officer or and director have been excluded from this computation. The determination of affiliate status for this purpose is not necessarily a conclusive determination for other purposes.
The number of shares of the issuer’s common stock outstanding as of March 25, 2022,26, 2024, was 29,958,064.10,235,469.
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the registrant’s definitive proxy statement relating to the 2022be filed for its 2024 Annual Meeting of Stockholders whichare incorporated by reference into Part III hereof. Such proxy statement will be filed with the Securities and Exchange Commission within 120 days afterof the end of the registrant’s fiscal year ended December 31, 2021, are incorporatedcovered by reference into Part III of this Annual Report on Form 10-K.
Auditor Name: Baker Tilly US, LLPAuditor Location: Tewksbury, MassachusettsPCAOB ID: 23
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TABLE OF CONTENTS
PART IPage
PART II
PART III
PART IV









Forward-Looking Statements

This Annual Report on Form 10-K, including the sections titled “Business”, “Risk Factors,” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations”, contains “forward-looking statements”forward-looking statements within the meaning of Section 21E of the Private Securities ExchangeLitigation Reform Act of 1934, as amended, or the Exchange Act.1995. All statements other than statements of historical facts contained in this Annual Report on Form 10-K other than statements of historical fact, including statements concerning our business strategy and plans, future operating results and financial position, as well as our objectives and expectations for our future operations, are statements that could be deemedforward-looking statements.
In some cases, you can identify forward-looking statements reflecting the current beliefs and expectations of management with respect to future events or to our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by these forward-looking statements. These statements are often identified by the use of wordsterminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “due,” “estimate,” “expect,” “goal,” “if,” “intend,” “may,” “objective,” “plan,” “predict,” “potential,” “positioned,” “seek,” “should,” “target,” “will,” “would,” “until” and other similar expressions that are predictions of or variations. Forward-lookingindicate future events and future trends, or the negative of these terms or other comparable terminology. These forward-looking statements contained in this Annual Report on Form 10-K include, but are not limited to, statements about:

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Tableour financial condition, including our ability to obtain the funding necessary to advance the development of Contents
ELI-002 and any other future product candidates, our ability to continue as a going concern and our cash runway;
the potential benefits, activity, effectivenessability of our clinical trials to demonstrate safety and safetyefficacy of our product candidates, and other positive results;
our ability to utilize our platform to develop a pipeline of product candidates to address unmet needs in cancer and infectious disease;
the timing, progress and results of clinical trials for ELI-002, and other product candidates we may develop, including statements regarding the timing of initiation and completion of studies or trials and related preparatory work, the period during which the results of the studies or trials will become available, and research and development programs;
the timing, scope and likelihood of regulatory filings and approvals, including timing of INDs (as defined below) and U.S. Food and Drug Administration (“FDA”) approval of ELI-002 and any future product candidates;
the successtiming, scope or likelihood of foreign regulatory filings and timingapprovals;
our ability to develop and advance current product candidates and programs into, and successfully complete, clinical studies;
our manufacturing, commercialization, and marketing capabilities and strategy;
the need to hire additional personnel and our ability to attract and retain such personnel;
the size of the market opportunity for our product candidates, including estimates of the number of patients who suffer from the diseases we are targeting;
expectations regarding the approval and use of our preclinical studiesproduct candidates in combination with other drugs;
expectations regarding potential for accelerated approval or other expedited regulatory designation;
our competitive position and the success of competing therapies that are or may become available;
our anticipated research and development activities and projected expenditures;
existing regulations and regulatory developments in the United States, Europe and other jurisdictions;
the extent to which global economic and political developments, including the ongoing conflict between Ukraine and Russia, the conflicts in the Middle East, geopolitical tensions with China, and other geopolitical events, will affect our business operations, clinical trials, or financial condition;
our expectations regarding other macroeconomic trends;
our intellectual property position, including the timingscope of protection we are able to establish and availabilitymaintain for intellectual property rights covering ELI-002, other product candidates we may develop, including the
extensions of data from suchexisting patent terms where available, the validity of intellectual property rights held by third parties, and our ability not to infringe, misappropriate or otherwise violate any third-party intellectual property rights;
our continued reliance on third parties to conduct additional clinical trials of our product candidates, and for the manufacture of our product candidates for clinical trials;
the primary endpointsour ability to be utilized in ourhave manufactured sufficient supplies of drug product for clinical trials;testing and commercialization;
the scope, progress, expansion,our ability to obtain, and costsnegotiate favorable terms of, developing and commercializingany collaboration, licensing or other arrangements that may be necessary or desirable to develop, manufacture or commercialize our product candidates;
our dependence on existing andestimates regarding expenses, future collaborators for commercializing product candidates in the collaboration;
our receipt and timing of any milestone payments or royalties under any existing or future research collaboration and license agreements or arrangements;
the potential effects of the COVID-19 pandemic on our business and operations, results of operations and financial performance;
the potential adverse effects of any regional armed conflicts on our business and operations, results of operations and financial performance;
the size and growth of the potential markets for our product candidates and the ability to serve those markets;
our expectations regarding our expenses and revenue, the sufficiency of our cash resources,capital requirements and needs for additional financing;
regulatory developments in the United States and other countries;our projected financial performance;
the rate and degree of market acceptance of any future products;
the implementation of our business model and strategic plans for our business and product candidates, including additional indications forperiod over which we may pursue;
estimate our expectations regarding competition;
existing cash and cash equivalents will be sufficient to fund our anticipated growth strategies;
the performance of third-party manufacturers;
our ability to establishplanned operating expenses and maintain development partnerships;
our expectations regarding federal, state, and foreign regulatorycapital expenditure requirements;
our ability to obtain and maintain intellectual property protection for our product candidates;
the successful development for our sales and marketing capabilities;
the hiring and retention of key scientific or management personnel; and
the anticipated trendsimpact of laws and challenges in our business and the market in which we operate.

regulations.
We caution you that the foregoing list may not contain all of the forward-looking statements made in this Annual Report on Form 10-K.

Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. We discuss many of these risks in greater detail in the “Risk Factors” and elsewheresection in Part I, Item 1A of this Annual Report on Form 10-K. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Also, forward-looking statements represent our management’s beliefs and assumptions only as of the date of this Annual Report on Form 10-K. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future.

In addition,, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based uponon information available to us as of the date of this Annual Report on Form 10-K, and while10-K. While we believe suchthat information formsprovides a reasonable basis for suchthese statements, suchthat information may be limited or incomplete, and ourincomplete. Our statements should not be read to indicate that we have conducted an exhaustive inquiry into or review of all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely uponon these statements.

This Annual Report on Form 10-K also contains estimates, projections and other information concerning our industry, our business and the markets for certain drugs, including data regarding the estimated size of those markets, their projected growth rates and the incidence of certain medical conditions. Information that is based on estimates, forecasts, projections or similar methodologies is inherently subject to uncertainties, and actual events or circumstances may differ materially from events and circumstances reflected in this information. Unless otherwise expressly stated, we obtained this industry, business, market and other data from reports, research surveys, studies and similar data prepared by third parties, industry, medical and general publications, government data and similar sources. In some cases, we do not expressly refer to the sources from which this data is derived. In that regard,
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when we refer to one or more sources of this type of data in any paragraph, you should assume that other data of this type appearing in the same paragraph is derived from the same sources, unless otherwise expressly stated or the context otherwise requires.

Trademarks

This Annual Report on Form 10-K includes trademarks, service marks and trade names owned by us or other companies. All trademarks, service marks and trade names includedAs used in this Annual Report on Form 10-K, areunless otherwise stated or the property of their respective owners.

Risk Factors Summary
The following is a summary ofcontext otherwise indicates, references to “Elicio,” the principal factors that cause an investment in the company“Company,” “we,” “our,” “us” or similar terms refer to be speculative or risky:
Risks Relating to Our Financial Position and Need for Additional Capital
We are a clinical-stage biopharmaceutical company with no products approved for sale and we have not generated any product revenue to date, which makes it difficult to assess our future viability.
To achieve our goals we will require substantial additional funding, for which capital may not be available to us on acceptable terms, or at all, and, if not so available, may require us to delay, limit, reduce or cease our clinical trials or operations.
Risks Relating to the Development and Regulatory Approval of Our Product Candidates
COVID-19 could adversely impact our business, including our clinical trials and financial condition.
Product development and regulatory approval involve a lengthy and expensive process with uncertain outcomes. We cannot be certain ANG-3070 or any of our other product candidates will receive or maintain regulatory approval and, without regulatory approval, weElicio Therapeutics, Inc. and our collaborators will not be able to market our product candidates.
Delays or difficulties in the commencement, enrollment and completion of clinical trials could result in increased costs to us and delay or limit our ability to obtain regulatory approval for ANG-3070 and our other product candidates.
Clinical failure can occur at any stage of clinical development, and the results of earlier clinical trials are not necessarily predictive of future results.
Our clinical trials could be disrupted by the uncertainty of war due to the aggressive actions taken by Russia which, if this occurs, could delay our ability to complete our clinical trials.
Even if we successfully complete ongoing and planned clinical trials of one or more of our product candidates, the product candidates may fail for other reasons.
Our product candidates may have undesirable side effects which may delay or halt clinical development or prevent marketing approval or, if approval is received, require them to be taken off the market, require them to include safety warnings, or otherwise limit their sales.
Clinical trials of our product candidates may not uncover all possible adverse effects that patients may experience or be indicative of the effect of our product candidates post approval in the general population.
Due to the significant resources required for the development and commercialization of our product candidates, we must prioritize development of certain product candidates and/or certain disease indications. We may expend our limited resources on product candidates or indications that do not yield a successful product and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.
Our business operations and current and future relationships with investigators, healthcare professionals, consultants, third-party payors, patient organizations and customers will be subject to applicable healthcare regulatory laws, which could expose us to penalties.
If manufacturers obtain approval for generic versions of our products or product candidates, our business will be materially harmed.wholly owned subsidiaries.
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Risks Relating to Collaborations and Commercialization of Our Product Candidates
If we are able to develop and obtain regulatory approval for any of our product candidates, our business will be materially harmed if we are unable to successfully commercialize such approved products.
If we fail to develop market opportunities for ANG-3070 or any future products are smaller than we believe they are, our potential to generate revenue may be adversely affected, and our business may suffer.
Risks Relating to Our Business and Strategy
We face competition from other biotechnology and pharmaceutical companies and our operating results will suffer if we fail to compete effectively.
We currently depend on single third-party suppliers for the manufacture and supply of drug substance and potential future commercial product supplies for our product candidates, and any performance failure on the part of our supplier could delay the development and potential commercialization of our product candidates.
We depend on third-party contractors for a substantial portion of our operations and may not be able to control their work as effectively as if we performed these functions ourselves. If these third parties do not successfully carry out their contractual duties or meet expected deadlines, we may be unable to obtain regulatory approval for or commercialize our product candidates, if approved.
Risks Relating to Our Intellectual Property
It is difficult and costly to protect our proprietary rights, and we may not be able to ensure their protection. If our patent position and potential regulatory exclusivity do not adequately protect our product candidates, others could compete against us more directly, which would harm our business, possibly materially.
If we do not obtain protection under the Hatch-Waxman Act and similar legislation outside of the United States by extending the patent terms and obtaining data exclusivity for our product candidates, our business may be materially harmed.
We may incur substantial costs as a result of litigation or other proceedings relating to patent and other intellectual property rights.
We may infringe the intellectual property rights of others, which may prevent or delay our product development efforts and stop us from commercializing or increase the costs of commercializing our product candidates.
Risks Relating to Our Common Stock
Our stock price may be volatile and you may not be able to resell shares of our common stock at or above the price you paid.
We identified material weaknesses in our internal control over financial reporting and we may identify additional material weaknesses in the future that may cause us to fail to meet our reporting obligations or result in material misstatements of our financial statements. If we fail to remediate any material weaknesses or if we otherwise fail to establish and maintain effective control over financial reporting, our ability to accurately and timely report our financial results could be adversely affected.
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Part I
Item 1. Business
Overview
We are a clinical-stage biopharmaceuticalbiotechnology company focused onpioneering the discovery, development and commercialization of novel small molecule therapeutics to address chronic and progressive fibrotic diseases. Our goal is to transform the treatment paradigmimmunotherapies for patients with limited treatment options and poor outcomes suffering from these potentially life-threatening conditions for which there are no approved medicines or where existing approved medicinescancer and infectious disease. Our proprietary Amphiphile (“AMP”) technology is designed to mobilize the body’s immune response by preferentially targeting our product candidates to the lymph nodes with the goal of generating a robust T cell response.Recent advances have known limitations. Our lead product candidate is ANG-3070, a highly selective oral tyrosine kinase receptor inhibitor (TKI) in developmentidentified T cell responses as a treatment for fibrotic diseases, particularly in the kidney and lung. ANG-3070 has demonstrated activity as an anti-fibrotic agent in a varietykey component of animal models. A Phase 1 healthy volunteer study, which was designed to support clinical development in multiple indications, demonstrated ANG-3070 has a favorable safety and PK profile, producing plasma concentrations which exceeded the levels necessary for activity in animal models of proteinuric kidney diseases. Enrollment is ongoing in a dose-finding Phase 2 trial of ANG-3070 in primary proteinuric kidney diseases (PPKDs)effective cancer immunotherapy and we expectbelieve our AMP technology can generate a robust T cell response that can potentially provide meaningful clinical benefit.
We believe the therapeutic utility of currently approved and development stage immunotherapies are limited in many cases due to file an IND in idiopathic pulmonary fibrosis (IPF) bytheir inability to sufficiently localize to lymph nodes and adequately engage with the endcritical immune cells responsible for stimulating adaptive immunity.Our AMP technology is specifically intended to localize payloads to lymph nodes leading to the generation of 2022.
We continue to work with our license partner Vifor International, Ltd, (Vifor Pharma) on the process of closing out our analyses of data from the 2021 clinical trial readouts of ANG-3777, a hepatocyte growth factor (HGF) mimetic that was formerly our lead product candidate until December 2021. We do not intend to continue the clinical development plan for ANG-3777 set forth in the Vifor License, which had included a Phase 3 study for the prevention of AKI in patients undergoing cardiac surgery involving cardiopulmonary bypass who were thought to be at risk for AKI (CSA-AKI) and a Phase 4 confirmatory study in donor kidney transplant patients who were at risk for developing delayed graft function (DGF), givenrobust T cell response that we do not believe the earlier Phase 2 and Phase 3 clinical trialis critical to generate an anticancer immune response.
We have developed our cancer vaccine product candidates to target biologically validated tumor mutation drivers using known neoantigens.This strategy results in the respective indications support regulatory approval. We have no funds budgeted for additional clinical trials for ANG-3777.
We are also continuingan “off-the-shelf” therapeutic option allowing patients to develop our preclinical programs. Our ROCK2 program is targeted towards thereceive treatment of fibrotic diseases. Our CYP11B2 program is targeted towards diseases relatedwithout delay due to aldosterone synthase dysregulation.
ANG-3070 for Fibrotic Diseases.manufacturing timelines and costs associated with personalized vaccine approaches.
Our lead product candidate is ANG-3070,clinical and preclinical pipeline includes the lymph node targeted therapeutic cancer vaccines ELI-002, currently being evaluated in a highly selective oral small molecule TKI we are developing asPhase 2 clinical program, designed to stimulate an immune response against mutant KRAS cancers, ELI-007, currently being evaluated in a potential treatment for fibrotic diseases. TKIs are one of the largest classes of newly approved drugs, with more than 25 approved molecules worldwide targeting pathways believed to affect relevant diseases. However, tyrosine kinases are ubiquitous proteins and there is significant overlap in their structures and binding sites. This can lead to binding against unintended tyrosine kinase targets and these off-target effects are largely responsiblepreclinical study for the toxicity associated with TKIs. While no TKI can be entirely selectivetreatment of mutant v-raf murine sarcoma viral oncogene homolog B1 (“BRAF”) -driven cancers, and ELI-008, currently being evaluated in a preclinical study for use in the treatment of mutated tumor protein p53 (“TP53”) expressing cancers.We believe that each of our cancer vaccine product candidates, if approved, have the potential to improve the lives of patients suffering from solid tumors arising due to close structural homology of the various tyrosine kinases, ANG-3070 was designed with the intent of enhancing inhibition of kinases involved in inflammation and the progression of fibrosis while minimizing binding to kinases thought responsible for adverse or off-target effects. ANG-3070 demonstrated target engagement as an anti-fibrotic agent in a variety of animal models across different organ systems and has shown in vitro the ability to inhibit pro-fibrotic tyrosine kinases at exposures achievable by oral administration. We reported positive data from a Phase 1 healthy volunteer study in August of 2021 and are actively enrolling patients in JUNIPER, a randomized, multi-center, double-blind, and placebo-controlled global dose-finding Phase 2 trial to evaluate ANG-3070 in patients with primary proteinuric kidney diseases (PPKDs). We hold global rights to ANG-3070.specific oncogenic driver mutations.
The potential advantages for ANG-3070 include:
Significant Addressable Kidney Fibrosis Markets. The PPKDs of Focal Segmental Glomerular Sclerosis (FSGS), Immunoglobulin A Nephropathy (IgAN), Alport Syndrome, and Membranous Nephropathy (MN) together affect over 250,000 patients in the U.S. alone.
Significant Addressable Pulmonary Fibrosis Markets. 2021 projected worldwide sales for the two approved drugs for IPF will be approximately $3.8 billion despite the fact that fewer than 30% of IPF patients in the U.S. are prescribed either drug and approximately half of IPF patients discontinue these therapies within 12 months.
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Promising Drug Exposure Profile. In the Phase 1 healthy volunteer study, ANG-3070 demonstrated ANG-3070 can achieve drug exposures exceeding plasma concentrations in which activity was demonstrated in animal models of proteinuric kidney diseases and pulmonary fibrosis.As such, ANG-3070 is being investigated for both twice-daily (BID) and once-daily (QD) dosing.
Encouraging Adverse Event Profile. The safety and tolerability profile in the Phase 1 study was encouraging given the recognized incidence and severity of gastrointestinal side effects in approved kinase inhibitors, particularly nausea, vomiting, and diarrhea.
ANG-3070 for Renal Fibrosis. While PPKDs like FSGS, IgAN, MN, and Alport often have different root causes, each condition often progresses to kidney fibrosis and end-stage renal disease. There is only one approved therapy for any PPKD, budesonide for IgAN. In December 2021, we enrolled the first patient into JUNIPER, our randomized, double-blind, placebo-controlled global dose-finding Phase 2 trial intended to assess ANG-3070 in adult patients with FSGS or IgAN, two types of PPKD.
ANG-3070 for Pulmonary Fibrosis. Pulmonary fibrosis is characterized by progressive scarring (fibrosis) of the lungs, which leads to their deterioration and destruction. Over time, lung scarring in patients progresses and breathing becomes difficult, often resulting in the lungs failing to take in enough oxygen to meet the body’s needs. IPF is an aggressive form of lung disease with a median survival of two to three years from diagnosis. There are two drugs approved for IPF, the kinase inhibitor nintedanib (OFEV®) and the pyridine pirfenidone (Esbriet®). We plan to file an IND for ANG-3070 in the IPF indication by the end of 2022.
ANG-3777, an HGF Mimetic for Acute Organ Injury
ANG-3777 was designed to mimic the biological activity of HGF and to treat acute organ injuries, such as delayed graft function, where there are no approved therapies. HGF activates the c-Met receptor, which triggers a cascade of pathways with a central role in tissue repair and organ recovery that has been well established.
In the fourth quarter of 2021, we reported topline results from two clinical trials of ANG-3777. The first was a Phase 3 trial of ANG-3777 to treat AKI in patients who were at risk for developing DGF. The second was an exploratory Phase 2 trial for the prevention of CSA-AKI. While neither trial achieved statistical significance on its primary endpoint, we believe ANG-3777 demonstrated biologic activity in both trials. We continue to work with our license partner Vifor International, Ltd. (Vifor Pharma) on the process of closing out our analyses of data from these trials. We do not intend to continue the clinical development plan for ANG-3777 set forth in the Vifor License, which had included a Phase 3 study in CSA-AKI and a Phase 4 confirmatory study in DGF. There are no funds budgeted for additional clinical trials for ANG-3777.
In November 2020, we entered into a license agreement (the Vifor License) with Vifor Pharma, granting Vifor Pharma global rights (excluding Greater China) to develop, manufacture and commercialize ANG-3777 in all therapeutic, prophylactic and diagnostic uses for renal indications, including forms of AKI, and congestive heart failure (collectively, the Renal Indications). Pursuant to the Vifor License, we received an upfront license payment of $30 million in November 2020, and a $30 million equity investment, $5 million of which we received in January 2021 and $25 million of which we received contemporaneously with the closing of our Initial Public offering (IPO). Although the Vifor License includes additional milestone and royalty objectives, we do not expect to receive any clinical, post-approval, or sales milestones, or royalties, as we do not intend to continue to pursue the clinical development plan set forth in the Vifor License. In 2022, we and Vifor Pharma continue to complete planned analyses of the results of the clinical trials announced in the fourth quarter of 2021 and discuss the future of the collaboration on the basis of such analyses.
Our Preclinical Pipeline
We have a wholly-owned preclinical pipeline of internally-developed programs, including a ROCK2 inhibitors programs for fibrotic diseases, and CYP11B2 inhibitor program. Our goal is to select clinical lead candidates for one or more of these programs and begin IND-enabling studies by the end of 2022.
ROCK2 Inhibitors for Fibrotic Diseases. Our ROCK2 program includes a number of highly selective, oral small molecule inhibitors of ROCK2 developed internally as a potential treatment for fibrotic and other diseases. Rho-associated coiled-coil forming protein kinase (ROCK) signal transduction pathways are implicated in the development of fibrosis. Inhibition of ROCK isoforms ROCK1 and ROCK2 has shown promise in fibrosis and dual
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ROCK1/ROCK2 inhibitors have been used to treat conditions including hemorrhagic stroke and glaucoma. However, ROCK1 inhibition has been associated with hypotension (low blood pressure) and enhanced vascular permeability. Recent scientific work using specific genetic or pharmacological reduction of ROCK2 indicates ROCK2 inhibition by itself can result in anti-fibrotic activity without causing hypotension. These findings informed our strategy to develop a ROCK2-specific inhibitor, with the goal of minimizing ROCK1 inhibition, as a potential treatment for fibrosis and other diseases. We believe this approach could translate into a product candidate with enhanced tolerability potentially supporting long-term systemic use. We hold global rights to our ROCK2 inhibitor program.

CYP11B2 Inhibitors. We have created a selection of molecules with high specificity to CYP11B2 (aldosterone synthase) relative to CYP11B1, which we are investigating for the purpose of targeting aldosterone-related diseases, which include resistant hypertension, congestive heart failure, renal fibrosis and primary hyperaldosteronism. We hold global rights to our CYP11B2 inhibitor program.
Commercialization
Our lead product candidate, ANG-3070, is a highly selective, oral small molecule TKI we are developing as a potential treatment for fibrotic diseases, particularly of the kidney and lung. We reported positive data from a Phase 1 healthy volunteer study in August of 2021 and have enrolled the first patients in JUNIPER, a randomized, multi-center, double-blind, and placebo-controlled global dose-finding Phase 2 trial to evaluate ANG-3070 in patients with primary proteinuric kidney diseases (PPKDs). We hold global rights to ANG-3070, including all commercial rights. As we advance the program, we will evaluate how to successfully commercialize ANG-3070. We do not intend to continue the clinical development plan for ANG-3777 set forth in the Vifor License, which had included a Phase 3 study in CSA-AKI and a Phase 4 confirmatory study in DGF.
Management
Our pipeline and company strategy were originated and are supported by a management team with extensive experience and expertise in clinical research and development, business development, and commercialization. Our President and Chief Executive Officer, Jay Venkatesan, M.D., was the founder and CEO of Alpine BioSciences (acquired by Cascadian Therapeutics, which was subsequently acquired by Seagen), was a key investor in Mavupharma Inc. (acquired by AbbVie), and is a former portfolio manager of Ayer Capital and director of Brookside Capital Partners (the hedge fund group affiliated with Bain Capital). Our Chief Medical Officer and Head of Research, John F. Neylan, M.D., is a nephrologist who has held leadership roles at Keryx Biopharmaceuticals, Genzyme Corporation, and Wyeth Corporation. Our Chief Business Officer and General Counsel, Jennifer J. Rhodes, has held leadership roles at Pfizer Inc., Medivation Inc., and Adamas Pharmaceuticals, Inc. These individuals and other members of our senior management team have contributed to the clinical development, registration and/or commercialization of a multitude of approved drug products.
Company History
We were founded in 1998. From our incorporation through 2014, our efforts were primarily focused on researching pathways related to serious organ diseases and applying our medicinal chemistry expertise towards creating potential therapeutics to address the unmet medical needs of patients. Since 2014, we have focused on the clinical development of our ANG-3070 and ANG-3777 programs and translational work necessary to bring our pipeline programs to the clinic. ANG-3070 is now our lead clinical asset.

Our corporate operations are based in San Francisco, California, our clinical development and regulatory teams are primarily located in Boston, Massachusetts, and our discovery and research programs are based in Uniondale, New York.
Our Strategy
We are focused on discovering,mobilizing the immune response to defeat cancer and infectious diseases through the development and commercialization of lymph node targeted immunotherapies. Key elements of our strategy are to:
Continue advancing ELI-002 through the ongoing randomized Phase 2 trial in pancreatic ductal adenocarcinoma (“PDAC”).We are initially developing our first product candidate, ELI-002, for the treatment of patients with solid tumors carrying mutated KRAS. By targeting immunotherapy to the lymph nodes and commercializing novel small molecule therapeuticsgenerating a robust and differentiated T cell response, we believe ELI-002 could improve the long-term prognosis and quality of life for patients suffering from solid tumors. We are currently conducting AMPLIFY-7P, a randomized Phase 2 trial to address fibrotic diseases, particularlyevaluate the efficacy and safety of ELI-002 in patients with PDAC.
Expand ELI-002 clinical development for the treatment of other KRAS driven cancers.Our ongoing Phase 2 trial is in PDAC, but our Phase 1 trials included patients with colorectal cancer and the preliminary safety, immunogenicity and efficacy data were encouraging in both PDAC and CRC patients.In addition to CRC, there are large groups of patients with lung cancer, bile duct and other gastrointestinal cancers driven by KRAS mutations.We are evaluating opportunities to advance ELI-002 in clinical trials for CRC including in collaboration with other organizations.
Advance development of our internal pipeline for additional oncology targets. We have two preclinical programs that employ our AMP technology targeting other key tumor driver mutations, BRAF and TP53.ELI-007, for mutant BRAF-driven cancers, and ELI-008 for mutant TP53-expressing cancers, are AMP immunotherapies targeting biologically validated neoantigens expressed in high proportions of solid tumors.We have received grants to fund the preclinical development of ELI-007 and ELI-008 and will continue to seek collaboration opportunities to advance their development.
Realize the full value of the kidneyAMP technology through collaborations. We and lung. Our goal isothers have published several preclinical proof-of-concept applications where our AMP technology has demonstrated meaningful improvements when applied to transform the treatment paradigm for patientsprophylactic or therapeutic vaccines, CAR-T and TCR-T cell therapies, and
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suffering fromtherapies for auto-immune disease.We will look to form collaborations to capitalize on the potential of the technology in these potentially life-threatening conditions for which there are no approved medicines or where existing approved medicines have recognized limitations. The key tenetsapplications.
Overview of our business strategy are to:Immune System and Cancer Immunotherapy
Develop ANG-3070 in multiple renal fibrosis indications. We believe ANG-3070 can addressThe immune system is a large unmet medical neednetwork of organs, tissues, white blood cells, proteins and chemicals working together to protect and repair the body from infections, injuries and cellular changes that can result in patients with PPKDs progressing towards renal fibrosisdisease.One component of the immune system is the adaptive immune response which is responsible for mounting highly specific responses to substances deemed to be foreign.The adaptive immune response is carried out by white blood cells including B lymphocytes and end-stage renal disease. WeT lymphocytes. B lymphocytes (“B cells”) are currently enrolling JUNIPER, a global Phase 2 trial of ANG-3070. JUNIPER is a randomized, double-blind, placebo-controlled dose-finding trial intended to assess ANG-3070 in adult patients with FSGS or IgAN, two types of PPKDs. The trial will enroll 100 patients equally among four treatment arms: 200mg ANG-3070 once daily, 400mg ANG-3070 once daily, 300mg ANG-3070 twice daily, and placebo with dosing for 12 weeks. The primary endpointinvolved in the study is the percentage reduction in urinary protein/creatinine ratio (UPCR) at week 12. Topline data from this trial should be availablehumoral immune response, differentiating into antibody-secreting plasma cells on activation and recognition of a foreign-specific molecular structure known as an antigen. T lymphocytes (“T cells”) participate primarily in the first halfcell-mediated immune response and are capable of 2023.
specific antigen-directed recognition and elimination of aberrant cells arising from pathogenic infection or genetic transformation.Develop ANG-3070T cells can be further segregated into distinct cell types, with the primary types being CD8+ T cells, which are also referred to as cytotoxic lymphocytes (“CTLs”) and CD4+ “helper” T cells. CD8+ T cells specifically recognize and eliminate cells infected with viruses, other pathogens, or cancer-associated mutations. In contrast, CD4+ T cells, which can also exhibit cytotoxic activity, primarily participate in Idiopathic Pulmonary Fibrosis. Given multiple animal models demonstratingthe immune response by directing the activity of ANG-3070 activityother cells, in pulmonary fibrosis, we intend to complete IND-enabling workparticular B cells and file an IND by the end of 2022 for a Phase 2 trial of ANG-3070 in IPF, a chronic, life-threatening condition. There are two medicines currently approved for IPF by regulators, pirfenidone and nintedanib. However, we believe additional therapies are needed to treat IPF, since approximately half of IPF patients discontinue taking these approved medicines within one year. Fewer than one-third of IPF patients are currently prescribed pirfenidone or nintedanib. Despite this, the two medicines together are projected to sell $3.8 billion worldwide in 2021.CD8+ T cells.
The lymphatic system plays a major role in the production, differentiation, and proliferation of both B cells and T cells, and lymph nodes serve a critical role in lymphocytes’ activation and acquisition of essential functionality. The lymph nodes act as the “school house” of the adaptive immune response playing an essential role in the generation of B cells and T cells possessing the specificity and functionality required for effective disease modification.AdvancementSpecifically, signaling delivered between immune cells residing in the lymph nodes is critical for the generation of our earlier-stage programs. a T cell response with the magnitude, potency, persistence, functionality, specificity, and memory capacity required for an effective cell-mediated immune response.
As cancer is the result of genetic transformation of normal cells resulting in uncontrolled growth, the immune system doesn’t always recognize cancer cells as foreign.Our ROCK2 inhibitor programIn addition, cancer cells can adopt mechanisms to evade immune system recognition or defenses rendering the adaptive immune response ineffective.However, researchers have found that immune cells, referred to as tumor-infiltrating lymphocytes (“TILs”), are sometimes found in and around tumors and patients with TILs often have a better prognosis than patients without TILs.Following this observation, immunotherapy has been envisioned as a treatment approach intended to enhance the ability of the immune system to eliminate disease including cancer.
In the last few decades, immunotherapy has become an important part of treating certain cancers.Several approaches to cancer immunotherapy have been attempted all with the goal of eliciting or enhancing an immune response to identify and attack tumor cells.One immunotherapy approach attempted with limited success to date is the development of therapeutic cancer vaccines.Cancer cells often contain tumor-specific antigens, or neoantigens, not present in normal cells that could facilitate the immune system recognition and response to these neoantigens and ultimately, elimination of the cancer cells.In addition, because an adaptive immune response includes a mechanism to create life-long lymphocytes, cancer vaccines may prevent relapse of cancer long after initial treatment.
While general neoantigen-specific immune activity has been demonstrated by previous cancer vaccine efforts, reduction in tumor loads has not been frequently observed resulting in only two FDA-approved cancer vaccines. Researchers investigating this lack of historical cancer vaccine efficacy have suggested a key reason is the limited generation of tumor-specific T cells as well as impaired fitness of the elicited anti-tumor T cells.
We believe improved delivery of immunotherapies to the lymph nodes is required to generate the robust and multifunctional adaptive immune response, specifically T cell responses, needed for therapeutic efficacy. Elicio’s AMP technology is designed to advance a potent and highly selective inhibitordeliver therapeutic payloads of ROCK2, with minimal inhibition of ROCK1, which we believe could translate into a therapeutic with enhanced tolerability in patients with fibrotic diseases. We are also developing proprietary CYP11B2 inhibitors for the purpose of targeting aldosterone-related diseases. We expectinterest to nominate a lead compound and initiate IND-enabling studies for at least one of these earlier-stage programs by the end of 2022.lymph nodes.
Our Pipeline
Our research and development activities are primarily focused on discovering and investigating novel small molecule therapeutics to address fibrotic diseases. All our pipeline programs were developed internally and are wholly owned by Angion. Anticipated milestones are reflected in the chart below:
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ANG-3070, Our Lead Product CandidateApproach
Our lead product candidate, ANG-3070,The fundamental underpinning of our innovative approach to induce an immune response capable of meaningful clinical benefit is a highly selective, oral small molecule TKI developed internally as a potential treatment for fibrotic diseases, particularly in the kidney and lung. ANG-3070 has demonstrated positive results in a Phase 1 healthy volunteer study, proof of concept in a variety of animal models as an anti-fibrotic agent, and the ability in vitro delivering payloads to inhibit pro-fibrosis tyrosine kinases at levels achievable with oral administration.
Within fibrosis, we believe there is promising therapeutic potential for ANG 3070 in PPKDs, a group of kidney diseases characterized by excess urinary protein excretion, and in types of pulmonary fibrosis, particularly IPF.lymph nodes. In August 2021, we reported positive final data on a Phase 1 studyOur AMP technology is designed to rapidly deliver peptides, proteins, nucleic acids and small molecules to lymph nodes through reversible interactions with endogenous albumin.Our AMP technology has been flexibly designed to be manufactured with various peptide lengths and sequences optimizing the localization of ANG-3070 in healthy volunteers. In December 2021 we enrolled the first patient in “JUNIPER”, a randomized, multi-center, double-blind,AMP-modified molecules to lymph nodes and placebo-controlledthe subsequent cellular processing required to generate robust T cell response.
AMP Technology: Lymph node targeting via albumin hitchhiking
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global dose-finding Phase 2 studyOur proprietary AMP technology, and combined expertise in PPKD patients focused on FSGSimmunology and IgAN. We planmaterials science allows us to file an INDdevelop AMP immunotherapies capable of generating robust and differentiated immune responses.Our AMP immunotherapies utilize modular conjugation chemistry, potentially allowing for ANG-3070 in IPF by the end of 2022.

Fibrotic Diseasesapplication to multiple therapeutic modalities, including peptides, proteins, nucleic acids, and Tyrosine Kinase Inhibitors
Fibrosis is a part of the body’s natural healing response to organ injury. When it becomes dysregulated, fibrosis can be highly detrimental to a normal organ’s architecture and function, potentially leading to death from organ failure. Two major organs commonly impacted by fibrosis are the kidney and the lung.
Renal or kidney fibrosis is the underlying pathological process leading to progression of chronic kidney disease (CKD), a disease affecting more than 10% of the world’s population, and renal fibrosis is currently also the best predictor of disease progression. No specific anti-fibrotic therapeutics currently exist to combat renal fibrosis.
Pulmonary or lung fibrosis is a disease which occurs when lung tissue becomes damaged or scarred. The resulting thickened, stiff tissue makes it more difficult for lungs to work properly. As pulmonary fibrosis worsens, patients have progressive shortness of breath and face increasing restrictions on activities of daily living. Pulmonary fibrosis is a family of over 200 different diseases, including IPF. At this time, pulmonary fibrosis is not reversible and remains a terminal disease.
TKIs are known to affect a wide array of biochemical pathways, including the mediation of tissue inflammation and fibrosis. TKIs are one of the largest classes of newly approved drugs, with more than 25 approvedsmall molecules worldwide targeting pathways believed to affect relevant diseases. However, tyrosine kinases are ubiquitous proteins and there is significant overlap in their structures and binding sites. This can lead to binding against unintended tyrosine kinase targets and these off-target effects are largely responsible for the toxicity associated with TKIs.
ANG-3070 was designed with the intent of having enhanced inhibition of kinases involved in inflammation and the progression of fibrosis while minimizing binding to kinases thought responsible for adverse or off-target effects. Four kinase receptors targeted by ANG-3070 include platelet-derived growth factor receptor alpha and beta (PDGFRα and PDGFRβ, respectively) and Discoidin Domain Receptors 1 and 2 (DDR1 and DDR2). ANG-3070 has demonstrated potent, low nanomolar IC50s (a standard measure of drug potency) to these tyrosine kinase receptors as shownillustrated in the figure below. PDGFRα, PDGFRβ, DDR1, and DDR2below:
AMP construction: A molecular conjugation approach for
delivery of immune therapeutics to lymph nodes
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AMP molecules are implicated in a number of diseases and targeting them effectively could providemultifunctional constructs with lipid tails linked to a therapeutic benefitpayload designed to patientsaccumulate in the lymph nodes through the body’s existing surveillance mechanisms.AMP molecules are designed to interact with renalendogenous albumin, an abundant protein present in tissues that drains through lymphatic capillaries and pulmonary fibrosis.accumulates in lymph nodes where foreign substances are collected for risk-assessment by sentinel immune cells.
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PDGFRαAMP molecules use their lipid tails to target the lymph nodes by hitchhiking on endogenous albumin after subcutaneous injection resulting in precise delivery to immune cells responsible for coordinating protective immune responses.Albumin hitchhiking is a well-established method for targeting molecules to lymph nodes. Our AMP technology preferentially traffics immuno-modulatory molecules to lymph nodes enhancing the magnitude, potency, functionality, and PDGFRβ are expressed in renal mesenchymal cells (i.e., glomerular mesangial cells) or cells with stem-cell like properties capable of maturing into a variety of critical cell types and in vascular smooth-muscle cells. In addition, they are expressed in interstitial cortical fibroblasts forming the skeletondurability of the kidney and medullary pericytes responsible for blood flow throughimmune response. We believe this lymph node-targeting technology has the kidneys. In human renal disease, PDGFRα is upregulated in glomerulus as well as arterial smooth muscle cells and endothelial cells. Activation of PDGFRβpotential to be broadly applicable to address significant unmet medical needs.
AMP Facilitated Albumin Hitchhiking
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specificallyTargeting Common Validated Tumor Neoantigens
We believe a critical strategic benefit of our approach is utilizing common neoantigens that when combined with the AMP-modification could generate an effective T cell-mediated anti-tumor response.Common neoantigens represent an elite class of tumor-specific antigens derived from recurrently mutated driver genes shared across certain types of cancer.Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation or dysregulated protein synthesis. Neoantigens are recognized as non-self and can readily trigger an immune response.
Our most advanced clinical product candidate is a cancer vaccine that targets the tumor driver gene KRAS, which is mutated in renal mesenchymalmore than 25% of all solid tumors.Our preclinical cancer vaccine candidates target two other key neoantigens TP53, the most commonly mutated cancer driver gene, and BRAF, a cancer driver gene found frequently in melanoma, thyroid, and colon cancers.
Utilizing potent adjuvants
In addition to utilizing well-known neoantigens we incorporate potent adjuvants as our AMP immunotherapy’s rapid localization to the lymph nodes supports enhanced delivery to immune cells is sufficientpotentially resulting in higher,more robust immune responses with potentially fewer side effects.Adjuvants are any substance included in an immunotherapy intended to induceactivate immune cells to elicit a stronger immune response.Our current product candidates utilize a synthetic oligodeoxynucleotides adjuvant, CpG 7909, intended to mimic bacterial DNA that has been extensively studied and drive progressive glomerulosclerosis and interstitial renal fibrosis. Being able to downregulate or prevent these targets could be beneficial to patients with related renal diseases.incorporated into FDA-approved products.
In patients with early, but not late stage, IPF, cells responsible forprevious clinical studies conducted by third parties, CpG-containing oligonucleotides have been shown to be both well tolerated and to exert immune-stimulatory effects. Our AMP-modification is designed to concentrate and retain the ability of the lung to exchange oxygen, cells lining the inside of blood vessels, and fibroblasts making up the structure of the lung express increased PDGFRβ. PDGFRα is expressed in these same cells in IPF patients, plus in lung immune cells. During pulmonary fibrosis, both PDGFRα and PDGFRβ are involved in pro-fibrotic activity, suggesting a therapy specific to these targets might exert beneficial anti-fibrotic effects for patients with IPF.
DDR1 is a tyrosine kinase transmembrane receptor of collagens, expressed in several cell types and organs, including the gastrointestinal tract, brain, lung, mammary gland, and kidney. Despite collagen being the most abundant proteinCpG adjuvant in the body, DDR1 is not induced lymphatic system potentially allowing more effective delivery to immune cells and/or activated under normal conditions. Several studies show DDR1 is overexpressed in pathological conditions and participates in tissue adaptation to acute and chronic inflammatory lesions, including renal inflammation and fibrosis. In a mouse model of Alport’s Syndrome (AS), for example, deletion of DDR1 delays renal fibrosis. Other animal studies suggest DDR1 could play an important role in IPF, mediating the creation of permanent pulmonary surface cell lesions. Targeting DDR1 with an effective therapeutic would help reduce some of the adverse effects related to DDR1 activation, potentially helping patients with DDR1-related diseases.
In contrast to DDR1’s primary expression in epithelial cells and activation by multiple types of collagens, DDR2 is abundantly expressed in fibroblasts. In the early phase of fibrosis in IPF, TGF-β induces expression of DDR2 in lung fibroblasts and synergizes with the resulting downstream signals to accelerate formation of fibrotic tissue. In later stages of fibrosis with the fibrotic process is already established, the DDR2/ERK axis promotes the oversynthesis of extracellular matrix components, resulting in massive fibrosis. Given these roles in pro-fibrotic pathways, targeting DDR2 could help prevent or reduce fibrosis in patients with chronic fibrotic disease.reduced side effects.

Disease Overviews and Markets
Our lead product candidate, ANG-3070,The result of our approach is a highly selective, oral small molecule TKI developed internally as a potential treatment for renal and pulmonary fibrosis. In December 2021, we enrolled the first patient in “JUNIPER” a randomized, multi-center, double-blind, and placebo-controlled global dose-finding Phase 2 study in PPKD patients with FSGS and IgAN. We plan to file an IND for ANG-3070 in IPF at the end of 2022.

Primary Proteinuric Kidney Disease (PPKD)
A common thread among certain kidney diseases is the presence of abnormal levels of protein in the urine, or proteinuria. This is an indication of damaged kidneys and the presence of potentially serious disease. PPKDs share proteinuria as the common primary means of diagnosis.
Despite the differences in root causes among various PPKDs, they have a common path of disease progression as seen in the figure below. PPKDs typically move from proteinuria, through the development of fibrosis, chronic kidney disease, and eventually to end-stage renal disease and kidney failuretherapeutic cancer vaccines targeting common tumor neoantigens found in a significant portion of patients with cancer.Our AMP immunotherapies are manufactured through traditional pharmaceutical methods resulting in transplantation or death. Therefore, wean “off-the-shelf” drug product.  
Our Product Candidates
ELI-002: AMP Immunotherapy for mutant KRAS-driven Cancers
ELI-002 is a multivalent lymph node–targeted AMP peptide vaccine being developed to target seven KRAS driver mutations that are developing ANG-3070 to address the fibrosis experienced by PPKD patients regardlesspresent in 25% of all solid tumor cancers including 88% of PDAC, 36% of colorectal cancer (“CRC”), and 25% of non-small cell lung cancer (“NSCLC”). Other cancers with significant proportions of KRAS mutations include bile duct and ovarian cancers. The KRAS protein relays signals from outside of the root etiologycell membrane to the cell nucleus influencing expression of their specific condition.
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Four types of PPKDs include IgA nephropathy, Alport Syndrome, Focal Segmental Glomerulosclerosis, and Membranous Nephropathy.
Focal Segmental Glomerulosclerosis (FSGS) is a rare form of nephrotic disease (disease in which kidney damage allows proteins to leak into the urine) in which scar tissue developsdownstream genes involved in the glomeruli,regulation of cell growth, cell differentiation, and cell death (also referred to as apoptosis). Mutations to the structuresKRAS gene result in expression of overactive KRAS protein, driving aberrant signaling and unregulated cell growth, which are hallmarks of cancer.
Targeting mutated KRAS using immunotherapy presents several potential advantages. KRAS mutations are categorized as truncal mutations serving as a genetic driver of malignant changes where each tumor cell must maintain the kidneys responsible for filtering wasteexpression of the mutated KRAS protein to remain viable. Such uniform expression across every transformed cell in a particular tumor holds the promise that immunological approaches may enable complete tumor eradication. Mutated KRAS proteins are neoantigens, found exclusively in tumor cells, potentially limiting immunotherapy activity to the targeted tumor cells limiting side effects. ELI-002 is chemically synthesized with traditional manufacturing methods that allow the drug product to be readily available as an “off-the-shelf” treatment providing potential cost and time-to-treatment advantages compared to personalized vaccine or cell-therapy treatments.
ELI-002 Preclinical Data
Preclinical studies of ELI-002 highlighted the therapeutic potential of the AMP platform and supported ELI-002’s advancement into clinical trials. Data from the blood. FSGS accounts for about 40% of adults with nephrotic syndrome and about 20% of children with nephrotic syndrome. In many cases, the cause of FSGS is unknown (idiopathic). In other cases, the scarring may occur because of another condition such as HIV infection, sickle cell disease, obesity, autoimmune diseases, or genetic causes. It is estimated that FSGS affects up to 40,000 patients in the United States, with a similar prevalence in Europe. More than 5,400 patients in the United States are diagnosed with FSGS every year, a number likely underestimated because of the limited number of biopsies performed to confirm the diagnosis. The disease adversely affects those of African descent more than other demographics. Current treatments for FSGS, corticosteroids and immunosuppressive drugs, are effective only in 25% to 35% of patients. Both of these therapeutic options were developed decades ago for non-renal indications and have been repurposed for FSGS given no approved therapy currently exists for this indication.
IgA nephropathy (IgAN) is the most common glomerulonephritis (GN, the inflammation of the cells in the kidney responsible for filtering the blood) globally and is responsible for between 10% and 20% of all GN in the United States. The prevalence in estimated at up to 150,000 in the United States. IgAN is caused by deposits of immunoglobulin A in the glomeruli caused by aberrant glycosylation, thereby disrupting renal function and causing blood in the urine (hematuria) and proteinuria. IgAN progresses steadily over time, with approximately 30% to 40% of patients developing ESRD over 20 to 30 years, including 20% of children who develop ESRD within 20 years of diagnosis. In 2021, the FDA granted accelerated approval for budesonide, a type of corticosteroid addressing the inflammatory component of IgAN, for IgAN patients based upon a percentage reduction in protein to creatinine ratio at nine months.
Membranous Nephropathy (MN) occurs when the glomeruli become damaged or thickened resulting in proteinuria. MN is often caused by some type of autoimmune activity. As protein leakage increases, so does the risk of long-term kidney damage. In the U.S., it is estimated around 3,000 patients per year will be diagnosed with MN, with an estimated prevalence of under 40,000. There are currently no approved drugs for MN.
Alport Syndrome (AS) is a genetic renal disease and is the second most common inherited cause of kidney failure. AS affects approximately 30,000 to 60,000 people in the United States. AS is caused by a genetic defect in type IV collagen, a component of the glomerular basement membrane in the kidney, resulting in defects in its structure and function. In some patients with inherited AS, the disease can progress very rapidly leading to kidney failure in early adulthood. As in other forms of PPKD, progressive fibrosis plays an important role in the pathophysiology and progression of AS. With no currently approved therapies to stop progressive loss of kidney function, AS represents a rare disorder with significant unmet need.

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Pulmonary Fibrosis
Pulmonary fibrosis is characterized by progressive scarring (fibrosis) of the lungs, which leads to their deterioration and destruction. Over time, patients’ lung scarring progresses and breathing becomes difficult, often resulting in the lungs failing to take in enough oxygen to meet the body’s needs.
IPF is an aggressive form of pulmonary fibrosis with a median survival of two to three years from diagnosis. The course of the disease is highly variable. Certain patients become seriously ill within a few months, while others may survive for five years or longer. Most deaths in IPF occur from progression of pulmonary fibrosis leading to respiratory failure. According to the NIH, approximately 140,000 people in the United States have IPF, and approximately 30,000 to 40,000 new cases are diagnosed each year, usually affecting people between the ages of 50 to 70. EU incidence rates are estimated to be similar. Over half are undiagnosed in the mild category alone, while more could be underdiagnosed. The disease is of unknown cause and represents an important area of unmet medical need.
Systemic sclerosis with interstitial lung disease is a complex immune disorder characterized by progressive pulmonary fibrosis. Systemic sclerosis (SSc), also known as scleroderma, is caused by dysfunctional interplay between fibrosis, vascular, and immunological pathways. Interstitial lung disease (ILD) is a common complication of systemic sclerosis and is its leading cause of morbidity and mortality accounting for 35% of disease specific mortality. SSc-ILD usually develops within the first five years of the disease, with 30-40% of SSc patients developing
clinically significant SSc-ILD. The U.S. prevalence of SSc-ILD is estimated to be over 60,000 with about 9,000 diagnosed each year.
There are currently two approved therapies for IPF, pirfenidone (Esbriet®, sold by Roche/Genentech) and the kinase inhibitor nintedanib (OFEV®, sold by Boehringer-Ingelheim). Nintedanib is also approved for SSc-ILD patients. Both drugs have known tolerability challenges for patients. Diarrhea and nausea are very common side effects, with 62% of patients taking nintedanib reporting diarrhea and 29% reporting nausea according to its drug label. Similarly, diarrhea was reported by 26% and nausea by 36% of patients taking pirfenidone according to its label. Patient convenience is also a recognized challenge, with nintedanib required to be dosed twice per day with food and pirfenidone three times per day with food after a three-step titration over the first two weeks. Patient drop-out rates for both drugs are substantial, with 43.8% of patients on nintedanib and 51.5% of patients on pirfenidone dropping out after 12 months. Neither therapy demonstrated an impact on patient survival in the clinical trials forming the basis for their approval. Due to the recognized limitations of these approved medicines, under 30% of U.S. patients diagnosed with IPF, despite it being a life threatening disease, are prescribed nintedanib or pirfenidone.
Despite these drawbacks to tolerability, convenience, and efficacy, pirfenidone and nintedanib generated approximately $3.8 billion in combined 2021 worldwide sales. If we are able to demonstrate in clinical trials ANG-3070 provides IPF patients with an alternative treatment option with a more acceptable tolerability, convenience, and/or efficacy profile, we would expect ANG-3070, if approved, to compete successfully with these two approved medicines. However, there is no guarantee ANG-3070 will be able to achieve these goals or, if it does, generate comparable revenues.

Our Solution: ANG-3070 for the Treatment of Renal and Pulmonary Fibrosis
By targeting tyrosine kinases receptors involved in fibrogenesis such as PDGFRα, PDGFRβ, DDR1, and DDR2, ANG-3070 could be an important potential therapeutic addressing a number of fibrotic conditions in the kidney and lung.
In August 2021, we reported positive final data from a Phase 1 study of ANG-3070 in healthy volunteers. Key findings from the study included:preclinical studies demonstrated:
ANG-3070 achieved drug exposures in humans exceeding exposures in which activity was demonstrated in animal modelsAMP-modified CpG induced significantly higher frequencies of proteinuric kidney diseasesactivated immune cells within the lymph nodes compared to soluble CpG.
Encouraging safety and tolerability profile, particularly givenAMP-modified peptide sequences generated 40x – 400x increased immune response compared to non-modified peptide sequences suggesting localizing peptides in the well-recognized incidence and severity of gastrointestinal side effects in approved TKIslymph nodes produce a robust immune response.
Pharmacokinetic data supportive of potential once-daily oral dosing for ANG-3070mKRAS-specific T cells were polyfunctional and able to elicit a cytotoxic response.
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As represented in the figure below, in Part A, healthy volunteers were given ascending single doses of ANG-3070 ranging from 50 mg to 600 mg to assess the safety, tolerability, pharmacokinetics and food effect of ANG-3070 at different doses. In Part B, healthy volunteers were given either twice-daily doses ranging from 50 mg to 500 mg under fasting conditions over two weeks or once-per-day doses ranging of 400 mg and 600 mg with meals over two weeks.
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ANG-3070 was generally well-tolerated at all doses and there were no Serious Adverse Events reported at any dose schedule or level. The reported (non-serious) Adverse Events (AEs) were seen mostly at higher doses, 600 mg administered once daily and 500 mg administered twice daily over two weeks. These AEs included nausea, abdominal cramps, and diarrhea. Generally, these AEs were mild to moderate.
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Pharmacokinetic highlights from the Phase 1 study included:
ANG-3070 was rapidly absorbed within 1-2 hours under fasting conditions;
Dosing with food delayed absorption to 3-4 hours with no change in exposure but lower incidence of nausea when given with food;
Mean half-life (T1/2) of 15-21 hours and small/no accumulation in blood after 14 days supports either once or twice per day dosing; and
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Urinary excretion less than 3%, suggestingEscalating doses of ELI-002 induced dose-dependent and consistent immune responses targeting all seven mKRAS epitopes.

AMP therapy induces strong immune responses targeting seven common KRAS mutations
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AMPLIFY-201: Our First-in-human Phase 1 trial (NCT04853017)
In October 2021, we initiated dosing of the 2-peptide version of ELI-002 in a Phase 1 study of AMP-CpG 7909 dose reductionescalation study intended to evaluate the safety and tolerability of ELI-002, as well as provide immunologic and anti-tumor proof of concept in patients with kidney disease may not be requiredhigh relapse risk mKRAS-driven solid tumors, following surgery and chemotherapy. In April 2023, we completed enrollment of 25 patients with PDAC or CRC and will continue to follow patients for up to 30 months. Results published in Nature Medicine in January 2024 from a September 6, 2023 data cutoff demonstrated:
An important finding from the Phase 1 study was human exposure levels as measured by AUC between 0-24 hours after dosing exceeded active exposure levels seen in the preclinical animal studies of ANG-3070. The figure below compares exposure levels in the passive Heymann’s nephritis rat model of MNELI-002 2P is generally well-tolerated with the exposure levels seen in the Phase 1 study. The blue box indicates theno dose range where ANG-3070 was demonstrated to be active in the MN rat model. The pair of bars on the left side notes a 15 mg/kg dose in rats provided equivalent drug exposure to 3 mg/kglimiting toxicities or about 200 mg once daily dose in humans. The next set of bars to the right show the upper endserious adverse events
Selection of a 50 mg/kg dose in rats was equivalent to the 6mg/kg or about 400 mg once daily in humans. A human dose of 250 mg twice a day, which was well-tolerated in the Phase 1 study, provides ANG-3070 exposures well above those seen as necessary for activity in animal models. Finally, the multi-colored bar on the right side of the graph shows the no adverse event level in non-human primates was not seen until about 250 mg/kg, or an equivalent human dose of about 5,600 mg once daily. Taken together, these exposure data demonstrate a large margin between doses seen as active in animal studies and much higher dose levels required to show toxicity in animal models.
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Based upon the Phase 1 study data, in December 2021 we enrolled the first patient in JUNIPER, a randomized, multi-center, double-blind, and placebo-controlled globalrecommended Phase 2 dose finding studyof 10.0mg Amph-CpG-7909
84% of patients generated mKRAS-specific T cell responses with a 58x average fold-change compared to baseline
59% of patient responses included both CD4 and CD8 T cells
84% of patients had a decline in PPKD patients focused on FSGStheir tumor biomarker from baseline
100% of the above median T cell group achieved tumor biomarker responses to ELI-002; in the below median group 67% (8/12) responded to ELI-002
At a median follow up of 8.5 months, the median RFS was not reached for above median T cell responders compared to 4.01 months among below median T cell responders (HR 0.14, 95% CI 0.03-0.63, P=0.0167)
86% Reduction in Risk of Progression or Death in the above median T cell responders to ELI-002
Median overall survival was not reached for either group
Median relapse free survival of 16.3 months for 25 patient cohort
With the return of contract manufacturing capacity in 2022 and IgAN. The study planresulting availability of the 7-peptide version of ELI-002, that covers seven of the most common KRAS mutations thereby increasing the eligible patient population for ELI-002 and potentially reducing the chance of tumor bypass resistance mechanisms, we do not intend further studies of the 2-peptide version of ELI-002.
AMPLIFY-7P Phase 1/2 clinical trial (NCT05726864)
This trial is to enroll appropriately 100assess the safety and efficacy of the 7-peptide version of ELI-002 as adjuvant monotherapy treatment in patients at a 1:1:1:1 ratio to ANG-3070, 200 mg QD (once daily), 400 mg QD, 300 mg BID (twice daily), or placebo (QD or BID) administered dailywith solid tumors carrying mutated KRAS. In April 2023, we initiated dosing of the Phase 1A portion of the trial enrolling 14 patients through October 2023 who will be evaluated for 12 weeks. The primary endpoint issafety and efficacy of two ELI-002 AMP-peptide total dose levels (1.4mg and 4.9mg) in combination with the percentage change in urinary protein/creatinine ratio (UPCR) at week 12.10.0mg Phase 2 dose of Amph-CpG-7909. In September 2023 the Independent Data Monitoring Committee (“IDMC”) reviewed the available Phase
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Key1A data and determined enrollment criteria for the Phase 2 portion of the study include:could be opened. Preliminary results from the Phase 1A trial are expected in the second quarter of 2024.
DiagnosisIn January 2024, we announced the first patient had been dosed in the randomized Phase 2 trial of IgAN or primary FSGS confirmed by past renal biopsy or genetic forms of FSGS onELI-002 7P as an adjuvant monotherapy treatment for patients with KRAS-mutated PDAC. The Phase 2 trial will assess disease free survival (DFS) in ~90 patients with PDAC who receive ELI-002 7P (10.0 mg AMP-CpG and 4.9 mg AMP-peptides 7P) as compared to ~45 patients with PDAC who receive standard of care (SoC) for at least 12 weeks prior to enrollment
eGFR > 40mL/min/1.73m2, urinary protein > 1g/day, stable blood pressure, SoC background therapy of ACEi or ARB(observation) with up to 20 patients with and eGFR > 30 but < 40mL/min/1.73m2
Any other RAAS/SGLT-2/immunomodulatory medications must be stable for prior 12 weeks.
The goalscrossover of the JUNIPER study are:observation arm permitted at the time of confirmed radiographic relapse via iRECIST. We expect enrollment of the 135 patients to complete by year-end 2024 with interim analysis results in the first quarter of 2025.
ELI-007:Provide enough information of effect of ANG-3070 on proteinuria to determine a regulatory strategy in PPKD patients AMP Immunotherapy for mutant BRAF-driven Cancers
DetermineELI-007 is a multivalent lymph node–targeted AMP peptide vaccine developed to target 95% of the proper doseBRAF gene mutations found in solid tumors. The BRAF gene is part of an intracellular signaling pathway that drives cell growth and division. BRAF mutations can lead to uncontrolled cell growth and are present in multiple types of cancer, including 40% in melanoma, 9% in CRC, and 2% in lung cancer. High levels of BRAF protein expression in these tumors suggest susceptibility to T cells targeting the mutated protein. We received funding for subsequent studiesthe initial development of ELI-007 through two grants from the Gastro-Intestinal (“GI”) Research Foundation.
Discover whetherAt the proper dose may be differentNovember 2023 Society for IgAN patients than FSGS patients
Gather additional safety, tolerability, biomarker, and PK/PDImmunotherapy of Cancer annual meeting, we presented preclinical data on ANG-3070
demonstrating ELI-007 can generate robust mutant BRAF-specific polyfunctional T cell responses in a murine model. We are also planningcurrently evaluating opportunities to advance ELI-007 through partnerships, collaborations or additional grants.
ELI-008: AMP Immunotherapy for mutant TP53-expressing Cancers
ELI-008 is a Phase 1B study in patients with IPF,multivalent lymph node–targeted AMP peptide vaccine developed to begin in 2022. The preliminary plantarget p53 hotspot mutations. p53 is a tumor-suppressing protein that controls DNA replication processes where mutated p53 protein contributes to enroll IPF patients who are either treatment naïve or have been proven intolerant of approved therapiesuncontrolled cell growth and tumor progression. We designed ELI-008 to evaluate the pharmacokinetics and safety and tolerability of ANG-3070. Subsequently, we are planning a Phase 2 study where the primary endpoint is likely to be pulmonary function tests at 6-12 months and we expect this trial to also compare multiple doses of ANG-3070 against placebo.
In addition to the Phase 1 data in healthy volunteers, the clinical plans for ANG-3070 in kidney and pulmonary fibrosis are supported by a broad program of preclinical animal studies. ANG-3070 has demonstrated activity in preclinical models across renal and pulmonary fibrosis.

ANG-3777
ANG-3777 was designed to be a first-in-class hepatocyte growth factor (HGF) mimetic. We engineered ANG-3777 to mimic the biological activity of HGF in activating critical pathways in the body’s natural organ repair process following an acute organ injury. In 2021, we reported the results of three clinical trials of ANG-3777. Nonetarget ~30% of the trials were positive on their primary endpoints, but we believe ANG-3777 demonstrated biologic activityp53 hotspot mutations found in solid tumor cancers including melanoma, CRC, and NSCLC. We received funding for the Phase 3 trialinitial development of kidney transplant patients with delayed graft function (DGF) and in the Phase 2 trial in patients at risk for acute kidney injury associated with cardiac surgery involving cardiopulmonary bypass (CSA-AKI).
We continue to work with our license partner Vifor Pharma on the process of closing out our analyses of dataELI-008 through two grants from the 2021 clinical trial readouts.GI Research Foundation.
At the November 2023 Society for Immunotherapy of Cancer annual meeting, we presented preclinical data demonstrating ELI-008 can generate robust mutant p53-specific polyfunctional T cell responses in a murine model. We do not intendare currently evaluating opportunities to continue the clinical development plan for ANG-3777 set forth in the Vifor License, which had included a Phase 3 study in CSA-AKI and a Phase 4 confirmatory study in DGF, given these clinical results. There are no funds budgeted foradvance ELI-008 through partnerships, collaborations or additional clinical trials for ANG-3777.grants.

AMP Platform Potential Beyond Cancer Vaccines
Our Preclinical Pipeline
We plan to select clinical lead candidatesAMP platform has broad potential applications for onethe treatment or moreprevention of these preclinical programs and begin IND-enabling studies by the end of 2022.

ROCK2 Program for Fibrotic and Other Diseases
Our ROCK2 program includes a number of highly selective, oral, small molecule inhibitors of ROCK2 developed internally as a potential treatment for fibroticcancer, infectious diseases and other diseases. Rho-associated coiled-coil forming protein kinase (ROCK) signal transduction pathways are implicatedThese other applications include immune cell therapy AMP-lifiers for CAR T cell therapeutics and TCR T cell therapeutics. We have also completed preclinical proof-of-concept assessments related to the intranasal and subcutaneous use of the AMP platform to prevent infectious diseases, including COVID-19. We intend to advance additional applications of the AMP platform via out-licensing, co-development, or other partnership arrangements.
TCR T Cell Therapy Preclinical Data
In January 2024, data from preclinical studies was published in Cancer Immunology Research demonstrating our AMP immunotherapy in combination with TCR-T cell therapy led to complete eradication and durable responses against established murine solid tumors refractory to TCR-T cell monotherapy. Our AMP immunotherapy led to enhanced lymph node delivery and correlated with pro-inflammatory lymph node transcriptional reprogramming and increased antigen-presenting cell maturation, resulting in TCR-T cell expansion and functional enhancement. Addition of AMP immunotherapy enhanced the infiltration and function of TCR-T cells in the developmenttumor microenvironment and led to antigen spreading against diverse tumor targets. We are currently evaluating opportunities to advance our AMP immunotherapy application to TCR-T cell therapy through partnerships or collaborations.
Licensing, Collaboration and Partnership Agreements
MIT License Agreement
On January 27, 2016, we entered into an Exclusive Patent License Agreement with Massachusetts Institute of fibrosis. Inhibition of the ROCK isoforms ROCK1 and ROCK2 has shown promise in treating fibrosis in animal models. However, use of a non-isoform-specific ROCK inhibitor (i.e.Technology (“MIT”), dually inhibits ROCK1 and ROCK2)which has been associatedamended from time to time (the “MIT License Agreement”). Pursuant to the MIT License Agreement, we were granted an exclusive, worldwide license, with inducing hypotension. Recent scientific workthe right to sublicense, to certain patents and patent applications owned by MIT related to the AMP technology for the diagnosis, treatment or prevention of diseases. The licensed patent claims cover vaccine products in development by us for our current lead programs in tumor indications where mutant KRAS, rearranged Anaplastic lymphoma kinase (“ALK”), or certain other proteins are a driver of disease, as well as programs using specific genetic or pharmacological inhibition of ROCK2 indicates ROCK2 inhibition alone can resultCpG as an adjuvant for immune activation in anti-fibrotic activity without causing hypotension. These findings informed our strategy to develop ROCK2-specific inhibitors as a potential treatment for fibrosis.
Multiple dual ROCK1/2 inhibitors have received regulatory approval, including ripasudil (Glanatec®), which is approved in Japan for treating glaucomaconjunction with an immunostimulatory agent. The MIT License Agreement established annual license payment obligations and ocular hypertension, fasudil (ErilTM), which is approved in Japan and
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Chinaintellectual property cost reimbursement obligations for treating cerebral vasospasmwhich we are responsible, specific product categories (including immunotherapeutic products and adjuvant products) for which we are required to invest specified minimum amounts of research funding and the timing of such investment, specified development and commercialization milestone obligations, and payments due with respect to the achievement of these milestones.
On October 21, 2016, the MIT License Agreement was amended to update language around patent rights and MIT procedures. On February 22, 2018, the MIT License Agreement was amended to extend certain milestone dates. On each of January 31, 2019, June 23, 2020 and January 7, 2021, the MIT License Agreement was amended to add certain patent applications owned by MIT and include an additional fee, updates to patent application fees and to annual license maintenance fees. The amendments on June 23, 2020 and January 7, 2021 also adjusted milestone dates and diligence requirements under the MIT License Agreement.
Under the terms of the MIT License Agreement, we are obligated to use commercially reasonable diligent efforts to develop and commercialize licensed products, and to use such efforts to accomplish specified development and commercial launch objectives in hemorrhagic stroke,accordance with a specified timeline as well as to expend specified resources in the development and netarsudil (Rhopressa®),commercialization of immunotherapeutic products and adjuvant products. We are obligated to pay an annual license maintenance fee, which can be credited against royalties paid to MIT during the same calendar year. We are also obligated to make milestone payments upon the occurrence of specific development and commercialization achievements on a product-by-product basis during the term of the MIT License Agreement, including those relating to the making of certain regulatory filings, the initiation of certain clinical trials and the achievement of certain sales thresholds. The achievement of each milestone triggers the payment of a set dollar amount to MIT by us. These milestone payments could, in the aggregate, reach a maximum of $27.5 million. We are obligated to make royalty payments based on net sales by it and its sublicensees equal to (i) a fractional to low single digit percentage of net sales of products that would infringe the MIT patent rights and (ii) a fractional percentage of net sales of products that could not have been identified, selected, or determined to have biological activity but for the use or modification of products that would infringe the MIT patent rights. These royalty rates are subject to an upward adjustment if we or a sublicensee commence an action against MIT to declare or render invalid or unenforceable any of the licensed patent rights; and the amount of royalties payable to MIT are subject to a downward adjustment if we are required to secure certain patent licenses from third parties to avoid infringement by the practice of the licensed patent rights. These royalties are payable (1) until the expiration of the last to expire of the MIT patent rights with respect to products that would infringe the MIT patent rights and (2) for 12 years following the first commercial sale of products that could not have been identified, selected, or determined to have biological activity but for the use or modification of products that would infringe the MIT patent rights.
We are also obligated to pay a percentage of any revenue that it or its sublicensees earn from the provision of services using licensed products or that utilizes a process that would infringe the MIT patent rights. We are also obligated to pay a percentage of any payments it receives from its sublicenses, with certain exceptions. We are also required to share a portion of any funds it or a sublicensee receives in respect of the sale of a regulatory voucher that is approvedgranted by any regulatory authority based upon the regulatory approval of a product subject to the MIT License Agreement for the treatment of a neglected disease. MIT controls the prosecution and maintenance of the licensed patent rights, and we are required to pay all costs and fees associated with patent prosecution and maintenance of the licensed patents. Patent protection for the MIT licensed patents is being sought in the United States for the treatment of glaucoma. and elsewhere, including Australia, Canada, Europe, Hong Kong and Japan.
The ROCK2-selective inhibitor belumosudil has been approved by the FDA for the treatment of chronic graft-versus-host disease.
Elevated expression of ROCK2 has been implicated in a number of chronic fibrotic conditions and other diseases. ROCK2 is significantly upregulated in fibrotic kidneys in both pediatric and adult patients, with ROCK2 levels positively correlated with the severityterm of the fibrosis. StudyMIT License Agreement will continue in effect until the expiration or abandonment of ROCK2 inhibition inall issued patents and filed patent applications within the unilateral ureteral obstruction (UUO) modellicensed patent rights, unless earlier terminated. MIT may terminate the MIT License Agreement upon our uncured material breach of renal fibrosis showed ROCK2 inhibition alleviates renal fibrosis. Furthermore, inthe MIT License Agreement or upon the occurrence of certain events, including if we or a mouse modelsublicensee commence an action against MIT to declare or render invalid or unenforceable any of IPF, researchers found mice with either ROCK1the licensed patent rights, or ROCK2 genetically deleted were protected from bleomycin-induced IPF, indicating specifically targeting either ROCK isoform would be an effective therapeutic strategy against IPF. ROCK2 expression in vitro has also been associated with co-expressionupon specified insolvency or bankruptcy events concerning us. We may terminate the MIT License Agreement without cause upon six months advance written notice to MIT and upon payment of fibrotic liver markers. Elevated ROCK2 levels are seen in cardiac hypertrophy, cardiac fibrosis and diastolic dysfunction. ROCK2 has also been shown to play a role in neurodegenerative disordersall amounts due MIT through the date such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease. As a result, we believe a potent ROCK2 inhibitor should prevent disease progression in chronic fibrotic diseases and potentially be useful in a variety of other cardiac and neurodegenerative disorders.
Dual ROCK1/2 inhibitors can have problematic side effects including hypotension and increased vascular permeability. In an in vitro analysis measuring binding affinity for ROCK2 and ROCK1, our ROCK2 selective inhibitors show much stronger binding affinity for ROCK2 versus ROCK1. We believe high selectivity for ROCK2 could provide enhanced tolerability, potentially supporting long-term systemic use.termination takes effect.

CYP11B2 (Aldosterone Synthase) Inhibitor Program
Aldosterone is a hormone produced in the adrenal glands which helps control the body's blood pressure by causing the kidneys to retain salt and excrete potassium, thereby increasing water retention, blood volume and blood pressure. CYP11B2 is a member of the broad cytochrome P450 family and is responsible for the biosynthesis of aldosterone. There are a number of diseases associated with dysregulated aldosterone, including primary hyperaldosteronism (Conn's Syndrome), refractory hypertension, congestive heart failure and kidney fibrosis. As a result, we believe inhibition of CYP11B2 could potentially be used in aldosterone-related diseases.
The renin-angiotensin-aldosterone system (RAAS) is responsible for producing aldosterone to maintain blood pressure. Two major approaches to modulating the RAAS pathway are angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs). There are eighteen FDA-approved ACE inhibitors/ARBs, and while these drugs are generally quite effective in controlling hypertension, aldosterone breakthrough or escape happens in approximately 10% to 50% of patients depending on the duration of therapy studied and the definition of 'breakthrough'. Aldosterone excess is estimated to be the primary cause in approximately 20% of patients with resistant hypertension, or nearly 2 million patients in the United States alone.
Two hormonal mineralocorticoid receptor antagonists (MRAs), spironolactone and eplerenone, plus a non-steroidal MRA (finerenone), are also involved in blocking the effects of aldosterone. MRAs act by binding to the mineralocorticoid receptor to prevent aldosterone from having its biologic effect on blood pressure and renal excretion and absorption of salt and potassium. However, approved MRAs have the downside of increasing circulating levels of aldosterone, leading to increased activity of aldosterone through its non-MR mechanisms. Aldosterone acts on the vascular system by inducing oxidative stress, inflammation, fibrosis and endothelial dysfunction through both MR-dependent and MR-independent pathways. As such, increased levels of aldosterone have direct deleterious effects on the progression of congestive heart failure and renal fibrosis.
We have created a selection of molecules with high specificity to CYP11B2 relative to CYP11B1 and continue work towards selecting a clinical lead for the program.
Manufacturing
We rely upon third-party contract manufacturing organizations to manufacture and supply product candidates for our clinical trials, and we will rely on such manufacturers to meet commercial demand. We expect this strategy will enable us to maintain a more efficient infrastructure, avoiding dependence on our own manufacturing facility and equipment, while simultaneously enabling us to focus our expertise on the clinical development and future commercialization of our products. Currently, we rely on and have agreements with a single third-party contract manufacturer to supply the drug substance for ANG-3070 and with a single third-party contract manufacturer to
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manufacture all clinical trial supplies of ANG-3070. We currently have sufficient inventory of ANG 3070 to meet all requirements for our planned clinical trials. We expect to qualify additional suppliers for ANG 3070 drug substance and ANG 3070 clinical trials supplies to support future clinical trials, and we expect to enter into commercial supply agreements with such manufacturers prior to any potential approval of ANG 3070. ANG-3070 drug substance is manufactured via conventional organic synthetic procedures, starting from raw materials and reagents commercially available in large quantities. ANG-3070 drug product is manufactured via conventional pharmaceutical processing procedures, employing commercially available excipients and packaging materials. The procedure and equipment employed for manufacture and analysis are consistent with standard organic synthesis or pharmaceutical production, and are transferable to a range of manufacturing facilities, if needed.
We are in discussions with third party manufacturers to identify additional suppliers to produce our other product candidates.
Competition
The biotechnology and pharmaceutical industries are characterized by intense competition and rapid innovation. Although we believe our product candidates offer innovative therapeutic approaches and may provide significant advantages relative to current therapies in the treatment of acute organ damage and our other therapeutic areas, our competitors may be able to develop other compounds, drugs, or therapies capable of achieving similar or better results. Our potential competitors include major multinational pharmaceutical companies, established biotechnology companies, specialty pharmaceutical companies and universities and other research institutions. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies. We believe the key competitive factors affecting the development and commercial success of our product candidates will be whether or not such product candidates are deemed to be safe and effective by relevant regulatory authorities, as well as their tolerability profile, reliability, convenience of dosing, price, and reimbursement.
With respect to ANG-3070, clinical programs potentially competitive in PPKDs generally focus on immune system modification, repurposed or novel hemodynamic (blood pressure) modifiers, and other approaches. In contrast, we believe ANG-3070 is the only clinical-stage anti-fibrotic in development for PPKDs. Given the disease progression path for PPKDs, programs not specifically addressing renal fibrosis have the potential to be more complimentary than competitive. In 2021, Tarpeyo® (budesonide) from Calliditas was granted accelerated approved by the FDA for IgAN, one form of PPKD. Phase 3 programs in PPKD include:
Atrasentan from Chinook Pharmaceuticals (IgAN, FSGS, Alport)
Bardoxolone methyl from Reata Pharmaceuticals (Alport)
Iptacopan from Novartis (IgAN)
Narsoplimab form Omeros (IgAN)
Sibeprenlimab from Visterra/Otsuka Pharmaceuticals (IgAN)
Sparsenten from Travere Therapeutics (IgAN, FSGS)
DMX-200 from Dimerix (FSGS)
Phase 3 clinical programs potentially competitive with ANG-3070 in pulmonary fibrosis (IPF and SSc-ILD) include:
There are two approved therapies, pirfenidone (Esbriet®, sold by Roche/Genentech) for IPF and nintedanib (OFEV®, sold by Boehringer-Ingleheim) for IPF and SSc-ILD.
ORG-447 from Agomab Therapeutics for IPF
PLN-74809 from Pliant Therapeutics for IPF
PRM-151 from Roche/Genentech for IPF
Taladegib from Endeavor Biosciences for IPF
With respect to competition for our ROCK2 inhibitor program:
Netarsudil ophthalmic solution from Aerie Pharmaceuticals, Inc. was first approved by the FDA in 2017 as a topical agent for reducing intraocular pressure in patients with open-angle glaucoma and ocular hypertension
Kadmon Holdings, Inc.'s belumosudil (KD025), a ROCK2 inhibitor with reduced selectivity against ROCK1, in the clinic for several indications, and approved for chronic graft versus host disease
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Fasudil developed by Asahi Kasei approved in Asia is being investigated by Woolsey Pharmaceuticals in ALS, retinopathy of prematurity, and dementia
CXC007 from Redx Pharma Plc
Other ROCK2 inhibitors in preclinical development.
Regarding competition for our CYP11B2 inhibitor program:
CIN-107 from CinCor Pharma is a CYP11B2 inhibitor in multiple Phase 2 trials for resistant hypertension, uncontrolled hypertension, and primary aldosteronism.
PB6440 from PhaseBio is a CYP11B2 inhibitor preparing for Phase 1 trials in 2022 in treatment resistant hypertension
Across each of our development areas, other, potentially competitive, clinical-stage technologies are being developed. Also, companies developing preclinical molecules could decide to pursue development in our chosen indications and potentially compete with us. This could lead to commercial challenges as well as difficulties enrolling clinical trials if they were to target the same indications we are pursuing.
Intellectual Property
TheIntellectual property is of vital importance in our field and in biotechnology generally. We seek to protect and enhance proprietary nature of,technology, inventions, and protection for, our product candidates, processes and know-howimprovements that are commercially important to the development of our business.business by seeking, maintaining, and defending patent rights, whether developed internally or licensed from third parties. We pursue various avenues of intellectual propertywill also seek to rely on regulatory protection including consideration ofafforded through inclusion in expedited development and review, data exclusivity, market exclusivity and patent trademark, and trade secret strategies. term extensions where available.

We have sought patent protection in the United States and internationally related to the AMP platform technology as well as the mKRAS and universal adjuvant programs. We have issued patents in Japan, Nigeria, Russia, and Singapore covering clinical product candidates but the patent portfolio owned by us currently largely
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comprises pending applications. Such applications may not result in issued patents and, even if patents do issue, such patents may not be in a form or scope that will provide us with meaningful protection for our programs relating to small molecule compounds with our tyrosine kinase inhibitors (including ANG-3070), HGF-like activity (including ANG-3777), our ROCK2 inhibitors and our CYP inhibitors. Our patent strategy seeks to protect our product candidates by filing patent applications, in the United States and in relevant foreign jurisdictions, and we pursue multi-faceted protection, as available, for example to relevant small molecule compounds and analogs, pharmaceutical compositions and related methods of manufacture and use. Our policy is to pursue, maintain and defend patent rights in order to protect the technology, inventions and improvements that are commercially important to our business.candidates. We also rely on trade secret protection for certain intellectual propertysecrets that may be important to the development of our businessbusiness. Trade secrets are difficult to protect and provide us with only limited protection, as trade secrets do not protect against independent development of a technology by third parties.
We expect to pursue trademark registrations for brand names or other text or images that may provide commercial value.
In the United Statesfile additional patent applications in support of current and worldwide, issued patents have a presumptive term, assuming all maintenance fees are paid, of twenty years from their earliest non-provisional filing date. Certain jurisdictions offer opportunities to extend this term. For example, the U.S. Patentnew clinical candidates as well as new platform and Trademark Office (USPTO) may add term to a patent (referred to as Patent Term Adjustment) if delays by the USPTO of certain activities exceed prespecified durations, from which delays by the Applicant are subtracted. Additionally, many jurisdictions, including the United States and Europe, provide opportunities for extending the term of patents relating to approved pharmaceutical products or their approved uses. In the United States, a single patent can be extended per approved product, for a period (referred to as Patent Term Extension) of up to five years, depending on the dates of patent issuance relative to submission of an application for premarketing approval (i.e., of a New Drug Application or a Biologics License Application) under provisions of the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Act. Similar restoration of term is available in Europe under so-called Supplementary Protection Certificate rights, and extensions under similar policies may be available in other countries.
Depending upon the timing, duration and specifics of FDA marketing approval of our product candidates, if any, one or more of our patents may be eligible for limited Patent Term Extension under the Hatch-Waxman Act in the United States, Supplementary Protection Certificate in Europe.
core technologies. Our commercial success will depend in part on obtaining and maintaining patent protection and/or other intellectual propertyand trade secret protection for ourof current and future product candidates including for their use, production, formulation, etc., with commercially relevant terms; our commercial success may also depend in part on our abilityand the methods used to develop and manufacture them, as well as successfully defend our patent and/or other intellectual property rightsdefending any such patents against third-party challenges.challenges and operating without infringing on the proprietary rights of others. Our ability to stop third parties from making, using, selling, offering to sell and/or importing our products mayproduct candidates will depend on the extent to which we have rights under valid and enforceable intellectual property rightspatents or trade secrets that cover these activities. We cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future, nor can we be sure that any of our existing patents or any patents that may be granted to us in the future will be commercially useful in protecting our product candidates, discovery programs and processes. Additionally,
The terms of individual patents depend upon the legal term of the patents in the countries in which they are obtained. In most countries in which we file, including the United States, the patent term is 20 years from the earliest date of filing a non-provisional patent application. In the United States, a patent term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the U.S. Patent and Trademark Office (“USPTO”) in examining and granting a patent or may be shortened if a patent is terminally disclaimed over an earlier filed patent. In the United States, the term of a patent that covers an FDA-approved drug may also be eligible for extension, which permits patent term restoration to account for the patent term lost during the FDA regulatory review process. The Hatch-Waxman Act permits a patent term extension of up to five years beyond the expiration of the patent. The length of the patent term extension is related to the length of time the subject drug candidate is under regulatory review. Patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent applicable to an approved drug may be extended and only those claims covering the approved drug, a method for using it, or a method for manufacturing it may be extended. Similar provisions to extend the term of a patent that covers an approved drug are available in Europe and other foreign jurisdictions. In the future, if and when our products receive FDA approval, we expect to apply for patent term extensions on patents covering those products. We plan to seek patent term extensions to any issued patents we may obtain in any jurisdiction where such patent term extensions are available, however there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment that such extensions should be granted, and if granted, the length of such extensions.

In some instances, we have submitted and expect to submit patent applications directly to the USPTO as provisional patent applications. Corresponding non-provisional patent applications must be filed not later than 12 months after the provisional application filing date. While we intend to timely file non-provisional patent applications relating to our provisional patent applications, we cannot predict whether any such patent applications will result in the issuance of patents that provide us with any competitive advantage.
We file U.S. non-provisional applications and Patent Cooperation Treaty (“PCT”) applications that claim the benefit of the priority date of earlier filed provisional applications, when applicable. The PCT system allows a single application to be certainfiled within 12 months of the original priority date of the patent application, and to designate all of the PCT member states in which national patent applications can later be pursued based on the international patent application filed under the PCT. The PCT searching authority performs a patentability search and issues a non-binding patentability opinion which can be used to evaluate the chances of success for the national applications in foreign countries prior to having to incur the filing fees. Although a PCT application does not issue as a patent, it allows the applicant to seek protection in any of the member states through national-phase applications. At the end of the period of two and a half years from the first priority date of the patent application, separate patent applications can be pursued in any of the PCT member states either by direct national filing or, in some cases by filing through a regional patent organization, such as the European Patent Office. The PCT system delays expenses, allows a limited evaluation of the chances of success for national/regional patent applications and enables substantial savings where applications are abandoned within the first two and a half years of filing.
For all patent applications, we determine claiming strategy on a case-by-case basis. Advice of counsel and our business model and needs are always considered. We seek to file patents containing claims for protection of all useful applications of our proprietary technologies and any products, as well as all new applications and/or uses that we will always be ablediscover for existing technologies and products, assuming these are strategically valuable. We continuously reassess the number and type of patent applications, as well as the pending and issued patent claims to establish sufficientpursue maximum coverage and value for our processes, and compositions, given existing patent office rules and
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ownership rightsregulations. Further, claims may be modified during patent prosecution to ensure complete or necessary control overmeet our intellectual property rights as required in orderand business needs.
We recognize that the ability to obtain patent protection and the degree of such protection depends on a number of factors, including the extent of the prior art, the novelty and non-obviousness of the invention, and the ability to satisfy the enablement requirement of the patent laws. In addition, the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can be reinterpreted or further altered even after patent issuance. Consequently, we may not obtain or maintain adequate patent protection for any of our future product candidates or for our technology platform. We cannot predict whether the patent applications we are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient proprietary protection from competitors. Any patents that we hold may be challenged, circumvented or invalidated by third parties.
In addition to patent protection, we also rely on trade secrets, know how, other proprietary information and continuing technological innovation to develop and maintain our competitive position. We seek to protect and maintain the confidentiality of proprietary information to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection. Although we take steps to protect our proprietary information and trade secrets, including through contractual means with our employees and consultants, third parties may independently develop substantially equivalent proprietary information and techniques or otherwise gain access to our trade secrets or disclose our technology. Thus, we may not be able to meaningfully protect our trade secrets. It is our policy to require our employees, consultants, outside scientific collaborators, sponsored researchers and other advisors to execute confidentiality agreements upon the commencement of employment or consulting relationships with us. These agreements provide that all confidential information concerning our business or financial affairs developed or made known to the individual during the course of the individual’s relationship with us is to be kept confidential and not disclosed to third parties except in specific circumstances. Our agreements with employees also provide that all inventions conceived by the employee in the course of employment with us or from the employee’s use of our confidential information are our exclusive property. However, such confidentiality agreements and invention assignment agreements can be breached and we may not have adequate remedies for any such breach. In addition, our trade secrets may otherwise become known or be independently discovered by competitors. To the extent that our consultants, contractors or collaborators use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting trade secrets, know-how and inventions.
The patent positions of biotechnology companies are generally uncertain and involve complex legal, scientific and factual questions. Our commercial success will also depend in part on not infringing upon the proprietary rights of third parties. Third-party patents could require us to alter our development or commercial strategies, or our products or processes, obtain licenses or cease certain activities. Our breach of any license agreements or our failure to obtain a license to proprietary rights required to develop or commercialize our future products may have a material adverse impact on us. If third parties prepare and file patent applications in the United States that also claim technology to which we have rights, we may have to participate in interference or derivation proceedings in the USPTO to determine priority of invention. For more information, see “Risk Factors—Risks Related to Intellectual Property.”
When available to expand market exclusivity, our strategy is to obtain, or license additional intellectual property related to current or contemplated development platforms, core elements of technology and/or enforce them. For theseproduct candidates.
Company-owned Intellectual Property
We own the following patent families and more comprehensive risks related to our intellectual property, please see "Risk Factors—Risks Relating to Our Intellectual Property." The expiration dates of the patents discussed below assume in all cases that the appropriate maintenance, renewal, annuity, or other governmental fees are paid to maintain the patent(s) in force for the full extent of their termapplications:
We have an issued U.S. patent and any extension(s) thereof.

ANG-3070 Tyrosine Kinase Inhibitor Program
As of January 1, 2022, compound, pharmaceutical compositionpending U.S. and Canadian patent applications titled “ALK polypeptides and methods of use claimsthereof”, which are related to our kinase inhibitors are coveredproducts in development for tumor indications where rearranged ALK is a driver of disease.
We also have a patent family titled “Compounds including a mutant KRAS sequence and a lipid and uses thereof” with granted patents issuedin Japan, Russia and Singapore and pending applications in the United States. We also owned issued patents inStates, the United Arab Emirates, Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, India, Japan;Japan, South Korea, Mexico, Malaysia, Nigeria, New Zealand, Saudi Arabia, Thailand, Ukraine, and South Africa. This patent family relates to our products in development for tumor indications where mutant KRAS is a driver of disease.
We also have a patent family titled “CpG amphiphiles and uses thereof” with granted patents in Nigeria and Singapore and pending applications in the United States, the United Arab Emirates, Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, Russia, Saudi Arabia, Thailand, Ukraine, and South Africa. This patent family relates to our products in development for tumor indications where expression of human papillomavirus protein(s) is a driver of disease.
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We also have a patent family titled “Compositions and methods for inducing an immune response against coronavirus” with pending applications in the United States, Australia, Brazil, Canada, China, Europe, Hong Kong, India, Japan, South Korea, and Mexico. This patent family relates to the use of our AMP technology, including products in development, in methods of inducing an immune response against coronavirus.
We also have a patent family titled “Uses of amphiphiles in immune cell therapy and compositions therefor” with pending applications in the United States, Australia, Canada, Europe, Japan, and New Zealand. This application relates to the use of our AMP technology, including products in development, in immune cell therapy.

We also have a patent family titled “Compositions containing polynucleotide amphiphiles and methods of use thereof”with pending applications in the United States, Australia, Canada, Europe, Japan, and New Zealand. This application relates to aspects of our AMP technology platform.
We also have a pending U.S. provisional application titled “Compositions containing polynucleotide and polypeptide amphiphiles and methods of use thereof.” This application relates to aspects of our AMP technology platform.
We also have two pending U.S. provisional applications titled “Compositions containing mutant p53 peptide amphiphiles and methods of use thereof.” These applications relate to aspects of our AMP technology platform.
We have sole ownership of the above patents and patent applications. For these patents and for any patents granted on the pending applications, we anticipate that patent expiration would occur between 2037 and 2044 without taking into consideration patent term adjustments or extensions.
We also have a pending PCT international application titled “Uses of amphiphiles in immune cell therapy and compositions therefor.” This application relates to aspects of our AMP technology platform in connection with immune cell therapy.This application is co-owned with the University of Pennsylvania. If we are granted patents on this pending application, it is anticipated that patent expiration would occur in 2043 without taking into consideration patent term adjustments or extensions.
We also have two pending U.S. provisional applications titled “Compositions containing BRAF peptide amphiphiles and methods of use thereof.” These applications relate to aspects of our AMP technology platform. These applications are co-owned with Cornell University. If we are granted patents on non-provisional applications based on these pending applications, it is anticipated that patent expiration would occur in 2044 without taking into consideration patent term adjustments or extensions.
Licensed Intellectual Property
We have an exclusive license from MIT for six patent families related to aspects of our AMP technology platform:
“Immunostimulatory compositions and methods of use thereof”, which contains three patents granted in the United States, patents granted in Europe, Hong Kong, and Japan, as well as pending applications in the United States, Europe, Hong Kong, and Japan, which relates to aspects of our AMP platform technology;
“Albumin binding peptide conjugates and methods thereof,” which contains two patents granted in the United States, as well as pending applications in the United States, China, Hong Kong, Japan, and Europe, which relates to certain additional aspects of our AMP platform technology;
“Chimeric antigen receptor-targeting ligands and uses thereof” with a pending application in Canada. The European patent was validated in Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Luxembourg, Monaco, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland/Liechtenstein, Turkey, and the United Kingdom. A continuation application is pending in the United States. These patents, and patents that may issue from the pending applications, provide patent protection until 2033, assuming payment of all appropriate annuities and/or maintenance fees.
We have filed a PCT application directed to the use of ANG-3070 in the treatment of irritable bowel syndrome (IBS). Patents issuing from corresponding national applications will expire in 2040.
As of January 1, 2022, we had filed three PCT applications relating to solid forms of ANG-3070, methods of treating fibrotic diseases, and biomarkers relating to ANG-3070, whose twenty-year presumed terms expire in 2041.
As of January 1, 2022, we had filed a provisional patent application relating to gene expression levels associated with treatment comprising ANG-3070.
Under the Hatch-Waxman Act, a single patent term restoration of up to five years in the United States, may be available. We also may be eligiblewhich relates to further aspects of our AMP platform technology;
“Compositions for similar restoration of term in Europe under supplementary protection certificate rights,chimeric antigen receptor T cell therapy and similar extensions in certain other countries.
ROCK2 Inhibitor Program
The patent portfolio for the ROCK2 inhibitor program includesuses thereof” with pending applications in the United States, Australia, Canada, China, Europe, Israel, India,Hong Kong, Japan, South Korea, Mexico, New Zealand, and Japan, eachRussia, which relates to the use of which would have presumed twenty-year terms expiringour AMP platform technology in 2038. We have also filed a Patent Cooperation Treaty (PCT)connection with CAR T therapy;
“Uses of amphiphiles in immune cell therapy and compositions therefor” with pending application and a provisional application, each of which recite claims to compounds, pharmaceutical compositions, and methods of use thereof. Any patents that may issue from national applications of the PCT application or the provisional application would have twenty-year presumed terms expiring between 2040 and 2041.
CYP11B2 Inhibitor Program
The patent portfolio for the CYP11B2 inhibitor program includes pending applications in the United States, Australia, Canada, Europe, Israel,Hong Kong, and Japan, eachwhich relates to use of which would have presumed twenty-year terms expiringour AMP platform technology in 2038. As of January 1, 2022, we owned issued patentsconnection with immune cell therapy; and
“Methods for identifying chimeric antigen receptor-targeting ligands and uses thereof” with a pending application in the United States, that claim, among other things, ANG-3598 composition of matter, pharmaceutical compositions comprising ANG-3598, andwhich relates to methods of treating renal fibrosis. We also owned issued patentsidentifying further ligands for use in Australia, China, Israel, and India. Each of the patents expire in 2035 and any patents that may issue from the pending applications have twenty-year presumed terms expiring in 2035.
ANG-3777
The patent portfolio for ANG-3777 includes patents and patent applications that describe and/or specifically claim pharmaceutical compositions whose active agent is ANG-3777 and uses thereof, as well as compounds structurally related to ANG-3777, pharmaceutical compositions and uses thereof. As of January 1, 2022, we owned issued patents in the United States that claim, among other things, pharmaceutical compositions comprising ANG-3777. We also owned issued patents in Australia, Canada, China, Europe, Hong Kong, Israel, and Japan. Granted European patents have been validated in the following European countries: Denmark, France, Germany, Hungary, Ireland, Italy, Luxembourg, Monaco, Netherlands, Sweden, Switzerland/Liechtenstein, and the United Kingdom.our AMP platform technology.
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For these patents and for any patents granted on the pending applications, we anticipate patent expiration to occur between 2033 and 2041, without taking into consideration patent term adjustments or extensions.
We also have issued claims to pharmaceutical compositions containing ANG-3777 and methods of use that should remain in force, if the appropriate maintenance, renewal, annuity or other governmental fees are paid, in the United States until 2024, and in other jurisdictions until 2023.
An aqueous formulation of ANG-3777 and analogues of sufficient solubilityan exclusive license from Dr. Roberto Chiarle for intravenous administration is the subject of claims in a patent issuedfamily titled Anaplastic lymphoma kinase (ALK) as oncoantigen for lymphoma vaccination,” which contains two granted U.S. patents. This patent family relates to ALK antigen sequences that may be used in connection with our AMP platform technology. We anticipate patent expiration to occur in 2028 and 2031 without taking into consideration patent term extension.
Manufacturing
We do not own or operate facilities for clinical drug manufacturing, storage, distribution or quality testing. Currently, all of our clinical manufacturing is outsourced to third-party contract manufacturing organizations. We currently obtain our supplies from these manufacturers on a purchase order basis and do not have long-term committed supply arrangements with respect to our product candidates and other materials. Our product candidates are manufactured using reliable and reproducible synthetic processes from readily available starting materials and are based on chemistry that is amenable to scale up. We expect to continue to develop product candidates that can be produced cost effectively at contract manufacturing facilities. See the United Statesrisk factor entitled “We rely on CMOs to manufacture our nonclinical and clinical pharmaceutical supplies and expect to continue to rely on CMOs to produce commercial supplies of any approved product candidate, and our dependence on CMOs could adversely impact its business.”
Competition
The biotechnology and pharmaceutical industries are characterized by rapid evolution of technologies, fierce competition, and strong defense of intellectual property. While we believe our technology, expertise, scientific knowledge, and intellectual property estate provide competitive advantages, we face potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical, biotechnology companies, academic institutions, governmental agencies, and public and private research institutions that conduct research, seek patent protection, and establish collaborative arrangements for research, development, manufacturing, and commercialization. In addition, many small biotechnology companies have formed collaborations with large, established companies to (i) obtain support for their research, development and commercialization of products or (ii) combine several treatment approaches to develop longer lasting or more efficacious treatments that may directly compete with our current or future product candidates. We anticipate that we will expire in 2030 assuming continued paymentcontinue to face increasing competition as new therapies and combinations thereof, technologies, and data emerge within the field of all maintenance fees.
We have issued United States patents on the use of ANG-3777immunotherapy and, related compounds forfurthermore, within the treatment of chronic obstructive pulmonary disease, (COPD),infectious diseases and scleroderma, which expire in 2028cancers.
In addition to the current standard of care treatments for patients, numerous commercial and 2029, respectively.
We have issued claimsacademic preclinical studies and clinical trials are being undertaken by many parties to assess novel technologies and product candidates in the United States to solid formsfield of ANG-3777 which expires in 2040, and pending applications in Australia, Brazil, Canada, China, Eurasia, Europe, Israel, Japan, Korea, Mexico, New Zealand, Singapore, and the United States Patents issuing from these applications will expire in 2040.
We have filed a PCT application directed to the use of ANG-3777 inimmunotherapy. In the treatment of delayed graft function. Patents issuing from corresponding national applications will expiremKRAS associated cancers there are two approved therapies for non-small cell lung cancer (“NSCLC”) Amgen’s LUMAKRAS and Mirati Therapeutics’ KRAZATI. Other companies developing clinical stage personalized cancer vaccine therapies or mKRAS-targeted therapies include BioNTech SE, BridgeBio Pharma Inc., Boehringer Ingelheim, Eli Lilly & Co., Inc., Gritstone bio, Inc., Hookipa Pharma, Roche Holding Ltd./Genentech, Inc., Revolution Medicines, Merck & Co., and Novartis AG.
Many of our competitors, either alone or in 2040.
As of January 1, 2022,combination with their respective strategic partners, have significantly greater financial resources and expertise in research and development, manufacturing, the regulatory approval process, and marketing than we had filed two provisional patent applications relating to ANG-3777 whose twenty-year presumed terms expire in 2041.
Under the Hatch-Waxman Act, a single patent term restoration of up to five yearsdo. Mergers and acquisition activity in the United Statespharmaceutical, biopharmaceutical and biotechnology sector is likely to result in greater resource concentration among a smaller number of our competitors. Smaller or early-stage companies may also prove to be available. Wesignificant competitors, particularly through sizeable collaborative arrangements with established companies. These competitors also compete with us in the recruiting and retaining of qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.
Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, better tolerated, or of greater convenience or economic benefit than any products we may develop. Our competitors also may be eligiblein a position to obtain FDA or other regulatory approval for similar restorationtheir products more rapidly, resulting in a stronger or dominant market position before we are able to enter the market. The key competitive factors affecting the success of term in Europe under supplementary protection, certificate rights, and similar extensions in certain other countries.

Licenses and Collaborations
License Agreement with Vifor Pharma
In November 2020, we granted Vifor Pharma, an exclusive, global (excluding Greater China), royalty-bearing license (the Vifor License), for the commercializationall of ANG-3777 in all Renal Indications, beginning with DGF and CSA-AKI. The Vifor License also grants Vifor Pharma exclusive rights, with a right to sublicense subject to our consent for certain specified conditions, to develop and manufacture ANG-3777 for commercialization in Renal Indications worldwide (excluding Greater China) in cooperation with us or independently. We retain the right to develop and commercialize combination therapy products combining ANG-3777 with our other proprietary molecules, subject to Vifor Pharma's right of first negotiation with respect to global (excluding Greater China) rights to such combination therapy products in the Renal Indications. See Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations. Although the Vifor License includes additional milestone and royalty objectives, we do not expect to receive any clinical, post-approval, or sales milestones, or royalties, as we do not intend to continue to pursue the clinical development plan for ANG-3777 , which had included a Phase 3 study for CSA-AKI and a phase 4 confirmatory study in DGF.. We and Vifor continue to complete the planned analyses of the results of the clinical trials announced in the fourth quarter of 2021 and discuss the future of the collaboration.
Collaboration with the University of Michigan
In 2019, we entered into a subcontractor agreement with The Regents of the University of Michigan (UM),
under which we provide funding for identification of ANG-3070-responsive disease marker profiles in rodent models, and their intersection with existing data on patients with various forms of nephrotic kidney disease, to identify potential ANG-3070-responsive patient subsets. Under this agreement we obtain access to the Nephrotic Syndrome Study Network (NEPTUNE), an integrated group of academic centers, patient support organizations and clinical resources dedicated to advancing the treatment of kidney disorders. The goal of work under this agreement, which we support through a grant from the U.S. Department of Defense, is to identify human disease and drug response profiles based upon the genes, networks and pathways that correlate with the therapeutic activity of ANG-3070 in primary FSGS and other fibrotic renal diseases. Weprograms are obligated to provide to UM up to a total of $520,000 over the course of the project. We have an option to license and commercialize intellectual property generated during the term of the agreement that is solely owned by UM under commercially reasonable terms. See Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations. On March 21, 2022, Angion provided written notice to UM of its intention to terminate the subcontractor agreement as Angion believes the work under the related U.S. Department of Defense grantlikely to be complete.
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License Agreement with Ohr Cosmetics LLC.
In November 2013, we granted Ohr an exclusive worldwide license, with the right to sublicense, under our patent rights covering one of our CYP26 inhibitors, for the use in treating conditions of the skin or hair. Sublicensees may not grant further sublicenses under our patent rights other than to affiliates of such sublicenseesproduct safety, efficacy, convenience and entities with which sublicensees are collaborating for the research, development, manufacture and commercialization of the products. Ohr will pay us a royalty at a rate in the low single digits on gross revenue of products incorporating ANG‑3522, and milestone payments potentially totaling up to $9.0 million based on achievement of sales milestones. Royalties and milestone payments will be paid until the later of 15 years from the first commercial sale of a licensed product or the last to expire licensed patent rights. The royalty rate is subject to adjustments under certain circumstances. The Ohr License represents a related-party transaction, as discussed in Note 15 in this Annual Report on Form 10-K below, and we believe the Ohr License was made on terms no less favorable to us than those we could obtain from unaffiliated third parties. No revenue from this license agreement was recognized during the year ended December 31, 2021.treatment cost.
Government Regulation and Product Approval
The FDA and other regulatoryGovernment authorities in the United States, at the federal, state, and local levels, as well aslevel, and in foreignother countries, extensively regulate, among other things, the research, development, testing, manufacture,approval, manufacturing, packaging, storage, recordkeeping, approval, labeling, marketing andadvertising, promotion, distribution, post-approval monitoring and reporting, sampling, andmarketing, import, and export of drugs, such as thosebiopharmaceutical products. In addition, sponsors of biopharmaceutical products participating in Medicaid,
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Medicare, and other government health care programs are required to comply with mandatory price reporting, discount, and rebate requirements. We, along with our third-party contractors, will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we are developing.wish to conduct studies or seek approval or licensure of our product candidates. The process ofprocesses for obtaining regulatory approvals in the United States and the subsequentin foreign countries, along with compliance with appropriate federal, state, local and foreignapplicable statutes and regulations, requirerequires the expenditure of substantial time and financial resources.
U.S. DrugFDA Regulation
In the United States, the FDA regulates drugsbiologics under the Federal Food, Drug, and Cosmetic Act (“FDCA”) the Public Health Services Act (“PHSA”), and itstheir implementing regulations. The FDA approval is required before any new drug can be marketed infurther has issued a growing body of guidance documents, which, while not binding, provide the United States. Drugs are also subject to other federal, state and localagency’s current interpretation of its statutes and regulations. Failure to comply with the applicable FDA or otherU.S. requirements may subject a companyan applicant to a variety of administrative or judicial sanctions, such as FDA clinical holds, refusal to approve pending biologics license applications withdrawal(“BLAs”) or the agency's issuance of an approval, warning letters, or untitled letters,the imposition of fines, civil penalties, product recalls, product seizures, total or partial suspension of production or distribution, injunctions fines, civil penaltiesand/or criminal prosecution brought by the FDA and criminal prosecution.the U.S. Department of Justice or other governmental entities.
The process required by the FDA before product candidates may be marketed in the United States generally involves the following:
completion of preclinical (or nonclinical) laboratory tests and animalformulation studies all performed in accordancecompliance with the FDA's Good Laboratory Practice (GLP)FDA’s good laboratory practice (“GLP”) regulations;
submission to the FDA of an investigational new drugInvestigation New Drug application (IND)(“IND”) which must become effective before human clinical studiestrials may begin and must be updated annually or when significant changes are made;at United States clinical trial sites;
approval by an independent institutional review board (IRB) representing(“IRB”) for each clinical site, or centrally, before a clinical studyeach trial may be initiated;
performance of adequate and well-controlled human clinical trials to establish the product candidate’s safety, purity, potency, and efficacy for its intended use, performed in accordance with good clinical practice (GCP)(“GCP”) as well as IND regulations and other clinical-trial related regulations;
development of manufacturing processes to establish the safety and efficacy ofensure the product candidate for each proposed indication;candidate’s identity, strength, quality, purity, and potency in compliance with current good manufacturing practice (“cGMP”) regulations;
preparation of and submission to the FDA of a new drug application (NDA);BLA;
satisfactory completion of an FDA advisory committee review, if applicable;
a determination by the FDA within 60 days of its receipt of an NDA to file the application for review;
satisfactory completion of an FDA pre-approval inspection of the manufacturing facility(ies) where the product is manufactured to assess compliance with current good manufacturing practice (cGMP) regulations, and of selected clinical investigation sites to assess compliance with GCP; and
FDA review and approval of an NDAthe BLA to permit commercial marketing of the product for its particular labeled uses in the United States.indications for use.
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Preclinical Studies and Clinical StudiesIND Submission
The preclinical and clinical testing and approval process can takeof product candidates requires substantial time, effort, and financial resources. Satisfaction of FDA pre-market approval requirements typically takes many years and the actual time required to obtain approval, if any, may vary substantially based upon the type, complexity, and novelty of the product or condition being treated.
disease. Preclinical testsstudies include laboratory evaluation of chemistry, pharmacology, toxicity, and product chemistry, formulation, and toxicity, as well asmay involve in vitro testing or in vivo animal studies to assess the characteristicspotential for toxicity, adverse events, and potentialother safety and efficacycharacteristics of the product.product candidate, and in some cases to establish a rationale for therapeutic use. Such studies must generally be conducted in accordance with FDA GLP regulations. The conduct of preclinicalConsolidated Appropriations Act for 2023, signed into law on December 29, 2022, (P.L. 117-328) amended the FDCA and the PHSA to specify that nonclinical testing for drugs and biologics may, but is not required to, include in vivo animal studies. According to the amended language, a sponsor may fulfill nonclinical testing requirements by completing various in vitro assays (e.g., cell-based assays, organ chips, or microphysiological systems), in silico studies (i.e., computer modeling), other human or nonhuman biology-based tests (e.g., bioprinting), or in vivo animal studies.
Prior to commencing the first clinical trial at a U.S. investigational site with a product candidate, an IND sponsor must comply with federal regulations and requirements, including GLP. Thesubmit the results of preclinical testing are submittedthe nonclinical tests, together with manufacturing information, analytical data, any available clinical data or relevant scientific literature (including data from clinical trials conducted outside of the United States), and proposed clinical study protocols among other things, to the FDA as part of an IND. An IND alongis a request from a clinical study sponsor to obtain authorization from the FDA to administer an investigational drug or biologic product to humans in accordance with other information, including information about product chemistry, manufacturing and controls and any available human data or literaturea specific clinical trial protocol. Some long-term nonclinical testing to support use
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further establish the safety profile of the product in humans. Long-term preclinical tests, suchcandidate, as animal tests of reproductive toxicitywell as manufacturing process development and carcinogenicity, may continueproduct quality evaluation, continues after the IND is submitted.
The central focus of an IND submission is on the general investigational plan and the protocol(s) for human studies. An IND must become effective before human clinical trials may begin. An IND willgoes into effect upon notification by the FDA or automatically become effective 30 days after receipt by the FDA, unless before that time the FDA, raiseswithin the 30–day-time period, notifies the applicant of safety concerns or questions related to theone or more proposed clinical studies.trials and places the trial on a clinical hold. In such a case, the IND may be placed on clinical hold and the IND sponsor and the FDA must resolve anyall outstanding concerns or questions posed by the FDA before the clinical studiestrial can begin. Clinical holds also may be imposed by the FDA at any time before or during clinical trials due to safety concerns or non-compliance with applicable regulations. As a result, submission of an IND may not result in FDA authorization to commence a clinical trial. A separate submission to an existing IND must also be made for each successive clinical trial conducted during product development along with any subsequent changes to the investigational plan.development.
Clinical studiesTrials
Clinical trials involve the administration of the investigational new drugproduct to human subjects under the supervision of qualified investigators in accordance with GCPs,federal regulations and GCP requirements, which include the requirement that all research subjects provide their informed consent in writing for their participation in eachany clinical study.trial, as well as review and approval of the trial by an IRB. Investigators must also provide certain information to the clinical trial sponsors to allow the sponsors to make certain financial disclosures to the FDA. Clinical studiestrials are conducted under protocols detailing, among other things, the objectives of the study,trial, the trial procedures, the parameters to be used in monitoring safety, and the efficacyeffectiveness criteria to be evaluated.evaluated, and a statistical analysis plan. A protocol for each clinical studytrial, and any subsequent protocol amendments, must be submitted to the FDA as part of the IND. Additionally, approvalIn addition, an IRB at each site participating in the clinical trial, or a central IRB, must review and approve the plan for any clinical trial, informed consent forms, and communications to trial subjects before a trial commences at that site. An IRB considers, among other things, whether the risks to individuals participating in the trials are minimized and are reasonable in relation to anticipated benefits, and whether the planned human subject protections are adequate. The IRB must continue to oversee the clinical trial while it is being conducted. If a product candidate is being investigated for multiple intended indications, separate INDs may also be obtained from eachrequired. Status reports summarizing the progress of the clinical study site's IRB before a study maytrials must be initiatedsubmitted at least annually to the site,FDA and the IRB must monitor the study until completed. Each year, sponsors must submit an annual progress report to FDA detailing the status of the clinical trial(s) under an IND, and sponsors must timely report to FDA anymore frequently if suspected unexpected serious and unexpected adverse reactions any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol, or anyoccur, findings from other preclinical or clinical studies that suggest a significant risk into humans exposed to the drug. investigational product, findings from animal or in vitro testing suggest a significant risk for human subjects, or other significant safety information is found.
The FDA may order the temporary, or permanent, discontinuation of a clinical trial at any time, or impose other sanctions on various grounds, including if the agency believes that the clinical trial either is not being conducted in accordance with regulatory requirements or presents an unacceptable risk to the clinical trial subjects. An IRB may also require the clinical trial at the site to be halted, either temporarily or permanently, for failure to comply with the IRB’s requirements or if the trial poses an unexpected serious harm to subjects. The FDA or an IRB may also impose conditions on the conduct of a clinical trial. Clinical trial sponsors may also choose to discontinue clinical trials as a result of risks to subjects, a lack of favorable results, or changing business priorities. Some clinical trials also include oversight by an independent group of qualified experts organized by the trial sponsor, known as an independent data monitoring committee (“IDMC”) which provides authorization for whether a trial may move forward at designated check points based on review of certain data from the trial, to which only the IDMC has access, and may recommend halting the trial if it determines that there is an unacceptable safety risk for subjects or on other grounds, such as no demonstration of efficacy.
Sponsors of clinical trials of certain FDA-regulated products generally must also register and report ongoingdisclose certain clinical studies and clinical study resultstrial information to a public registries, including the websiteregistry maintained by the National Institutes of Health (“NIH”). In particular, information related to the investigational product, patient population, phase of investigation, trial sites and investigators and other aspects of the clinical trial is made public as part of the registration of the clinical trial. Competitors may use this publicly available information to gain knowledge regarding the progress of development programs. Although sponsors are also obligated to disclose the results of their clinical trials after completion, disclosure of the results may be delayed in some cases for up to two years after the date of completion of the trial. Failure to timely register a covered clinical study or to submit study results as provided for in the law can give rise to civil monetary penalties and also prevent the non-compliant party from receiving future grant funds from the federal government. The U.S. NIH, ClinicalTrials.gov.Department of Health and Human Services’ Final Rule and NIH’s complementary policy on ClinicalTrials.gov registration and reporting requirements became effective in 2017, and the government has brought enforcement actions against non-compliant clinical trial sponsors. Sponsors or distributors of investigational products for the diagnosis, monitoring, or treatment of one or more serious diseases or conditions must also have a publicly available policy on evaluating and responding to requests for expanded access requests.
ForThe manufacture of investigational biologics for the conduct of human clinical trials is subject to cGMP requirements. Investigational biologics and their therapeutic substances that are imported into the United States are also subject to regulation by the FDA. Further, the export of investigational products outside of the United States is subject to regulatory requirements of the receiving country as well as U.S. export requirements under the FDCA.
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In general, for purposes of NDABLA approval, human clinical trials are typically divided intoconducted in three or four phases. Although thesequential phases, are usually conducted sequentially, theywhich may overlap or be combined.
Phase 1.1The drugproduct candidate is initially introduced intoadministered to healthy human subjectsvolunteers and tested for safety, dosage tolerance, structure-activity relationships, mechanism of action, absorption, metabolism, distribution, and excretion. In the case of some products for severe or intolife-threatening diseases, such as cancer, especially when the product may be too inherently toxic to administer ethically to healthy volunteers, the initial human testing is often conducted in patients with the target disease or condition. These studies are designed to evaluate the safety, dosage tolerance, metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and ifIf possible, Phase 1 trials may also be used to gain early evidence onan initial indication of product effectiveness.
Phase 2.2 The drug is administered to—Studies are conducted in limited subject populations with a limited patient populationspecified disease or condition to evaluate preliminary efficacy, identify optimal dosages, dosage tolerance and optimal dosage, identifyschedule, possible adverse side effects and safety risks, and preliminarily evaluate efficacy.expanded evidence of safety. Multiple Phase 2 clinical trials may be conducted by the sponsor to obtain information prior to beginning larger and more extensive clinical trials.
Phase 3.3 The drug is administered to an—Clinical trials are undertaken with expanded patient population,subject populations, generally at geographically dispersed clinical studytrial sites, to generate enoughsufficient data to provide statistically evaluate dosage,significant evidence of clinical effectivenessefficacy and safety of the product candidate, to establish the overall benefit-risk relationshiprisk-benefit profile of the investigational product candidate, and to provide an adequate basisinformation for the labeling of the product candidate. Typically, two adequate, well-controlled trials are required by the FDA for biological product approval.
Phase 4. In Under some cases,limited circumstances, however, the FDA may approve a BLA based upon a single clinical trial plus confirmatory evidence from a post-market trial or, alternatively, a single large, robust, well-controlled multicenter trial without confirmatory evidence.
Additional kinds of data may also help to support a BLA, such as patient experience and real-world data. For appropriate indications sought through supplemental BLAs, data summaries may provide marketing application support. For genetically targeted products and variant protein targeted products intended to address an unmet medical need in one or more patient subgroups with a serious or life threatening rare disease or condition, approvalthe FDA may allow a sponsor to rely upon data and information previously developed by the sponsor or for which the sponsor has a right of reference, that was submitted previously to support an NDAapproved application for a product candidate onthat incorporates or utilizes the sponsor's agreement to conduct additional clinical studies after approval. In other cases,same or similar genetically targeted technology or a sponsorproduct that is the same or utilizes the same variant protein targeted therapeutic agent as the product that is the subject of the application.
The FDA may also require, or companies may voluntarily conduct, additional clinical studiestrials for the same indication after approval to gain more information about the drug. Sucha product is approved. These post-approval studies are typicallytrials, referred to as Phase 4 clinical studies.
Thetrials, are used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances, the FDA may mandate the IRB or the clinical study sponsor may suspend or terminateperformance of Phase 4 trials as a clinical study at any time on various grounds, including a finding that the research subjects are being exposed to an unacceptable health risk. We may also suspend or terminate a clinical study based on evolving business objectives and/or competitive climate.
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During the developmentapproval of a new drug, sponsors are given opportunities to meet with the FDA at certain points. These points may be prior to the submission of an IND, at the endBLA. The results of Phase 24 studies can confirm or refute the effectiveness of a product candidate and before an NDA is submitted. Meetings at other times may be requested. These meetings can provide an opportunity for the sponsor to share information about the data gathered to date and for the FDA to provide advice on the next phase of development. Sponsors typically use the meeting at the end of Phase 2 to discuss their Phase 2 clinical results and present their plans for the pivotal Phase 3 clinical trial that they believe will support the approval of the new drug.important safety information.
Concurrent with clinical trials, companies mayusually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the product candidate and mustas well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, manufacturers must includedevelop methods for testing the identity, strength, quality, potency, and purity of the final product. Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.
SubmissionIn the Consolidated Appropriations Act for 2023, Congress amended the FDCA to require sponsors of an NDAa Phase 3 clinical trial, or other “pivotal study” of a new medical product to support marketing authorization, to submit a diversity action plan for such clinical trial. The action plan must include the sponsor’s diversity goals for enrollment, as well as a rationale for the goals and a description of how the sponsor will meet them. A sponsor must submit a diversity action plan to FDA by the time the sponsor submits the trial protocol to the agency for review. The FDA may grant a waiver for some or all of the requirements for a diversity action plan. It is unknown at this time how the diversity action plan may affect Phase 3 trial planning and timing or what specific information FDA will expect in such plans, but if FDA objects to a sponsor’s diversity action plan and requires the sponsor to amend the plan or take other actions, it may delay trial initiation.
Marketing Application Submission, Review by the FDA, and Marketing Approval
Assuming successful completion of allthe required clinical and preclinical testing in accordance with all applicable regulatory requirements, the results of product development, including chemistry, manufacture, and testingcontrols information, nonclinical studies, and clinical trial results, including negative or ambiguous results as well as positive
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findings, are all submitted to the FDA, inalong with the formproposed labeling, as part of an NDAa BLA requesting approval to market the product for one or more indications. The submissionA BLA must contain sufficient evidence of an NDA requires payment of a substantial application user fee to the FDA, unless a waiverbiological product candidate’s safety, purity, potency and efficacy for its proposed indication or exemption applies.
An NDA must include all relevant data available from pertinent preclinical and clinical studies, including negative or ambiguous results as well as positive findings, together with detailed information relating to the product's chemistry, manufacturing, controls and proposed labeling, among other things.indications. Data canmay come from company-sponsored clinical studiestrials intended to test the safety and effectivenessefficacy of a product’s use of a product, or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and effectivenessefficacy of the investigational product to the satisfaction of the FDA. The testing and approval processes require substantial time and effort and there can be no assurance that the FDA will accept the BLA for filing and, even if filed, that any approval will be granted on a timely basis, if at all.
Under the Prescription Drug User Fee Act, as amended(“PDUFA”), each BLA submission is subject to a substantial application user fee, and the sponsor of an approved BLA is also subject to an annual program fee. The FDA adjusts the PDUFA user fees on an annual basis. The application user fee must be paid at the time of the first submission of the application, even if the application is being submitted on a rolling basis. Fee waivers or reductions are available in certain circumstances, including a waiver of the application fee for the first application filed by a small business. Product candidates that are designated as orphan products are also not subject to application user fees, unless the application also includes a non-orphan indication.
In addition, under the Pediatric Research Equity Act (“PREA”), a BLA or supplement to a BLA for a new active ingredient, indication, dosage form, dosage regimen, or route of administration, must contain data that are adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data requirements. A sponsor who is planning to submit a marketing application for a product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration must submit an initial Pediatric Study Plan (“PSP”) within 60 days of an end-of-Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 clinical trial. The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including trial objectives and design, age groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information. The FDA and the sponsor must reach an agreement on the PSP. A sponsor can submit amendments to an agreed upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from preclinical studies, early-phase clinical trials or other clinical development programs. Orphan products are exempt from the PREA requirements.
The FDA Reauthorization Act of 2017 introduced a provision regarding required pediatric studies. Under this statute, for product candidates intended for the treatment of adult cancer which are directed at molecular targets that the FDA determines to be substantially relevant to the growth or progression of pediatric cancer, original application sponsors must submit, with the marketing application, reports from molecularly targeted pediatric cancer investigations designed to yield clinically meaningful pediatric study data, gathered using appropriate formulations for each applicable age group, to inform potential pediatric labeling. The FDA may, on its own initiative or at the request of the applicant, grant deferrals or waivers of some or all of this data, as above. Unlike PREA, orphan products are not exempt from this requirement.
The FDA also may require submission of a risk evaluation and mitigation strategy (“REMS”) if it determines that a REMS is necessary to ensure that the benefits of the product candidate outweigh the risks and to assure safe use of the biological product. The REMS plan could include medication guides, physician communication plans, assessment plans and/or elements to assure safe use, such as restricted distribution methods, patient registries, or other risk minimization tools. The FDA determines the requirement for a REMS, as well as the specific REMS provisions, on a case-by-case basis. If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS. The FDA will not approve a BLA without a REMS, if required. An assessment of the REMS must also be conducted at set intervals. Following product approval, a REMS may also be required by the FDA if new safety information is discovered and the FDA determines that a REMS is necessary to ensure that the benefits of the product outweigh the risks.
Once the FDA receives a marketing application for a biologic, it has 60 days from its receipt of an NDAto review the BLA to determine whether the application will be accepted for filing based on the agency's threshold determination thatif it is sufficientlysubstantially complete to permit a substantive review.review, before it accepts the application for filing. The FDA may request additional information rather than accept an application for filing. In this event, the application must be resubmitted with the additional information and is subject to payment of additional user fees.information. The resubmitted application is also subject to review before the FDA accepts it for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review.
Under the Prescription Drug User Fee Act (PDUFA)goals and policies agreed to by the FDA under PDUFA, the FDA has agreed to certain performance goals inset the review goal of NDAs throughcompleting its review of 90% of BLAs within ten months of the filing date for a two-tiered classification system, standard application and within six months of the filing date for an application with priority review. For all original BLAs, the ten and six-month time
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periods run from the filing date; for all other submissions, including resubmissions, efficacy supplements and other supplements, the FDA’s stated review time periods, ranging from two to ten months, run from the submission date. This review goal is referred to as the PDUFA date. The PDUFA date is only a goal, and Priority Review. Priority Review designationit is givennot uncommon for FDA review of a BLA to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. According toextend beyond the PDUFA performance goals,date. The review process and the PDUFA date may also be extended if the FDA endeavors to review applications subject to standard review within ten to twelve months, whereasrequests, or the FDA's goal is to review Priority Review applications within six to eight months, depending on whethersponsor otherwise provides, substantial additional information or clarification regarding the drug is a new molecular entity.submission.
The FDA may also refer certain applications to an advisory committee. Before approving a product candidate for novel drug productswhich no active ingredient has previously been approved by the FDA, the FDA must either refer that product candidate to an external advisory committee or drug products which present difficult questionsprovide in an action letter a summary of safety or efficacythe reasons why the FDA did not refer the product candidate to an advisory committee. The FDA may also refer other product candidates to an advisory committee forif FDA believes that the advisory committee’s expertise would be beneficial. An advisory committee is typically a panel that includes clinicians and other experts, which review, evaluationevaluate, and make a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making product approval decisions.
The FDA reviews a BLA to determine, among other things, whether a product candidate meets the agency’s approval standards, such as whether the application includes sufficient evidence that the product candidate is safe and effective for the proposed indications, and whether the manufacturing methods and controls are adequate to assure and preserve the product’s identity, strength, quality, potency, and purity. As part of its review, the FDA likely will re-analyze the clinical trial data, which could result in extensive discussions between the FDA and the applicant during the review process. Before approving an NDA,a marketing application, the FDA typically will inspect the facility or facilities where the product is manufactured.manufactured, referred to as a pre-approval inspection. The FDA will not approve an application unless it determines that the manufacturing processes and facilities, including contract manufacturers and subcontractors, are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving a marketing application the FDA will typicallymay inspect one or more clinical trial sites to assure that relevant study data was obtained in compliance with applicable IND trial requirements and GCP. To assure cGMP and GCP requirements.compliance, an applicant must incur significant expenditure of time, money and effort in the areas of training, record keeping, production, and quality control.
After evaluating the FDA evaluatesmarketing application and all related information, including the NDAadvisory committee recommendation, if any, and conducts inspections ofinspection reports regarding the manufacturing facilities itand clinical trial sites, the FDA may issue an approval letter, or, in some cases, a complete response letter.Complete Response Letter (“CRL”). A complete response letterCRL indicates that the review cycle of the application is complete and the application iswill not ready for approval.be approved in its present form, and it describes all of the specific deficiencies that the FDA identified. A complete response letterCRL generally outlinescontains a statement of specific conditions that must be met in order to secure final approval of the deficiencies in the submissionmarketing application and may require substantial additional testingclinical or information in orderpreclinical testing for the FDA to reconsider the application. The deficiencies identified may be minor, for example, requiring labeling changes; or major, for example, requiring additional Phase 3 clinical trials. If a CRL is issued, the applicant may either: resubmit the marketing application, addressing all of the deficiencies identified in the letter; withdraw the application; or request an opportunity for a hearing. The FDA has the goal of reviewing 90% of application resubmissions in either two or six months of the resubmission date, depending on the type of information included. Even with submission of this additional information, the FDA ultimately may ultimately decide that anthe application does not satisfy the regulatory criteria for approval. If orand when the deficienciesthose conditions have been addressedmet to the FDA'sFDA’s satisfaction, in a resubmission of the application, the FDA willmay issue an approval letter. An approval letter authorizes commercial marketing of the drugproduct with specific prescribing information for specific indications.
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As a condition of NDA approval,Even if the FDA approves a product, it may require a Risk Evaluation and Mitigation Strategy (REMS) program to help ensure thatlimit the benefitsapproved indications or populations for use of the drug outweigh its risks. Ifproduct, require that contraindications, warnings, or precautions be included in the FDA determinesproduct labeling, including a REMS program is necessary during review of the application, the drug sponsor must agreeboxed warning, require that post-approval studies, including Phase 4 clinical trials, be conducted to the REMS plan at the time of approval. A REMS program may be required to include various elements, such asfurther assess a medication guide or patient package insert, a communication plan to educate healthcare providers of the drug's risks, or other elements to assure safe use, such as limitations on who may prescribe or dispense the drug, dispensing only under certain circumstances, special monitoringproduct’s safety and the use of patient registries. In addition, all REMS programs must include a timetable to periodically assess the strategy following implementation.
Further, productefficacy after approval, may require substantial post-approval testing and surveillance programs to monitor the drug's safetyproduct after commercialization, or impose other conditions, including distribution restrictions or other risk management mechanisms under a REMS which can materially affect the potential market and efficacy,profitability of the product. The FDA also may not approve label statements that are necessary for successful commercialization and the FDA has the authority tomarketing or may prevent or limit further marketing of a product based on the results of these post-marketing trials or surveillance programs. Once granted,
After approval, some types of changes to the approved product, approvalssuch as adding new indications, manufacturing changes, and additional labeling claims, are subject to further testing requirements and FDA review and approval. The FDA may be withdrawnalso withdraw the product approval if compliance with regulatory standards is not maintained or if problems are identified following initial marketing. Moreover, changes tooccur after the conditions established in an approved application, including changes in indications,product reaches the marketplace. Further, should new safety information arise, additional testing, product labeling, or manufacturing processes or facilities may require submission and FDA approval of a new NDA or NDA supplement before the changes can be implemented. An NDA supplement for a new indication typically requires clinical data similar to that supporting the original approval, and the FDA uses similar procedures in reviewing supplements as it does in reviewing original applications.
Expedited Development and Review Programs
The FDA offers a number of expedited development and review programs for qualifying product candidates, one or more of whichnotification may be available for our current or future products.required.
New drug products are eligible for Fast Track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition. Fast Track designation applies to the combination of the product and the specific indication for which it is being studied. The sponsor of a Fast Track product has opportunities for frequent interactions with the review team during product development and, once an NDA is submitted, the product may be eligible for Priority Review. A Fast Track product may also be eligible for rolling review, where the FDA may consider for review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA.
A product intended to treat a serious or life-threatening disease or condition may also be eligible for Breakthrough Therapy designation to expedite its development and review. A product can receive Breakthrough Therapy designation if preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. The designation includes all of the Fast Track program features, as well as more intensive FDA interaction and guidance beginning as early as Phase 1 and an organizational commitment to expedite the development and review of the product, including involvement of senior managers.
After an NDA is submitted for a product, including a product with a Fast Track designation and/or Breakthrough Therapy designation, the NDA may be eligible for other types of FDA programs intended to expedite the FDA review and approval process, such as Priority Review and accelerated approval. A product is eligible for Priority Review if it has the potential to provide a significant improvement in the treatment, diagnosis or prevention of a serious disease or condition compared to marketed products. Depending on whether a drug contains a new molecular entity, Priority Review designation means the FDA's goal is to take action on the marketing application within six to eight months of the 60-day filing date, compared with ten to twelve months under standard review.
Additionally, products studied for their safety and effectiveness in treating serious or life-threatening diseases or conditions may receive accelerated approval upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. As a condition of accelerated approval, the FDA will generally require the sponsor to perform adequate and well-controlled post-marketing clinical studies to verify and describe the anticipated effect on irreversible morbidity or mortality or other clinical benefit. In addition, the FDA currently requiresPatent Term Restoration
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Depending upon the timing, duration and specifics of FDA approval of our biological product candidates, some of our U.S. patents may be eligible for limited patent term extension. These patent term extensions permit a patent restoration term of up to five years as compensation for any patent term lost during product development and the FDA regulatory review process. However, patent term restoration cannot extend the remaining term of a conditionpatent beyond a total of 14 years from the product’s approval date. The patent term restoration period is generally one-half the time between the effective date of an IND, and the submission date of a BLA, plus the time between the submission date of a BLA and the approval of that application. Only one patent applicable to an approved biological product is eligible for acceleratedthe extension, and the extension must be applied for prior to expiration of the patent. The USPTO in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.
Biosimilars and Exclusivity
The Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) created an abbreviated approval pre-approvalpathway for biological products shown to be biosimilar to or interchangeable with an FDA-licensed reference biological product. To date, a number of promotional materials,biosimilars have been licensed under the BPCIA, and numerous biosimilars have been approved in Europe. The FDA has issued several guidance documents outlining an approach to review and approval of biosimilars.
Biosimilarity, which could adverselyrequires no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, can be demonstrated through analytical studies, animal studies, and a clinical trial or trials. There must be no difference between the reference product and a biosimilar in mechanism of action, conditions of use, route of administration, dosage form, and strength. A biosimilar product may be deemed interchangeable with the reference product if it meets the higher hurdle of demonstrating that it can be expected to produce the same clinical results as the reference product in any given patient and, for products administered multiple times to an individual, the biologic and the reference biologic may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic without such alternation or switching. Upon licensure by the FDA, an interchangeable biosimilar may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product. The FDA approved the first interchangeable biosimilars, including an interchangeable monoclonal antibody biosimilar, in 2021.
A reference biologic is granted 12 years of data exclusivity from the time of first licensure of the product, and the first approved interchangeable biological product will be granted an exclusivity period of up to one year after it is first commercially marketed. However, certain changes and supplements to an approved BLA, and subsequent applications filed by the same sponsor, manufacturer, licensor, predecessor in interest, or other related entity do not qualify for the 12-year exclusivity period. As part of the Consolidated Appropriations Act for 2023, Congress amended the PHSA in order to permit multiple interchangeable products approved on the same day to receive and benefit from this one-year exclusivity period. If pediatric studies are performed and accepted by the FDA as responsive to a written request, the 12-year exclusivity period will be extended for an additional six months. In addition, the FDA will not accept an application for a biosimilar or interchangeable product based on the reference biological product until four years after the date of first licensure of the reference product. “First licensure” typically means the initial date the particular product at issue was licensed in the United States. Date of first licensure does not include the date of licensure of (and a new period of exclusivity is not available for) a supplement for the reference product for a subsequent application filed by the same sponsor or manufacturer of the reference product (or licensor, predecessor in interest or other related entity) for a change (not including a modification to the structure of the biological product) that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device or strength or for a modification to the structure of the biological product that does not result in a change in safety, purity or potency. Therefore, one must determine whether a new product includes a modification to the structure of a previously licensed product that results in a change in safety, purity or potency to assess whether the licensure of the new product is a first licensure that triggers its own period of exclusivity. Whether a subsequent application, if approved, warrants exclusivity as the “first licensure” of a biological product is determined on a case-by-case basis with data submitted by the sponsor.
The BPCIA is complex and continues to be interpreted and implemented by the FDA. In addition, aspects of the BPCIA, some of which may impact the timingBPCIA exclusivity provisions, have also been the subject of recent litigation. As a result, the ultimate impact, implementation, and impact of the commercial launchBPCIA is subject to significant uncertainty.
Pediatric Exclusivity
Pediatric exclusivity is a type of non-patent marketing exclusivity in the product.United States and, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity or listed patents. This six-month exclusivity may be granted if a sponsor submits pediatric data that fairly respond to a written request from the FDA for such data. The data do not need to show the product to be effective in the pediatric population studied; rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the
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additional protection is granted. If reports of requested pediatric studies are submitted to and accepted by the FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity or patent protection cover the product are extended by six months. This is not a patent term extension, but it effectively extends the regulatory period during which the FDA cannot approve another application. The issuance of a written request does not require the sponsor to undertake the described studies.
Orphan DrugProduct Designation and Exclusivity
Under theThe Orphan Drug Act provides incentives for the FDAdevelopment of products for rare diseases or conditions. Specifically, sponsors may grantapply for and receive Orphan Drug designation toDesignation (“ODD”) if a drugproduct candidate is intended to treat a rare disease or condition, which is generally a disease or condition that affects feweraffecting less than 200,000 individuals in the United States, or affecting more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making the product available in the United States a drug for this type of disease or condition will be recovered from sales in the United States sales. Additionally, sponsors must present a plausible hypothesis for clinical superiority to obtain ODD if there is a product already approved by the FDA that drug.that is considered by the FDA to be the same as the already approved product and is intended for the same indication. This hypothesis for clinical superiority must be demonstrated to obtain orphan exclusivity. Orphan Drugdrug designation must be requested before submitting an NDA. Aftera marketing application for the FDA grants Orphan Drug designation, the generic identity of the therapeutic agentproduct candidate and its potential orphan use are disclosed publicly by the FDA. The Orphan Drug designation does not convey any advantage in or shorten the duration of the regulatory review orand approval process. If granted, ODD entitles the applicant to financial incentives such as opportunities for grant funding towards clinical study costs, tax advantages, and certain user-fee waivers. After the FDA grants ODD, the identity of the therapeutic agent and its potential orphan use will be disclosed publicly by the FDA; the posting will also indicate whether the drug or biologic is no longer designated as an orphan product. More than one product candidate may receive an orphan designation for the same indication.
If a product with Orphan Drug designation subsequentlycandidate receives the first FDA approval for the diseaseindication for which it has such designation,ODD, the product is generally entitled to Orphan Drug exclusive approval (or exclusivity),orphan exclusivity, which means that the FDA may not approve any other applications, including a full NDA,application to market a product containing the same drugactive moiety for the same indication for a period of seven years, except in limited circumstances, such as a showing of clinical superiority toover the product with Orphan Drugorphan exclusivity. Orphan DrugA product is clinically superior if it is safer, more effective or makes a major contribution to patient care. Thus, orphan drug exclusivity does not preventcould block the approval of one of our potential products for seven years if a competitor obtains approval of the same product, as defined by the FDA, from approving a different drug for the same disease or condition, ororphan indication and we are not able to show the clinical superiority of our product candidate. In addition, the FDA will not recognize orphan drug exclusivity if a sponsor fails to demonstrate upon approval that the product is clinically superior to a previously approved product containing the same active moiety for the same orphan condition, regardless of whether or not the previously approved product was designated an orphan drug for a different disease or condition. Among the other benefits of Orphan Drug designation are tax credits for certain research and a waiver of the application user fee.
had orphan drug exclusivity. A designated Orphan Drugproduct that has received ODD may not receive Orphan Drugorphan exclusivity if it is approved for a use that is broader than the indication for which it received the designation. Orphan designation.exclusivity does not prevent the FDA from approving a different drug or biological product for the same disease or condition, or the same product for a different disease or condition. In addition, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.
Pediatric Use and Exclusivity
Even when not pursuing a pediatric indication, underRecent court cases have challenged the Pediatric Research Equity Act an NDA or supplement thereto must contain data that is adequateFDA’s approach to assessdetermining the safety and effectivenessscope of orphan drug exclusivity; however, at this time the agency continues to apply its long-standing interpretation of the governing regulations and has stated that it does not plan to change any orphan drug productimplementing regulations.
Fast Track, Breakthrough Therapy and Priority Review Designations
The FDA is authorized to designate certain products for expedited development or review if they are intended for the claimed indications in alltreatment of serious or life-threatening diseases or conditions, and demonstrate the potential to address unmet medical needs or present a significant improvement over existing therapy. These programs include fast track designation, breakthrough therapy designation and priority review designation.
To be eligible for a fast track designation, the FDA must determine, based on the request of a sponsor, that a product candidate is intended to treat a serious or life-threatening disease or condition and demonstrates the potential to address an unmet medical need by providing a therapy where none exists or a therapy that may be potentially superior to existing therapy based on efficacy or safety factors. Fast track designation provides opportunities for more frequent interactions with the FDA review team to expedite development and review of the product. In addition, the FDA may initiate review of sections of a marketing application before the application is complete. This “rolling review” is available if the applicant provides and the FDA approves a schedule for the submission of the application sections and the sponsor pays any required user fees upon submission of the first section of the application. In some cases, a product with fast track designation may be eligible for accelerated approval or priority review if the relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for whichcriteria are met. The FDA may rescind, or the productsponsor may forfeit, fast track designation if the designation is safe and effective. Withno longer supported by data emerging from the enactmentclinical trial process.
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Under the provisions of the Food and Drug Administration Safety and Innovation Act (“FDASIA”) enacted in 2012, sponsorsa sponsor may request designation of a product candidate as a “breakthrough therapy.” A breakthrough therapy is defined as a drug or biologic that is intended, alone or in combination with one or more other drug or biologic, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. Products designated as breakthrough therapies are eligible for the same benefits described above for fast track designation, as well as intensive guidance on an efficient development program beginning as early as Phase 1 trials, and a commitment from the FDA to involve senior managers and experienced review staff in a proactive collaborative and cross-disciplinary review. Drugs or biologics designated as breakthrough therapies are also eligible for accelerated approval of their respective marketing applications.
Finally, the FDA may grant priority review designation to product candidates that are intended to treat serious conditions and, if approved, would provide significant improvements in the safety or effectiveness over existing therapies. The FDA determines at the time that the marketing application is submitted, on a case-by-case basis, whether the proposed drug or biologic represents a significant improvement in treatment, prevention or diagnosis of disease when compared with other available therapies. Significant improvement may be illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment-limiting reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, or evidence of safety and effectiveness in a new subpopulation. A priority review designation is intended to direct overall attention and resources to the evaluation of such applications, and to shorten the FDA’s goal for taking action on a marketing application from ten months to six months for an original application from the date of filing.
Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened. Furthermore, fast track designation, breakthrough therapy designation and priority review do not change the standards for approval and may not ultimately expedite the development or approval process.
Accelerated Approval
In addition, products studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval from the FDA and may be approved on the basis of adequate and well-controlled clinical trials establishing that the drug product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit. The FDA may also grant accelerated approval for such a drug or biologic when the product has an effect on an intermediate clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality (“IMM”) and that is reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. As a condition of approval, the FDA will require that a sponsor of a drug receiving accelerated approval perform post-marketing clinical trials to verify and describe the predicted effect on IMM or other clinical endpoint, and the product may be subject to expedited withdrawal procedures. Drugs and biologics granted accelerated approval must meet the same statutory standards for safety and effectiveness as those granted traditional approval.

For the purposes of accelerated approval, a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. Surrogate endpoints can often be measured more easily or more rapidly than clinical endpoints. An intermediate clinical endpoint is a measurement of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug or biologic, such as an effect on IMM. The FDA has limited experience with accelerated approvals based on intermediate clinical endpoints, but has indicated that such endpoints generally may support accelerated approval when the therapeutic effect measured by the endpoint is not itself a clinical benefit and basis for traditional approval, if there is a basis for concluding that the therapeutic effect is reasonably likely to predict the ultimate long-term clinical benefit of a drug or biologic.
The accelerated approval pathway is most often used in settings in which the course of a disease is long and an extended period of time is required to measure the intended clinical benefit of a drug or biologic, even if the effect on the surrogate or intermediate clinical endpoint occurs rapidly. For example, accelerated approval has been used extensively in the development and approval of drugs and biologics for treatment of a variety of cancers in which the goal of therapy is generally to improve survival or decrease morbidity and the duration of the typical disease course requires lengthy and sometimes large clinical trials to demonstrate a clinical or survival benefit.
The accelerated approval pathway is usually contingent on a sponsor’s agreement to conduct, in a diligent manner, additional post-approval confirmatory studies to verify and describe the drug’s clinical benefit. As a result, a product candidate approved on this basis is subject to rigorous post-marketing compliance requirements, including the completion of Phase 4 or post-approval clinical trials to establish the effect on the clinical endpoint. Failure to
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conduct required post-approval studies, or to confirm the predicted clinical benefit of the product during post-marketing studies, would allow the FDA to withdraw approval of the drug or biologic. As part of the Consolidated Appropriations Act for 2023, Congress provided FDA additional statutory authority to mitigate potential risks to patients from continued marketing of ineffective drugs or biologics previously granted accelerated approval. Under the act’s amendments to the FDCA, FDA may require the sponsor of a product granted accelerated approval to have a confirmatory trial underway prior to approval. The sponsor must also submit pediatricprogress reports on a confirmatory trial plans priorevery six months until the trial is complete, and such reports are published on FDA’s website. The amendments also give FDA the option of using expedited procedures to withdraw product approval if the assessment data. Those plans must contain an outlinesponsor’s confirmatory trial fails to verify the claimed clinical benefits of the proposed pediatric trialsproduct.
All promotional materials for product candidates being considered and approved under the sponsor plansaccelerated approval program are subject to conduct, including trial objectives and design, any deferralprior review by the FDA.
Post-approval Requirements
Any products manufactured or waiver requests, and other information required by regulation. Thedistributed pursuant to FDA must then review the information submitted, consult with the sponsor, and agree upon a final plan. The FDA or the sponsor may request an amendment to the plan at any time. The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data requirements.
Separately, in the event the FDA issues a Written Request for pediatric data relating to a drug product, an NDA sponsor who submits such data may be entitled to pediatric exclusivity. Pediatric exclusivity is another type of non-patent marketing exclusivity which, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing exclusivity.
Post-Approval Requirements
Once an NDA is approved, a product will beapprovals are subject to pervasive and continuing regulation by the FDA, including, among other things, monitoring and record-keeping requirements, relating to drug listing and registration, recordkeeping,reporting of adverse experiences with the product, periodic reporting requirements, providing the FDA with updated safety and efficacy information, product sampling and distribution adverse event reportingrequirements, as well as advertising and promotion requirements, which include, among others, standards for direct-to-consumer advertising, restrictions on promoting products for uses or in patient populations that are not described in the product’s approved uses (known as off-label uses), limitations on industry-sponsored scientific and educational activities, and requirements for promotional activities involving the Internet.
After approval, most changes to the approved product, such as adding new indications or other labeling claims are subject to prior FDA review and approval of a new BLA or a supplement, which may require the applicant to develop additional data or conduct additional pre-clinical studies and clinical trials. The FDA may also place other conditions on approvals, including the requirement for a REMS, to assure the safe use of the product. A REMS could include medication guides, physician communication plans or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products.
In addition, quality control and promotion. Drugsmanufacturing procedures must continue to conform to applicable manufacturing requirements after approval to ensure the quality and long-term stability of the product. The cGMP regulations include requirements relating to organization of personnel, buildings and facilities, equipment, control of components and drug product containers and closures, production and process controls, packaging and labeling controls, holding and distribution, laboratory controls, records and reports and returned or salvaged products. The manufacturing facilities for our product candidates must meet cGMP requirements and satisfy the FDA or comparable foreign regulatory authorities before any product is approved and our commercial products can be manufactured. We rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of our products in accordance with cGMP regulations. These third-party manufacturers must comply with cGMP regulations that require, among other things, quality control and quality assurance, the maintenance of records and documentation and the obligation to investigate and correct any deviations from cGMP. Manufacturers, including third-party manufacturers, and other entities involved in the manufacture and distribution of approved biologics are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP and other laws. Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance. Future inspections by the FDA and other regulatory agencies may be marketedidentify compliance issues at the facilities of our CMOs that may disrupt production or distribution or require substantial resources to correct. In addition, the discovery of conditions that violate these rules, including failure to conform to cGMP regulations, could result in enforcement actions, and the discovery of problems with a product after approval may result in restrictions on a product, manufacturer, or holder of an approved BLA, including, among other things, voluntary recall and regulatory sanctions as described below.
The FDA also strictly regulates marketing, labeling, advertising, and promotion of products that are placed on the market. A company can make only those claims relating to a product that are approved by the FDA. Physicians, in their independent professional medical judgment, may prescribe legally available products for unapproved indications that are not described in the product’s labeling and that differ from those tested and approved by the FDA. Biopharmaceutical companies, however, are required to promote their products only for the approved indications and in accordance with the provisions of the approved labeling. While physicians may prescribe for off-label uses, manufacturers may only promote for the approved indications and in accordance with the provisions of the approved label. However, companies may share truthful and not misleading information that is otherwise consistent with a product's FDA approved labeling. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.liability, including, but not limited to, criminal and civil penalties under the FDCA and False Claims Act, exclusion from participation in federal health care programs, mandatory compliance programs under corporate integrity agreements, suspension and debarment from government contracts, and refusal of orders under existing government contracts.
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After approval,Moreover, the Drug Supply Chain Security Act (“DSCSA”) was enacted with the aim of building an electronic system to identify and trace certain prescription drugs distributed in the United States, including most changesbiological products. The DSCSA imposes phased-in and resource-intensive obligations on biopharmaceutical manufacturers, wholesale distributors, and dispensers related to product tracking and tracing over a 10-year period which culminated in November 2023. Among the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval. There also are continuing user fee requirements under which FDA assesses an annual program fee for each product identified in an approved NDA. In addition, quality-control, drug manufacture, packaging and labeling procedures must continue to conform to cGMPs after approval. Drugof this legislation, manufacturers and certain of their subcontractors are required to register their establishmentsprovide certain information regarding the products to wholesale distributors and dispensers to which product ownership is transferred, label products with a product identifier, and keep certain records regarding the product. A manufacturer must also verify that purchasers of the manufacturer’s products are appropriately licensed. Further, under this legislation, manufacturers have product investigation, quarantine, disposition, and notification responsibilities related to counterfeit, diverted, stolen, and intentionally adulterated products that would result in serious adverse health consequences of death to humans, as well as products that are the subject of fraudulent transactions or which are otherwise unfit for distribution such that they would be reasonably likely to result in serious health consequences or death. Most recently, the FDA announced a one-year stabilization period to November 2024, giving entities subject to the DSCSA additional time to finalize interoperable tracking systems and certain state agencies. Registration withto ensure supply chain continuity.
FDA’s post-market requirements are continuously evolving and additional requirements may apply. For instance, in March 2020, the U.S. Congress passed the Coronavirus Aid, Relief, and Economic Security Act (“CARES Act”), which includes various provisions regarding FDA subjects entities to periodic unannounced and announced inspections by the FDA and these state agencies, during which the agency inspects manufacturing facilities to assess compliance with cGMPs. FDA regulations also require investigation and correction of any deviations from cGMP and imposedrug shortage reporting requirements, upon usas well as provisions regarding supply chain security, such as risk management plan requirements, and any third-party manufacturersthe promotion of supply chain redundancy and domestic manufacturing. Any changes of law may require that we modify how we conduct our business and may deciderequire additional expenditure to use. Accordingly, manufacturers must continue to expend time, money and effortensure that we are in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance.
The FDA may withdraw approval of a product if compliance with regulatory requirements is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisionssignificant regulatory actions. Such actions may include refusal to the approvedapprove pending applications, license or approval suspension or revocation, imposition of a clinical hold or termination of clinical trials, warning letters, untitled letters, modification of promotional materials or labeling, to add new safety information;provision of corrective information, imposition of post-market studies or clinical studies to assess new safety risks; orrequirements including the need for additional testing, imposition of distribution restrictions or other restrictions under a REMS, program. Other potential consequences include,product recalls, product seizures or detentions, refusal to allow imports or exports, total or partial suspension of production or distribution, FDA debarment, injunctions, fines, consent decrees, corporate integrity agreements, suspension and debarment from government contracts, and refusal of orders under existing government contracts, exclusion from participation in federal and state health care programs, restitution, disgorgement, or civil or criminal penalties, including fines and imprisonment, and adverse publicity, among other things:adverse consequences.
Additional Controls for Biologics
To help reduce the increased risk of the introduction of adventitious agents, the PHSA emphasizes the importance of manufacturing controls for products whose attributes cannot be precisely defined. The PHSA also provides authority to the FDA to immediately suspend licenses in situations where there exists a danger to public health, to prepare or procure products in the event of shortages and critical public health needs, and to authorize the creation and enforcement of regulations to prevent the introduction or spread of communicable diseases in the United States and between states.

restrictions
After a BLA is approved, the product may also be subject to official lot release as a condition of approval. As part of the manufacturing process, the manufacturer is required to perform certain tests on the marketing or manufacturing of a product, complete withdrawaleach lot of the product frombefore it is released for distribution. If the market or product recalls;
fines, warning or untitled letters or holds on post-approval clinical studies;
refusalis subject to official release by the FDA, the manufacturer submits samples of each lot of product to the FDA together with a release protocol showing the results of all of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of existing product approvals;
product seizure or detention, or refusal ofmanufacturer’s tests performed on the FDA to permit the import or export of products; or
injunctions or the imposition of civil or criminal penalties.
lot. The FDA may also require post-approval studies and clinical trials ifperform certain confirmatory tests on lots of some products before releasing the lots for distribution by the manufacturer.
In addition, the FDA finds that scientific data, including information regarding related drugs, deem it appropriate. The purpose of such studies would be to assess a known serious risk or signals of serious riskconducts laboratory research related to the drug orregulatory standards on the safety, purity, potency, and effectiveness of biological products.
Fraud and Abuse, Data Privacy and Security, and Transparency Laws and Regulations
Although we currently do not have any products on the market, our business activities and current and future arrangements with investigators, health care professionals, consultants, third-party payors and customers may be subject to identify an unexpected serious risk when available data indicate the potential for a serious risk. The FDA may also require a labeling change if it becomes aware of new safety information that it believes should be includedregulation and enforcement by numerous federal and state regulatory and law enforcement authorities in the labeling of a drug.
The Hatch-Waxman Amendments
ANDA Approval Process
The Drug Price Competition and Patent Term Restoration Act of 1984, known as the Hatch-Waxman Amendments, established abbreviated FDA approval procedures for drugs that are shownUnited States in addition to be equivalent to proprietary drugs previously approved by the FDA, throughincluding potentially the NDA process. ApprovalDepartment of Justice, the Department of Health and Human Services and its various divisions, including the Centers for Medicare and Medicaid Services (“CMS”) and the Health Resources and Services Administration, the Department of Veterans Affairs, the Department of Defense, and state and local governments. Our business activities must comply with numerous health care laws, including but not limited to, marketanti-kickback and distribute these generic equivalent drugs is obtained by filing an abbreviated new drug application (ANDA) with the FDA. An ANDA is a comprehensive submission that contains (among other things), datafalse claims laws and information pertaining to the active pharmaceutical ingredient, drug product formulation, specifications and stability of the generic drug,regulations as well as analytical methods, manufacturing process validation data privacy and quality control procedures. However, premarket applications for generic drugs are termed "abbreviated" because they generally do not include preclinical and clinical data to demonstrate safety and effectiveness. Instead, a generic applicant must demonstrate that its product is bioequivalent to a referenced proprietary drug. In certain situations, an applicant may obtain ANDA approval of a generic drug with a strength or dosage form that differs from the referenced proprietary drug pursuant to the filing and approval of an ANDA suitability petition. The FDA will approve the generic product as suitable for an ANDA application if it finds that the generic product does not raise new questions of safety and effectiveness as compared to the innovator product. A product is not eligible for ANDA approval if the FDA determines that it is not equivalent to the referenced proprietary drug or is intended for a different use and it is not otherwise subject to an approved suitability petition. However, such a product might be approved under an NDA, with supportive data from clinical trials.
505(b)(2) NDAs
Section 505(b)(2) of the FDCA, enacted as part of the Hatch-Waxman Amendments, permits the filing of an NDA where at least some of the information required for approval comes from clinical trials not conducted by or forsecurity
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the applicantlaws and regulations, which the applicant has not obtained a right of reference. Section 505(b)(2) can serve as a path to approval for modifications to previously approved drugs, such as new indications, formulations, dosage forms, or other conditions of use. If the 505(b)(2) applicant can establish that reliance on the FDA's previous findings of safety and effectiveness for the approved reference drug is scientifically appropriate, it may eliminate the need to conduct certain preclinical or clinical studies for the new product. The FDA may approve the new product for all, or some, of the label indications for which the reference drug has been approved,are described below, as well as for any new indication sought by the 505(b)(2) applicant.
Orange Book Listing
In seeking approval for a drug through an NDA, including a 505(b)(2) NDA, applicants are required to submit certain information to the FDA regarding any patents with claims covering the applicant's product or a method of using the product. Upon approval of the NDA, each of the patents is listed in the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations, known as the Orange Book. Any applicant that subsequently files an ANDA or 505(b)(2) application referencing the approved drug must certify to FDA, with respect to each patent listed for the approved drug in the Orange Book: (1) that no patent information was submitted to the FDA; (2) that such patent has expired; (3) the date on which such patent expires; or (4) that such patent is invalid or will not be infringed by the manufacture, use or sale of the drug product for which the application is submitted. This last certification is known as a "paragraph IV certification." For method of use patents, in lieu of submitting a certification, the applicant may elect to submit a "section viii statement" certifying that its proposed label does not contain (or carves out) any language regarding a patented method of use.
If an ANDA or 505(b)(2) applicant does not challenge one or more listed patents through a paragraph IV certification, the FDA will not approve the ANDA or 505(b)(2) application until all the listed patents claiming the reference product have expired.
If an ANDA or 505(b)(2) applicant provides a paragraph IV certification with its application, the applicant must send notice of the paragraph IV certification to the holder of the NDA for the reference productstate and all patent holders for the patent at issue within 20 days after the ANDA or Section 505(b)(2) application has been accepted for filing by the FDA. The NDA holderfederal consumer protection and patent owners may then initiate a patent infringement suit against the ANDA or 505(b)(2) applicant. Under the FDCA, the filing of a patent infringement suit within 45 days of the NDA holder's or patent owners' receipt of the notification regarding the paragraph IV certification automatically prevents the FDA from approving the ANDA or 505(b)(2) application until the earliest to occur of 30 months from the date the paragraph IV notice is received, the expiration of the patent, the settlement of the lawsuit or a court decision that the patent is invalid, unenforceable or not infringed. If the NDA holder or patent owners do not bring a patent infringement suit within the 45-day period, they may later bring a patent infringement suit under traditional patent law, but it will not invoke the 30-month stay of approval.
Separate from applicable patent terms and the 30-month stay of approval for paragraph IV applications, the FDA will also refrain from approving an ANDA or 505(b)(2) application until all applicable non-patent exclusivity for the reference drug has expired.
Non-Patent Exclusivity
NDA holders may be entitled to different periods of non-patent exclusivity, during which the FDA cannot approve an ANDA or 505(b)(2) application that relies on the approved drug. For example, an applicant may obtain five years of non-patent exclusivity upon NDA approval of a new chemical entity (NCE) which is a drug that contains an active moiety that has not been previously approved by the FDA in any other NDA. During the five-year period of NCE exclusivity, the FDA cannot accept any application for a product that contains the same active moiety as the approved NCE; however, the FDA can accept an ANDA or 505(b)(2) application for the same active moiety after a four-year period if such application includes a paragraph IV certification.
In addition, a non-NCE drug may qualify for a three-year period of exclusivity for a change to a previously approved product, such as a new indication or condition of use, if one or more new clinical studies (other than bioavailability or bioequivalence studies) was essential to the approval of the application and was conducted or sponsored by the applicant. In such case, the FDA is precluded from approving any ANDA or 505(b)(2) application for the protected modification until after the three-year exclusivity period has concluded. However, unlike NCE exclusivity, the FDA can accept an application and being the review process during the exclusivity period.
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Other types of non-patent exclusivity include seven-year Orphan Drug exclusivity and six-month pediatric exclusivity (each discussed above).
International Regulation
In addition to regulations in the United States, we could become subject to a variety of foreign regulations regarding development, approval, commercial sales and distribution of our products if we seek to market our product candidates in other jurisdictions. Whether or not we obtain FDA approval for a product, we must obtain the necessary approvals by the comparable regulatory authorities of foreign countries before we can commence clinical trials or marketing of the product in those countries. The approval process varies from country to country and can involve additional product testing and additional review periods, and the time may be longer or shorter than that required to obtain FDA approval. The requirements governing, among other things, the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country. Regulatory approval in one country does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country may negatively impact the regulatory process in others. If we fail to comply with applicable foreign regulatory requirements, we may be subject to fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.
Other Healthcare Laws
In addition to FDA restrictions on the marketing of pharmaceutical products, other foreign, federal and state healthcare regulatory laws restrict business practices in the pharmaceutical industry. These laws include, but are not limited to, federal and state anti-kickback, false claims, data privacy and security, and physician payment and drug pricing transparencyunfair competition laws.
The federal Anti-Kickback Statute, which regulates, among other things, marketing practices, educational programs, pricing policies, and relationships with health care providers or other entities, prohibits, among other things, any person or entity, from knowingly and willfully offering, paying, soliciting, receiving or providingreceiving any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or in return for purchasing, leasing, ordering, or arranging for or recommending the purchase, lease, or order, or the referral to another for the furnishing or arranging for the furnishing of any good, facility, item or service reimbursable in whole or in part, under Medicare, Medicaid, or other federal healthcare programs.health care programs, in whole or in part. The term "remuneration"“remuneration” has been interpreted broadly interpreted to include anything of value. The Anti-Kickback Statute has been interpreted to apply to arrangements between pharmaceutical manufacturersbiopharmaceutical industry members on the one hand and prescribers, purchasers, formulary managers, and beneficiaries on the other hand.other. There are certain statutory exceptions and regulatory safe harbors protecting some common activities from prosecution. The exceptions and safe harbors are drawn narrowly, and practices that involve remuneration that may be alleged to be intended to induce prescribing, purchases, or recommendations may be subject to scrutiny if they do not qualify for an exception or safe harbor. Failure to meet all of the requirements of a particular applicable statutory exception or regulatory safe harbor does not make the conduct per se illegal under the Anti-Kickback Statute. Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances. Several courts have interpreted the statute'sstatute’s intent requirement to mean that if any one purpose of an arrangement involving remuneration is to induce referrals of federal healthcarehealth care covered business, including purchases of products paid by federal health care programs, the statute has been violated. In addition,The Patient Protection and Affordable Care Act (” ACA”) of 2010, as amended, also modified the intent requirement under the Anti-Kickback Statute to a stricter standard, such that a person or entity does not needno longer needs to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. The majorityIn addition, the ACA also provided that a violation of states also have anti-kickback laws, which establish similar prohibitions, and in some cases may applythe federal Anti-Kickback Statute is grounds for the government or a whistleblower to assert that a claim for payment of items or services reimbursed by any third-party payor, including commercial insurers.resulting from such violation constitutes a false or fraudulent claim for purposes of the federal civil False Claims Act.
The federal civil False Claims Act (“FCA”) prohibits, among other things, any person or entity from knowingly presenting, or causing to be presented, a false fictitious or fraudulent claim for payment to, or approval by, the federal government, knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government, or knowingly making a false statement to avoid, decreaseavoiding, decreasing, or concealconcealing an obligation to pay money to the U.S. federal government. A claim includes "any“any request or demand"demand” for money or property presented to the U.S. government. The FCA has been used to assert liability on the basis of kickbacks and other improper referrals, improperly reported government pricing metrics such as Best Price or Average Manufacturer Price, improper use of Medicare provider or supplier numbers when detailing a provider of services, improper promotion of off-label uses, and allegations as to misrepresentations with respect to products, contract requirements, and services rendered. Intent to deceive is not required to establish liability under the FCA. Actions under the civil False Claims ActFCA may be brought by the Attorney Generalgovernment or asmay be brought by private individuals on behalf of the government, called “qui tam” actions. If the government decides to intervene in a qui tam action by a private individualand prevails in the namelawsuit, the individual will share in the proceeds from any fines or settlement funds. If the government declines to intervene, the individual may pursue the case alone. The FCA provides for treble damages and a civil penalty for each false claim, such as an invoice or pharmacy claim for reimbursement, which can aggregate into millions of dollars. For these reasons, since 2004, FCA lawsuits against biopharmaceutical companies have increased significantly in volume and breadth, leading to several substantial civil and criminal settlements regarding certain sales practices and promoting off label uses. FCA liability may further be imposed for known Medicare or Medicaid overpayments, for example, overpayments caused by understated rebate amounts that are not refunded within 60 days of discovering the government. Moreover, a claim including items or services resulting from a violation ofoverpayment, even if the U.S. federal Anti-Kickback Statute constitutesoverpayment was not caused by a false or fraudulent act. In addition, conviction or civil judgment for violating the FCA may result in exclusion from federal health care programs, and suspension and debarment from government contracts, and refusal of orders under existing government contracts.
The government may further prosecute conduct constituting a false claim for purposes ofunder the federal civilcriminal False Claims Act. The criminal False Claims Act prohibits the making or presenting of a claim to the government knowing such claim to be false, fictitious, or fraudulent and, unlike the False Claims Act, requires proof of intent to submit a false claim.
The civil monetary penalties statute is another potential statute under which biopharmaceutical companies may be subject to enforcement. Among other things, the civil monetary penalties statue imposes penaltiesfines against any person who is determined to have knowingly presented, or caused to be presented, a claimclaims to a federal health care program that the person knows, or should know, is for an item or service that was not provided as claimed or is false or fraudulent.
The federal Health Insurance Portability and Accountability Act of 1996 (HIPAA)(“HIPAA”) also created additional federal criminal statutes that prohibit, among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud or to obtain, by means of false or fraudulent pretenses, representations or promises, any healthcareof the money or property owned by, or under the custody or control of, a health care benefit program, includingregardless of whether the
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payor is public or private, third-party payors,in connection with the delivery or payment for health care benefits, knowingly and willfully embezzling or stealing from a healthcarehealth care benefit program, willfully obstructing a criminal investigation of a healthcarehealth care offense and knowingly and willfully falsifying, concealing, or covering up by any trick or device a material fact or making any materially false fictitious or fraudulent statementstatements in connection with the delivery of, or payment for, healthcare
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health care benefits, items, or services. Similarservices relating to health care matters. Additionally, the U.S. federal Anti-Kickback Statute,ACA amended the intent requirement of certain of these criminal statutes under HIPAA so that a person or entity does not needno longer needs to have actual knowledge of the statute, or the specific intent to violate it, in order to have committed a violation.
Under the federal Physician Payments Sunshine Act and its implementing regulations, manufacturers of biologics for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program (with certain exceptions) must make annual reports to CMS regarding payments and other transfers of value made to or at the request of covered recipients, such as, but not limited to, physicians, certain advanced non-physician health care providers, and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family. Certain payments for clinical trials are included within the ambit of this law. CMS makes the reported information publicly available.
Further, we may be subject to data privacy and security regulation by both the federal government and the states in which we conduct our business. HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH,(the “HITECH Act”) and theirits respective implementing regulations impose requirements on covered entities relating to the privacy, security, and breach reporting obligations with respect totransmission of individually identifiable health information, upon entities subject toknown as protected health information. Among other things, the law, such as health plans, healthcare clearinghousesHITECH Act, through its implementing regulations, makes HIPAA’s security standards and certain healthcare providers, known as covered entities, and their respectiveprivacy standards directly applicable to business associates, and theirdefined as a person or organization, other than a member of a covered subcontractorsentity’s workforce, that perform servicescreates, receives, maintains, or transmits protected health information on behalf of a covered entity for them that involve individually identifiable health information.a function or activity regulated by HIPAA. The HITECH Act also created new tiers of civil monetary penalties, amended HIPAA to makestrengthened the civil and criminal penalties directly applicable tothat may be imposed against covered entities, business associates, and individuals, and gave state attorneys general new authority to file civil actions for damages or injunctions in U.S. federal courts to enforce the federal HIPAA laws and seek attorneys’attorney’s fees and costs associated with pursuing federal civil actions. We are not a covered entity or a business associate under HIPAA, however, we are indirectly affected by HIPAA because the protected health information held by investigators conducting our clinical trials is subject to HIPAA and can only be used for our research consistent with HIPAA requirements imposed on those investigators.
In addition, there has been a recent trend of increasednumerous federal and state regulationlaws and regulations, including state data breach notification laws, and federal and state consumer protection laws govern the collection, use, disclosure, and protection of payments made to physicians and certain other healthcare providers. The Affordable Care Act, as amended by the Health Care Education and Reconciliation Act (Affordable Care Act), imposed, among other things, new annual reporting requirements through the Physician Payments Sunshine Act for covered manufacturers for certain payments and "transfers of value" provided to physicians (as defined by statute), certain other health care professionals, and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members. In addition, certain states require implementation of compliance programs and compliance with the pharmaceutical industry's voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, impose restrictions on marketing practices and/or require the tracking and reporting of marketing expenditures and pricing information as well as gifts, compensationhealth-related and other remuneration or itemspersonal information. For example, California enacted the California Consumer Privacy Act (“CCPA”), which took effect on January 1, 2020, and in 2020, California voters passed the California Privacy Rights Act (the “CPRA”), which became effective as of value providedJanuary 1, 2023, and significantly amends the CCPA and imposes additional data protection obligations on companies doing business in California.
Many states have also adopted laws similar to physicianseach of the above federal laws, which may be broader in scope and other healthcare professionals and entities.
Violations of fraud and abuse laws, including state anti-kickback and false claims laws, some of which apply to items or services reimbursed by any third-party payor, including commercial insurers,insurers. Certain state laws also regulate sponsors’ use of prescriber-identifiable data. Certain states also require implementation of commercial compliance programs and compliance with the pharmaceutical industry’s voluntary compliance guidelines and the applicable compliance guidance promulgated by the federal government, or otherwise restrict payments or the provision of other items of value that may be punishablemade to health care providers and other potential referral sources; impose restrictions on marketing practices; or require sponsors to track and report information related to payments, gifts, and other items of value to physicians and other health care providers. Furthermore, to distribute products commercially, we must comply with state laws requiring the registration of manufacturers and wholesale distributors of drug and biological products in a state, including, in certain states, manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of business within the state. Recently, states have enacted or are considering legislation intended to make drug prices more transparent and deter significant price increases, typically as consumer protection laws. These laws may affect our future sales, marketing, and other promotional activities by imposing administrative and compliance burdens.
If our operations are found to be in violation of any of the laws or regulations described above or any other laws that apply to us, we may be subject to penalties or other enforcement actions, including criminal and civil sanctions, including fines andsignificant civil monetary penalties, the possibility ofdamages, fines, disgorgement, imprisonment, exclusion from federal healthcareparticipation in government health care programs, including Medicare and Medicaid, disgorgement and corporate integrity agreements, suspension and debarment from government contracts and non-procurement transactions such as grants, and refusal of orders under existing government contracts, reputational harm, diminished profits and future earnings, and the curtailment or restructuring of our operations, any of which impose, among other things, rigorous operationalcould adversely affect our ability to operate our business and monitoringour results of operations. Any action against us for violation of these laws, even if we successfully defends against it, could cause us to incur significant legal expenses and divert our management’s attention from the operation of our business.
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To the extent that any of our products are sold in a foreign country, we may be subject to similar foreign laws and regulations, which may include, for instance, applicable post-marketing requirements, on companies. Similar sanctionsincluding safety surveillance, anti-fraud and penalties, as well as imprisonment, also can be imposed upon executive officersabuse laws, and employeesimplementation of such companies.corporate compliance programs and reporting of payments or transfers of value to health care professionals.
Coverage and Reimbursement Generally
SalesThe commercial success of our product candidates and our ability to commercialize any pharmaceuticalapproved product candidates successfully will depend in part on the extent to which such product will be covered bygovernmental payor programs at the federal and state levels, including Medicare and Medicaid, private health insurers, and other third-party payors such as federal, state and foreign government healthcare programs, commercial insurance and managed healthcare organizations, and the level of reimbursement for such product by third-party payors. Significant uncertainty exists as to the coverage and reimbursement status of any newly approved product. Decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a payor-by-payor basis. One third-party payor's decision to cover a particular product does not ensure that other payors will also provide coverage for the product. As a result, the coverage determination process can require manufactures to provide scientific, clinical support, and commercial support for the use of a product to each payor separately. This can be a time-consuming process, with no assurance that coverage andestablish adequate reimbursement levels for our product candidates. Government authorities, private health insurers, and other organizations generally decide which therapeutics they will pay for and establish reimbursement levels for health care. A growing trend in recent years is the containment of health care costs. Accordingly, governmental payors are increasingly trying control therapeutic prices through reimbursement restrictions, rebates, mandatory discounts, and formulary restrictions, among other strategies.
Medicare is a federal health care program administered by the federal government that covers individuals aged 65 and over as well as individuals with certain disabilities. Drugs and biologics may be covered under one or more sections of Medicare depending on the nature of the product and the conditions associated with and site of administration. For example, under Part D, Medicare beneficiaries may enroll in prescription drug plans offered by private entities which provide coverage for outpatient prescription drugs. Part D plans include both stand-alone prescription drug benefit plans and prescription drug coverage as a supplement to Medicare Advantage plans. Unlike Medicare Parts A and B, Part D coverage is not standardized. Part D prescription drug plan sponsors are not required to pay for all covered Part D drugs, and each drug plan can develop its own drug formulary that identifies which drugs it will cover and at what tier or level.
Medicare Part B covers most injectable drugs and biologics given in an in-patient setting and some products administered by a licensed medical provider in hospital outpatient departments and doctors’ offices. Medicare Part B is administered by Medicare Administrative Contractors, which generally have the responsibility of making coverage decisions. Subject to certain payment adjustments and limits, Medicare generally pays for a Part B-covered drug or biologic based on a percentage of manufacturer-reported Average Sales Price, which is regularly updated. We believe that our product candidates, which are intended to be administered by a health care professional in a clinical environment, will be applied consistently or obtained insubject to the first instance. For products administered under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because of the higher prices often associated with such drugs. Additionally, separate reimbursement for the product itself or the treatment or procedure in which the product is used may not be available, which may impact physician utilization.Medicare Part B rules.
In addition,the United States, the European Union, and other markets for our product candidates, government authorities and third-party payors are increasingly reducing reimbursements for pharmaceuticalattempting to limit or regulate the price of medical products and services. The U.S.services, particularly for new and innovative products and therapies, which often has resulted in average selling prices lower than they would otherwise be and sometimes at or below the provider’s acquisition cost. In the United States, it is also common for government and state legislatures have continued implementing cost-containment programs, including price controls,private health plans to use coverage determinations to leverage rebates from sponsors in order to reduce the plans’ net costs. These restrictions and limitations influence the purchase of health care services and products and lower the realization on coverage and reimbursement and requirements for substitutionsponsors’ sales of generic products.prescription therapeutics. Third-party payors are moredeveloping increasingly sophisticated methods of controlling health care costs. Third-party payors may limit coverage to specific therapeutic products on an approved list, or formulary, which might not include all of the FDA-approved products for a particular indication or might impose high copayment amounts to influence patient choice. Third-party payors also control costs by requiring prior authorization or imposing other dispensing restrictions before covering certain products and moreby broadening therapeutic classes to increase competition. Third-party payors are increasingly challenging the prices charged,price and examining the medical necessity and reviewing the cost effectivenesscost-effectiveness of pharmaceuticalmedical products and services, in addition to questioning their safety and efficacy. AdoptionAbsent clinical differentiators, third-party payors may treat products as therapeutically equivalent and base formulary decisions on net cost. To lower the prescription cost, sponsors frequently rebate a portion of the prescription price to the third-party payors. Recently, purchasers and third-party payors have begun to focus on value of new therapeutics and have sought agreements in which price is based on achievement of performance metrics.
Federal programs also impose price controls through mandatory ceiling prices on purchases by federal agencies and cost-containment measures,federally funded hospitals and adoptionclinics and mandatory rebates on retail pharmacy prescriptions paid by Medicaid and Tricare. By example, payment or reimbursement of more restrictive policies in jurisdictions with existing controlsprescription therapeutics by Medicaid or Medicare requires sponsors to submit certified pricing information to CMS. The Medicaid Drug Rebate statute and measures, could further limit salesstate statutes requires sponsors to calculate and report price points, which are used to determine mandatory rebate payments or negotiate supplemental rebate payments on both the state and federal level and Medicaid payment rates for certain therapeutics. For therapeutics paid under Medicare Part B, sponsors must also calculate and report their Average Sales Price, which is used to determine the Medicare Part B payment rate. Furthermore, as a condition of any product. Decreases in third-partyreceiving Medicare Part B reimbursement for any producteligible drugs or biologicals, the manufacturer is required to participate in other government health care programs, including the Medicaid Drug Rebate Program and the 340B Drug Pricing Program. The Medicaid Drug Rebate Program requires biopharmaceutical manufacturers to enter into and have in effect a decision by a third-party payor not to cover a product could reduce physician usage and patient demand fornational rebate agreement with the product.Secretary of Department of Health & Human
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Services (“DHHS”) as a condition for states to receive federal matching funds for the manufacturer’s outpatient therapeutic products furnished to Medicaid patients. Under the 340B Drug Pricing Program, the manufacturer must extend discounts to entities that participate in the program. In international markets,addition, therapeutics covered by certain government payor programs are subject to an additional inflation penalty which can substantially increase rebate payments. Certain states have also enacted laws that require that manufacturers report certain pricing information, including drug price increases. States laws may also limit the amount that prices may be increased or require negotiation of supplemental rebates for new drugs entering the market at price points determined to be high. Refusal to negotiate supplemental rebates can negatively affect market access and provider reimbursement.
Private payors often rely on the lead of the governmental payors in rendering coverage and reimbursement determinations. Therefore, achieving favorable CMS coverage and reimbursement is usually a significant gating issue for successful introduction of a new product. In addition, government programs as a condition of participation mandate fixed discounts or rebates from sponsors regardless of formulary position or utilization and may utilize mechanisms such as formulary placement to attain further price reductions, which can greatly reduce realization on the sale.
Further, the increased emphasis on managed health care in the United States and on country and regional pricing and reimbursement controls in the European Union will put additional pressure on product pricing, reimbursement, and healthcare payment systemsutilization, which may adversely affect our future product sales and results of operations. These pressures can arise from rules and practices of managed care groups, competition within therapeutic classes, judicial decisions and governmental laws and regulations related to Medicare, Medicaid, and health care reform, biopharmaceutical coverage and reimbursement policies, and pricing in general. Patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated health care costs. Sales of our product candidates will therefore depend substantially, both domestically and abroad, on the extent to which the costs of our products will be paid by health maintenance, managed care, pharmacy benefit and similar health care management organizations, or reimbursed by government health administration authorities, such as Medicare and Medicaid, private health insurers, and other third-party payors.
In addition, in some foreign countries, the proposed pricing for a drug must be approved before it may be lawfully marketed. The requirements governing drug pricing vary significantly bywidely from country and manyto country. Some countries have institutedprovide that drug products may be marketed only after a reimbursement price ceilings on specific products and therapies.has been agreed. Some countries may require the completion of additional studies that compare the cost-effectiveness of our product candidate to currently available therapies (so called health technology assessment (“HTA”)) in order to obtain reimbursement or pricing approval. For example, the European Union provides options for its member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use. A member state may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market. PharmaceuticalOther member states allow companies to fix their own prices for drug products may face competition from lower-priced products in foreign countries that have placed price controls on pharmaceutical productsbut monitor and may also compete with imported foreign products. Furthermore, therecontrol prescription volumes and issue guidance to physicians to limit prescriptions. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products. Historically, products launched in the European Union do not follow price structures of the United States, and prices generally tend to be significantly lower in the European Union.
As a result of the above, we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of our products, in addition to the costs required to obtain marketing approvals in the United States and in other jurisdictions. Our product willcandidates may not be considered medically reasonable and necessary or cost-effective, or the rebate percentages required to secure coverage may not yield an adequate margin over cost. Additionally, companies are increasingly finding it necessary to establish bridge programs to assist patient access to new therapies during protracted initial coverage determination periods.
Moreover, a payor’s decision to provide coverage for a specific indication or considered cost-effective by third-party payors in foreign or national-level systems. In the eventproduct does not imply that an adequate levelreimbursement rate will be approved or that significant price concessions will not be required to avoid restrictive conditions. High health plan co-payment requirements may result in patients refusing prescriptions or seeking alternative therapies. Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in therapeutic development. Coverage policies and third-party reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future. Legislative proposals to reform health care or reduce costs under government insurance programs may result in lower reimbursement for our products and product candidates or exclusion of our products and product candidates from coverage. The cost containment measures that health care payors and providers are instituting and any health care reform could significantly reduce our revenues from the sale of any approved product candidates. We cannot provide any assurances that we will be able to obtain and maintain third-party coverage or adequate reimbursement is not established, then even if afor our product is approved by global regulatory authorities, it may adversely affect the abilitycandidates in whole or in part.
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HealthcareHealth Care Reform Measures
In the United States and certainsome foreign jurisdictions, there have been, and we expect there will continue to be, a number ofseveral legislative and regulatory changes and proposed changes regarding the health care system that could prevent or delay marketing approval of product and therapeutic candidates, restrict or regulate post-approval activities, and affect the ability to profitably sell product and therapeutic candidates that obtain marketing approval. The FDA’s and other regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product and therapeutic candidates. If we are slow or unable to adapt to changes in existing requirements or the healthcare system. In March 2010,adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we otherwise may have obtained and we may not achieve or sustain profitability, which would adversely affect our business, prospects, financial condition and results of operations. Moreover, among policy makers and payors in the Affordable Care Act was signed into law, which substantially changedUnited States and elsewhere, there is significant interest in promoting changes in health care systems with the way healthcare is financed by both governmental and private insurersstated goals of containing health care costs, improving quality and/or expanding access.
For example, the ACA has had a significant impact on the health care industry in the United States. By way of example,The ACA expanded coverage for the Affordable Care Act increaseduninsured while at the minimum level of Medicaid rebates payable by manufacturers of brand name drugs from 15.1%same time containing overall health care costs. With regard to 23.1%; required collection of rebates for drugs paid by Medicaid managed care organizations; imposed a non-deductible annual fee on pharmaceutical manufacturers or importers who sell certain "branded prescription drugs" to specified federal government programs, implementedbiopharmaceutical products, the ACA, among other things, addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected; expanded eligibility criteria forinjected, increased the minimum Medicaid programs; createsrebates owed by manufacturers under the Medicaid Drug Rebate Program and extended the rebate program to individuals enrolled in Medicaid managed care organizations, established annual fees on manufacturers of certain branded prescription drugs, and created a new Patient-Centered Outcomes Research InstituteMedicare Part D coverage gap discount program. Additionally, the CREATES Act, which became law on December 20, 2019, aims to oversee, identify prioritiesaddress the concern articulated by both the FDA and others in the industry that some brand manufacturers have improperly restricted the distribution of their products, including by invoking the existence of a REMS for certain products, to deny generic product developers access to samples of brand products. Because generic product developers need samples to conduct certain comparative testing required by the FDA, some have attributed the inability to timely obtain samples as a cause of delay in the entry of generic products. To remedy this concern, the CREATES Act establishes a private cause of action that permits a generic product developer to sue the brand manufacturer to compel it to furnish the necessary samples on “commercially reasonable, market-based terms.” Whether and conduct comparative clinical effectiveness research, along with funding forhow generic product developments will use this new pathway, as well as the likely outcome of any legal challenges to provisions of the CREATES Act, remain highly uncertain and its potential effects on any of our future commercial products are unknown.
Legislative and regulatory changes under the ACA are possible, but it is unknown what form any such research;changes or any law would take and establishedhow or whether it may affect the biopharmaceutical industry as a Center for Medicare Innovation at CMSwhole or our business in the future. We expect that changes or additions to test innovative payment and service delivery models to lowerthe ACA, the Medicare and Medicaid spending, potentially including prescription drug spending.
Since its enactment, thereprograms, and changes stemming from other health care reform measures, especially with regard to health care access, financing or other legislation in individual states, could have been judicial, executive branch and congressional challenges to certain aspects ofa material adverse effect on the Affordable Care Act, and we expect there will be additional challenges and amendments to the Affordable Care Acthealth care industry in the future. By way of example, in 2017, Congress enacted the Tax Act, which eliminated the tax-based shared responsibility payment imposed by the Affordable Care Act on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the "individual mandate." On June 17, 2021. the U.S. Supreme Court dismissed a challenge on procedural grounds that argued the Affordable Care Act is unconstitutional in its entirety because the “individual mandate” was repealed by Congress. Thus, the Affordable Care Act will remain in effect in its current form. Further, prior to the U.S. Supreme Court ruling, on January 28, 2021, President Biden issued an executive order that initiated a special enrollment period for purposes of obtaining health insurance coverage through the Affordable Care Act marketplace. The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the Affordable Care Act. It is possible that the Affordable Care Act will be subject to judicial or congressional challenges in the future. It is also unclear how other efforts to challenge, repeal or replace the Affordable Care Act will impact the Affordable Care Act.
Other legislative changes have been proposed and adopted since the Affordable Care Act was enacted, including aggregate reductions of Medicare payments to providers of 2% per fiscal year and reduced payments to several types of Medicare providers, which will remain in effect through 2031 absent additional congressional action, with the exception of a temporary suspension from May 1, 2020 through March 31, 2022. Under current legislation, the actual reduction in Medicare payments will vary from 1% in 2022 to up to 3% in the final fiscal year of this sequester.United States.
Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several congressionalCongressional inquiries and proposed and enacted federal and state legislation designed to, among other things, to bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for pharmaceuticaldrug products. In July 2021,May 2019, DHHS issued a final rule to allow Medicare Advantage plans the option to use step therapy for Part B drugs beginning January 1, 2020. This final rule codified a DHHS policy change that was effective January 1, 2019.

More recently, in August 2022, President Biden administration released an executive order, “Promoting Competitionsigned into the law the Inflation Reduction Act of 2022 (the “IRA”). Among other things, the IRA has multiple provisions that may impact the prices of drug products that are both sold into the Medicare program and throughout the United States. Starting in 2023, a manufacturer of a drug or biological product covered by Medicare Parts B or D must pay a rebate to the federal government if the drug product’s price increases faster than the rate of inflation. This calculation is made on a drug product by drug product basis and the amount of the rebate owed to the federal government is directly dependent on the volume of a drug product that is paid for by Medicare Parts B or D. Additionally, starting in payment year 2026, CMS will negotiate drug prices annually for a select number of single-source Part D drugs without generic or biosimilar competition. CMS will also negotiate drug prices for a select number of Part B drugs starting for payment year 2028. If a drug product is selected by CMS for negotiation, it is expected that the revenue generated from such drug will decrease. CMS has begun to implement these new authorities and entered into the first set of agreements with pharmaceutical manufacturers to conduct price negotiations in October 2023. However, the IRA’s impact on the pharmaceutical industry in the American Economy,” withUnited States remains uncertain, in part because multiple provisions aimed at prescription drugs. Inlarge pharmaceutical companies and other stakeholders (e.g., the U.S. Chamber of Commerce) have initiated federal lawsuits against
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response to Biden’s executive order, on September 9, 2021, HHS released a Comprehensive PlanCMS arguing the program is unconstitutional for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue to advance these principles. No legislation or administrative actions have been finalized to implement these principles. In addition, Congress is considering drug pricing as part ofreasons, among other reform initiatives.In addition, individualcomplaints. Those lawsuits are currently ongoing.
Individual states in the United States have also become increasingly active in implementingpassed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, mechanismsdesigned to encourage importation from other countries and bulk purchasing. Furthermore, there has been increased interest by third party payorsFor example, in recent years, several states have formed prescription drug affordability boards (“PDABs”). Much like the IRA’s drug price negotiation program, these PDABs have attempted to implement upper payment limits (“UPLs”) on drugs sold in their respective states in both public and governmental authoritiescommercial health plans. For example, in reference pricing systems and publicationAugust 2023, Colorado’s PDAB announced a list of discounts and list prices.
Data Privacy and Security
Pharmaceutical manufacturers may be subjectfive prescription drugs that would undergo an affordability review. The effects of these efforts remain uncertain pending the outcomes of several federal lawsuits challenging state authority to regulate prescription drug payment limits. In December 2020, the U.S. Supreme Court held unanimously that federal and state and foreign health information privacy, security and data breach notification laws, which may governlaw does not preempt the collection, use, disclosure and protection of health-relatedstates’ ability to regulate pharmaceutical benefit managers (“PBMs”) and other personal information. Inmembers of the United States, HIPAA imposes privacy, security and breach reporting obligations with respect to individually identifiable health information upon "covered entities" (health plans, health care clearinghouses and certain health care providers),pharmaceutical supply chain, an important decision that may lead to further and their respective business associates, and their covered subcontractors that create, received, maintain or transmit protected health informationmore aggressive efforts by states in connection with providing a service for or on behalf of a covered entity. HIPAA mandates the reporting of certain breaches of health information to HHS, affected individuals and if the breach is large enough, the media. Entities that are found to be in violation of HIPAA as the result of a breach of unsecured protected health information, a complaint about privacy practices or an audit by HHS, may be subject to significant civil, criminal and administrative fines and penalties and/or additional reporting and oversight obligations if required to enter into a resolution agreement and corrective action plan with HHS to settle allegations of HIPAA non-compliance. Even when HIPAA does not apply, according tothis area. In mid-2022, the Federal Trade Commission oralso launched sweeping investigations into the FTC, failing to take appropriate steps to keep consumers' personal information secure constitutes unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade CommissionPBM industry that could lead to additional federal and state legislative or regulatory proposals targeting such entities’ operations, pharmacy networks, or financial arrangements. Significant efforts to change the PBM industry as it currently exists in the U.S. may affect the entire pharmaceutical supply chain and the business of other stakeholders, including biopharmaceutical developers like us.
We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative or executive action, either in the United States or abroad. We expect that additional state and federal health care reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for health care products and services, including any future drug products for which we secure marketing approval.
The Foreign Corrupt Practices Act 15 U.S.C § 45(a).
The FTC expects a company's data security measuresForeign Corrupt Practices Act (“FCPA”) prohibits any U.S. individual or business from paying, offering, or authorizing payment or offering of anything of value, directly or indirectly, to be reasonable and appropriate in lightany foreign official, political party, or candidate for the purpose of influencing any act or decision of the sensitivity and volume of consumer information it holds,foreign entity in order to assist the size and complexity of itsindividual or business andin obtaining or retaining business. The FCPA also obligates companies whose securities are listed in the cost of available tools to improve security and reduce vulnerabilities. Individually identifiable health information is considered sensitive data that merits stronger safeguards.
In addition, certain state laws govern the privacy and security of health information in certain circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts. FailureUnited States to comply with these laws, where applicable,accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations. Activities that violate the FCPA, even if they occur wholly outside the United States, can result in criminal and civil fines, imprisonment, disgorgement, oversight, and suspension and debarment from government contracts, and refusal of orders under existing government contracts.
European Union Drug Development
In the impositionEuropean Union (“European Union” or the “EU”), our product candidates and products, should they receive marketing authorization in the EU, will be subject to extensive regulatory requirements. As in the United States, medicinal products can be marketed only if a marketing authorization from the competent regulatory agencies has been obtained. Similar to the United States, the various phases of preclinical and clinical research in the European Union are subject to significant civil and/or criminal penaltiesregulatory controls.
In April 2014, the Clinical Trials Regulation, (EU) No 536/2014, was adopted and private litigation. For example, the CCPAit became effective on January 1, 2020,31, 2022. The Clinical Trials Regulation will be directly applicable in all of the European Union Member States (“EU Member States”), repealing the current Clinical Trials Directive 2001/20/EC. The extent to which among other things, creates new data privacy obligations for covered companies and provides new privacy rights to California residents, includingongoing clinical trials will be governed by the right to opt out of certain disclosures of their information. The CCPA also creates a private right of action with statutory damages for certain data breaches, thereby potentially increasing risks associated with a data breach. AlthoughClinical Trials Regulation will depend on when the law includes limited exceptions, including for "protected health information" maintained by a covered entityclinical trial is initiated or business associate, it may regulate or impact our processing of personal information depending on the context. Further,duration of an ongoing trial. As of January 2023, all new clinical trials must comply with the CPRAClinical Trials Regulation. In addition, any clinical trial that was recently voted into law by California residents. The CPRA significantly amends the CCPA, and imposes additional data protection obligations on covered companies doing business in California, including additional consumer rights processes and opt outs for certain usesalready under way as of sensitive data. It also creates a new California data protection agency specifically tasked to enforce the law, which would likely result in increased regulatory scrutiny of California businesses in the areas of data protection and security. The substantive requirements for businesses subject to the CPRA will go into effect on January 1, 2023 and become enforceablecontinues for more than three years from the day on July 1, 2023.which the Clinical Trials Regulation becomes applicable (i.e., January 31, 2025), the Clinical Trials Regulation will at that time begin to apply to the clinical trial.
The Clinical Trials Regulation aims to simplify and streamline the approval of clinical trials in the European Union. The main characteristics of the regulation include: a streamlined application procedure via a single entry point, the “EU portal” or Clinical Trial Information System (“CTIS”); a single set of documents to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors; and a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts. Part I is assessed by the competent authorities of all EU Member States in which an application for authorization of a clinical trial has been submitted (Member States concerned). Part II is assessed separately by each EU Member State concerned. Strict deadlines have been established for the assessment of clinical trial applications. The role of the relevant
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ethics committees in the assessment procedure will continue to be governed by the national law of the concerned EU Member State.
To obtain a marketing authorization of a medicinal product in the European Union, we may submit marketing authorization applications (“MAA”) either under the so-called centralized or national authorization procedures. Before granting the marketing authorization under any such procedures, described below, the EMA or the competent authorities of the individual member states make an assessment of the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy.
Centralized procedure
The centralized procedure provides for the grant of a single marketing authorization following a favorable opinion by the European Medicines Agency (“EMA”) that is valid in all EU Member States, as well as Iceland, Liechtenstein and Norway. The centralized procedure is compulsory for medicines produced by specified biotechnological processes, products designated as orphan medicinal products, advanced-therapy medicines (such as gene-therapy, somatic cell-therapy or tissue-engineered medicines) and products with a new active substance indicated for the treatment of specified diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative disorders or autoimmune diseases and other immune dysfunctions and viral diseases. The centralized procedure is optional for products that represent a significant therapeutic, scientific or technical innovation, or whose authorization would be in the interest of public health. Under the centralized procedure the maximum timeframe for the evaluation of an MAA by the EMA is 210 days, excluding clock stops, when additional written or oral information is to be provided by the applicant in response to questions asked by the Committee for Medicinal Products for Human Use (“CHMP”). Accelerated assessment might be granted by the CHMP in exceptional cases, when a medicinal product is expected to be of a major public health interest, particularly from the point of view of therapeutic innovation. The timeframe for the evaluation of an MAA under the accelerated assessment procedure is 150 days, excluding stop-clocks.
National authorization procedures
There are also two other possible routes to authorize medicinal products in several European Union countries, which are available for investigational medicinal products that fall outside the scope of the centralized procedure:
Decentralized procedure. Using the decentralized procedure, an applicant may apply for simultaneous authorization in more than one EU Member State of medicinal products that have not yet been authorized in any EU Member State and that do not fall within the mandatory scope of the centralized procedure.
Mutual recognition procedure. In Europe, the GDPR went into effectmutual recognition procedure, a medicine is first authorized in May 2018, and imposes strict requirements forone EU Member State, in accordance with the national procedures of that country. Following this, further marketing authorizations may be sought from other EU Member States in a procedure whereby the countries concerned agree to recognize the validity of the original, national marketing authorization.
European Data Collection

The collection, use, disclosure, transfer or other processing theof personal data, ofincluding personal health data, subjects withinin the EU is governed by the General Data Protection Regulation (“GDPR”). The GDPR applies to any company established in the European Economic Area (“EEA”) and to companies established outside the United Kingdom. CompaniesEEA that must complyprocess personal data in connection with the GDPR face increased compliance obligations and risk, including more robust regulatory enforcementoffering of goods or services to data subjects in the EEA or the monitoring of the behavior of data subjects in the EEA. The GDPR establishes stringent requirements applicable to the processing of personal data, including strict requirements relating to the validity of consent of data subjects, expanded disclosures about how personal data is used, requirements to conduct data protection impact assessments for “high risk” processing, limitations on retention of personal data, special provisions affording greater protection to and requiring additional compliance measures for “special categories of personal data” including health and genetic information of data subjects, mandatory data breach notification (in certain circumstances), “privacy by design” requirements, and potential finesdirect obligations on service providers acting as processors.

The GDPR also prohibits the international transfer of personal data from the EEA to “non-adequate” countries outside of the EEA unless a valid data transfer mechanism has been put in place to safeguard the personal data, such as the Standard Contractual Clauses or certification under the newly-adopted Data Privacy Framework.

The GDPR also enhances enforcement authority and imposes large penalties for noncompliance, including the potential for fines of up to €20 million or 4% of the annual global revenues of the noncompliant company,infringer, whichever is greater. Additionally, the GDPR confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR.
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United Kingdom Regulation

As of January 1, 2021, EU law no longer directly applies in the United Kingdom (“United Kingdom” or the “UK”). The United Kingdom has adopted existing EU medicines regulation as standalone UK legislation with some amendments to reflect procedural and other requirements with respect to marketing authorizations and other regulatory provisions.

In order to market medicines in the United Kingdom, manufacturers must hold a UK authorization. On January 1, 2021, all EU marketing authorizations were converted to UK marketing authorizations subject to a manufacturer opt-out. UK medicines legislation is subject to future regulatory change under the Medicines and Medical Devices Act 2021, which sets out a framework for the adoption of medicines regulation. Guidance issued by the Medicines and Healthcare products Regulatory Agency (“MHRA”) states that the United Kingdom will have the power to take into account marketing authorizations made under the EU decentralized and mutual recognition procedures. In addition, the MHRA’s guidance has been updated to refer to UK-specific licensing procedures including routes of evaluation for novel and biotechnological products.

In Northern Ireland, however, EU central marketing applications will continue to apply.
The Trade and Cooperation Agreement between the EU and the United Kingdom contains an Annex in relation to medicinal products with the objective of facilitating availability of medicines, promotion of public health and consumer protection in respect of medicinal products. The Annex provides for mutual recognition of cGMP inspections and certificates, meaning that manufacturing facilities do not need to undergo duplicate inspections for the two markets. The Annex establishes a Working Group on Medicinal Products to deal with matters under the Trade and Cooperation Agreement, facilitate co-operation and for the carrying out of technical discussions. It is expected that further bilateral discussions will continue with respect to regulatory areas not the subject of the Trade and Cooperation Agreement, including pharmacovigilance. The Trade and Cooperation Agreement also does not include reciprocal arrangements for the recognition of batch testing certification. However, the United Kingdom has listed approved countries, including the EEA which will enable UK importers and wholesales to recognize certain certification and regulatory standards. The European Commission has not adopted such recognition procedures.

Relatedly, following the United Kingdom'sKingdom’s withdrawal from the European Economic Area andEU, the European Union, andGDPR’s requirements have been implemented in the expiry ofUnited Kingdom (referred to as the transition period, companies will have to comply with“UK GDPR”). The UK GDPR sits alongside the GDPR andamended UK Data Protection Act 2018 which implements certain derogations in the EU GDPR as incorporated into United Kingdom national law,law. Under the latter regime havingUK GDPR, companies not established in the ability to separately fine upUnited Kingdom but who process personal data in relation to the greateroffering of goods or services to individuals in the United Kingdom, or to monitor their behavior will be subject to the UK GDPR – the requirements of which are (at this time) largely aligned with those under the EU GDPR and as such, may lead to similar compliance and operational costs with potential fines of up to £17.5 million or 4% of global turnover. The relationship betweenIn June 2021, the European Commission issued a decision, valid for four years from its entry into force, that the United Kingdom ensures an adequate level of protection for personal data transferred under the EU GDPR from the EU to the United Kingdom.
Rest of the World Regulation
For other countries outside of the EU and the European UnionUnited States, such as countries in relationEastern Europe, Latin America or Asia, the requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to certain aspectscountry. Additionally, clinical trials to support applications for marketing authorization in such jurisdictions must be conducted in accordance with GCP requirements and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of dataHelsinki.
If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.
Human Capital
As of December 31, 2023, we had 32 employees, all of whom were full-time, and of whom 10 have Ph.D. or M.D. degrees, and 19 are engaged in research and development and manufacturing activities. We do not have any employees represented by a labor union or covered under a collective bargaining agreement.
Talent Acquisition and Retention
We are committed to pioneering the development of immunotherapies for patients with limited treatment options and poor outcomes suffering from cancer and infectious disease. To that end, we recognize that our industry is specialized and dynamic, and a significant aspect of our success is our continued ability to execute our human capital strategy of attracting, engaging, developing and retaining highly skilled talent. We offer competitive compensation packages including base salary, annual incentive bonuses, and long-term equity incentive awards.
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protection law remains unclear,We also offer comprehensive and robust employee benefits, such as life, disability, and health insurance, health savings and flexible spending accounts, paid time off, and a 401(k) plan. We pride ourselves on our strong company culture and initiatives aligned with our mission, vision, and values. In addition, we strive to provide a collegial atmosphere where teamwork and collaboration are emphasized and valued. We use internal and external resources to recruit highly skilled candidates for example around how data can lawfullyopen positions. It is our express intent to be transferred between each jurisdiction, which may expose us to further compliance risk.
Human Capital Resources
Asan employer of December 31, 2021, we had 71 full-time employees, who provide full time support to us,choice in our industry by providing market-competitive compensation and 23 consultants who provide part time support to us.As of March 1, 2022, we had 39 full time employees and 14 part time consultants. None of our employees are represented by a labor union or covered by collective bargaining agreementsbenefits packages and we consider our employee relations to be good. Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and additional employees. The principal purposes of our equity incentive plansbelieve we are able to attract and retain superior talent as measured by our minimal turnover rate and motivate selected employees, consultantshigh employee service tenure.
Diversity, Equity, and directors through the granting of stock-based compensation awards and cash-based performance bonus awards.
Segment InformationInclusion
We believe a diverse workforce is critical to our success. Our mission is to value differences in races, ethnicities, religions, nationalities, genders, ages, and sexual orientations, as well as education, skill sets, and experience. We have one primary business activitya set of policies explicitly setting forth our expectations for nondiscrimination and operate as one reportable segment.a harassment-free work environment. We are also focused on inclusive hiring practices, fair and equitable treatment, organizational flexibility, and training and resources. We are a proud equal opportunity employer and cultivate a highly collaborative and entrepreneurial culture.
Training and Development
We believe in encouraging employees to become lifelong learners by providing ongoing learning and leadership training opportunities. We strive to provide real-time recognition of employee performance. In addition, we have a formal annual review process to determine individual contributions that may lead to pay and equity adjustments. The annual review process also helps us identify areas where training and development may be needed.
Corporate Information
On June 1, 2023, Elicio Operating Company, Inc. (“Former Elicio”) completed a merger transaction in accordance with the terms and conditions of the Agreement and Plan of Merger and Reorganization, dated as of January 17, 2023 (the “Merger Agreement”), by and among the Delaware corporation formerly known as “Angion Biomedica Corp.” (“Angion”), Arkham Merger Sub, Inc., a wholly owned subsidiary of Angion (“Merger Sub”), and Former Elicio, pursuant to which Merger Sub merged with and into Former Elicio, with Former Elicio surviving the merger as a wholly owned subsidiary of Angion (the “Merger”). Additionally, on June 1, 2023, Angion changed its name from “Angion Biomedica Corp.” to “Elicio Therapeutics, Inc.”
We were incorporated in the State of Delaware on April 6, 1998. Our corporate operations are based in San Francisco, California, our clinical development and regulatory teams are primarily located in Boston, Massachusetts, and our discovery and research programs are based in Uniondale, New York. OurFormer Elicio each have a principal executive offices are locatedoffice at 51 Charles Lindbergh Boulevard, Uniondale, New York 11553, and our telephone number is (415) 655-4899. Our website address is www.angion.com. The information contained on, or that can be accessed through, our website will not be deemed to be incorporated by reference into and does not constitute part of this Annual Report on Form 10-K.

451 D Street, Suite 501, Boston, MA 02210.
Available Information
We are subject to the information requirements of the Securities Exchange Act of 1934, as amended, and we therefore file periodic reports, proxy statements and other informationelectronically with the SEC relating to our business, financial statements and other matters. The SEC maintains an Internet site, www.sec.gov, that contains reports, proxy statements and other information regarding issuers such as Angion Biomedica Corp.
For more information about us, including free access to our annual reports on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). The SEC maintains an Internet site that contains reports, proxy information and information statements, and other information regarding issuers that file electronically with the SEC. The address of that website is http://www.sec.gov.
We maintain a public website at https://www.elicio.com and use our website as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. Our website includes an Investors section through which we make available, free of charge, our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, Proxy Statements and Forms 3, 4 and 5 filed on behalf of directors and executive officers, as well as any amendments to those reports visitfiled or furnished pursuant to the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. The members of our Board of Directors are reflected on the signature page of this annual report on Form 10-K. We also make available on our website www.angion.com.the charters for our Board of Directors’ Audit Committee, Compensation Committee and Nominating and Corporate Governance Committee, as well as our Code of Business Conduct and Ethics, and other related materials. The information found on or accessible through our website is not incorporated into, and does not form a part of this Annual Report on Form 10-K.annual report.
Item 1A. Risk FactorsFactor
Investing in our common stocksecurities involves a high degree of risk. You should carefully consider the following risk factors set forth below as updated by our subsequent filings under the Securities Exchange Act of 1934, as amended (the “Exchange Act”), before deciding whether to purchase our securities. The risks and uncertainties we describe below are not the only ones we face. Additional risks and uncertainties not presently known to us could adversely affect our business, operating results and financial condition, as well as adversely affect the value of an investment in our securities, and the occurrence of any of these risks might cause you to lose all or part of your investment.
Summary Risk Factors
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We are subject to a number of risks that if realized could affect our business, financial condition, results of operations and cash flows. As a clinical stage biopharmaceutical company, certain elements of risk are inherent to our business. Accordingly, we encounter risks as part of the normal course of our business. Some of the more significant challenges and risks include the following:
We will require substantial additional capital to finance our operations, and a failure to obtain this necessary capital when needed, on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our research and development programs, commercialization efforts or cease operations.
We have identified conditions and events that raise substantial doubt about our ability to continue as a going concern. Our independent registered public accounting firm has included an explanatory paragraph relating to our ability to continue as a going concern in its report on our audited consolidated financial statements for the year ended December 31, 2023 included in this Annual Report on Form 10-K filed with the Securities and Exchange Commission (“SEC”).
We have incurred losses since inception, have never generated any revenue from product sales, have a limited operating history on which to assess our business, and anticipate that we will continue to incur significant losses for the foreseeable future.
We have identified material weaknesses in our internal control over financial reporting related to our control environment. If we do not remediate the material weaknesses in our internal control over financial reporting, or if we fail to establish and maintain effective internal control, we may not be able to accurately report our financial results, which may cause investors to lose confidence in our reported financial information and may lead to a decline in the market price of our stock.
Our product candidates are at an early stage of development and, except for our current clinical trials, we have not previously conducted clinical trials with our product candidates. We may not be able to effectively design and execute a clinical trial that supports marketing approval and may not successfully develop or commercialize our product candidates.
Our clinical trial results may not support approval by the U.S. Food and Drug Administration (“FDA”) or comparable foreign regulatory authorities and such failure to obtain regulatory approval of our product candidates would significantly harm our business, results of operations, and prospects.
We may be unable to use and expand our discovery engine to build a pipeline of product candidates and progress such product candidates through preclinical or clinical development, which may result in us abandoning our development efforts, or we may not be able to identify, discover, develop, or commercialize additional product candidates, which would have a material adverse effect on our business and could potentially cause us to cease operations.
Due to our limited financial and managerial resources, we may focus on research programs and product candidates we identify for specific indications and may forego or delay other opportunities that may have greater commercial potential.
There are a number of factors that can impact the enrollment of patients in our clinical trials. If we experience difficulties in enrolling patients, we could experience significant delays and we may need to abandon one or more clinical trials, or we may need to increase development costs for our product candidates which could materially impair our ability to generate revenues.
Our product candidates may cause undesirable side effects, may not achieve the desired efficacy threshold, or have other properties or characteristics that could delay or prevent their regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any.
We may form or seek strategic partnerships or collaborations or enter into additional licensing arrangements with third parties and we may not realize the benefits of such transactions or arrangements.
We rely on contract manufacturing organizations (“CMOs”) to manufacture our product candidates and perform other manufacturing-related services. If these third parties do not successfully carry out their contractual duties, meet expected timelines, or otherwise conduct the trials as required or perform and comply with regulatory requirements, we may not be able to successfully complete clinical development, obtain regulatory approval or commercialize our product candidates when expected or at all, and our business could be substantially harmed. We face significant competition, and our competitors may achieve regulatory approval before us or develop safer, more advanced or effective therapies than we might develop.
Our AMP platform is novel and any current or future product candidates may be too complex to manufacture and such complexities could lead to regulatory delays or production problems that could harm our business.
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Our success depends on our ability to obtain and maintain our intellectual property for our product candidates and their formulations.
We are substantially dependent on patents we license from the Massachusetts Institute of Technology (“MIT”) and if the licensed patent rights lack legal effect or if there is a dispute under the license agreement or changes to the scope of the agreement, it could lead to a material adverse effect on our business, financial condition, results of operations and prospects.
Even if we obtain regulatory approval for our product candidates, we will remain subject to ongoing regulatory requirements. Maintaining compliance with ongoing regulatory requirements may result in significant additional expense to us, and any failure to maintain such compliance could subject us to penalties and cause our business to suffer.
Healthcare and other legislative reform measures may have a materially negative impact on our business.
Cybersecurity incidents, loss of data and other disruptions, including from cyberattacks, could compromise sensitive information related to our business, prevent us from accessing critical information or expose us to liability, which could adversely affect our business and our reputation.
The instability of the global credit and financial markets may adversely affect our business strategy, including our ability to secure necessary and timely financings, which may impact our financial performance, stock price and development of our product candidates.
We will continue to incur significant legal, accounting and other expenses in order to comply with the laws, rules, and regulations associated with being a public company.
The above list is not exhaustive, and we face additional challenges and risks. Please carefully consider all of the information in this Annual Report on Form 10-K including our consolidated financial statements and related notes, before deciding whether to investmatters set forth in shares of our common stock. Many of the following risks and uncertainties are, and will be, exacerbated by the coronavirus disease 2019 (COVID-19) pandemic and any worsening of the global business and economic environment as a result. The occurrence of any of the adverse developments described in the following risk factors could materially and adversely harm our business, financial condition, results of operations or prospects. In that case, the trading price of our common stock could decline, and you may lose all or part of your investment.this “Risk Factors” section.
Risks RelatingRelated to Our Operating History, Financial Position and Need for Additional Capital Requirements
We are a clinical-stage biopharmaceutical company with no products approved for sale and we have not generated any product revenue to date, which makes it difficult to assess our future viability.
We are a clinical-stage biopharmaceutical company. Drug development is a highly speculative undertaking and involves a substantial degree of risk. We have not yet submitted any product candidates for approval or received approval of any product candidate by regulatory authorities in any jurisdiction, including the United States Food and Drug Administration (FDA). We do not expect to generate revenue from product sales unless we, or we or our collaborators, obtain approval and commercialize our product candidates, which we do not expect to occur for
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several years, if ever. We expect to continue to incur net losses for the foreseeable future, and we expect our expenses and operating losses to increase substantially as we advance ANG-3070 and our other product candidates through clinical and preclinical development, seek regulatory approval for ANG-3070 or any of our other product candidates, and continue to incur expenses to protect our intellectual property, maintain our general and administrative support functions, including hiring additional personnel, and incur costs associated with operating as a public company.
In addition, while we have a license agreement with Vifor Pharma relating to ANG-3777 that contemplates upfront, regulatory and commercial milestone payments as well as royalties on sales of ANG-3777, we do not intend to continue the clinical development plan for ANG-3777 set forth in the Vifor License , which had included a Phase 3 study for CSA-AKI and a Phase 4 confirmatory study in DGF. Thus, it is unlikely we will receive any substantial revenue stream from milestone or royalty payments under the license agreement.
If we are unable to enroll our clinical trials for ANG-3070 or if ANG-3070 or any of our other product candidates fail in ongoing clinical trials or do not gain regulatory approval, we may never generate revenue or become profitable.

To achieve our goals we will require substantial additional funding, for which capital may not be available to usfinance our operations, and a failure to obtain this necessary capital when needed on acceptable terms, or at all, and, if not so available, may requirecould force us to delay, limit, reduce or ceaseterminate our clinical trials or operations.
We have invested and will continue to invest a significant portion of our efforts and financial resources in research and development activities. We are currently inprograms, commercialization efforts or cease operations.
Our operations have consumed substantial amounts of cash. During the processyears ended December 31, 2023 and 2022, we incurred research and development expenses of advancing ANG-3070 through a Phase 2 dose-finding clinical trial in 100 patients with Primary Proteinuria Kidney Diseases (PPKDs), specifically FSGS$23.8 million and IgAN patients, in the United States, Georgia, Bulgaria, Lithuania, Spain and Australia, and other product candidates through preclinical and potential clinical development. Developing pharmaceutical products, including conducting preclinical studies and clinical trials, is expensive.$18.1 million, respectively. We will require substantial additional future capitalfunds to complete clinical development, including additional clinical studies, and seek regulatory approval for ANG-3070 for any indication as well as to conduct the research, clinical and regulatory activities necessary to bringsupport our other product candidates to market. Regulatory authorities in the United States and elsewhere could also require that we perform additional preclinical studies or clinical trials to receive or maintain regulatory approval of our product candidates, including ANG-3070, and our expenses would further increase beyond what we currently expect. Because successful development of our product candidates is uncertain, we are unable to estimate the actual funds we will require to complete research and development of such product candidates as well as the costs of commercializing any of our wholly-owned product candidates and those for which we retain the right to commercialize.
We estimate our current cash and cash equivalents will be sufficient to fund our operating expenses and capital expenditure requirements well into 2023. We have based our projections of operating capital requirements on assumptions that may prove to be incorrect and we may use all our available capital resources sooner than we expect. Because of the numerous risks and uncertainties associated with research, development and commercialization of biotechnology products, we are unable to estimate the exact amount of our operating capital requirements. The amount and timing of our future funding requirements will depend on many factors, including, but not limited to:
the scope, progress, results and costs of researching and developing ANG-3070 or other product candidates, and conducting preclinical studies and clinical trials;
the outcome of our ongoing and future clinical trials, including our ANG-3070 Phase 2 clinical trial in PPKD;
whether we are able to take advantage of any FDA expedited development and approval programs for any of our product candidates;
the extent to which COVID-19 may impact our business, including our clinical trials and financial condition;
the willingness of the FDA and foreign regulatory authorities to accept the results of our ongoing ANG-3070 Phase 2 clinical trial, as well as our other completed and planned clinical trials and preclinical studies and other work;
the number and characteristics of product candidates that we pursue, including our product candidates in preclinical development;
the ability of our product candidates to progress through clinical development successfully;
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our need to expand ourcontinued research and development activities, including to conduct additional clinical trials;
the anticipated costs of acquiring, licensing or investing in businesses, products, product candidatesnonclinical studies and technologies;
clinical trials, regulatory approvals and potential commercialization. Additionally, our abilityestimates on future financial needs may be based on assumptions that prove to maintain, expandbe wrong, and defend the scope of our intellectual property portfolio, including the amount and timing of any payments we may be required to make, or thatspend our available financial resources much faster than we may receive, in connection with the licensing, filing, prosecution, defense and enforcement of any patents or other intellectual property rights;
our need and ability to hire additional personnel, including management, clinical development, medical and commercial personnel;
the costs associated with being a public company, including our need to implement additional internal systems and infrastructure, including financial and reporting systems;
the costs associated with securing and establishing manufacturing capabilities, as well as those associated with packaging, warehousing and distribution; and
the economic and other terms, timing of and success of our existing licensing arrangements and any collaboration, licensing or other arrangements into which we may enter in the future and the timing and amount of payments thereunder.expect.
Until such time, if ever, that we can generate sufficient product revenue from sales of ANG-3070 or any other product candidate, if ever,and achieve profitability, we expect to seek to finance our operationsfuture cash needs through the sale of common stock in public offerings and/or private equity offerings,placements, debt financings, or through other capital sources, of capital, including licensing arrangements, partnerships and collaborations licenses, creditwith other companies or loan facilities, receipt of research contributionsother strategic transactions. We currently have no other commitments or grants, tax credits or a combination of one or moreagreements relating to any of these types of transactions and cannot be certain that additional funding sources. Adequate funding may notwill be available to us on acceptable terms, or at all. This may be particularly true if global capital markets continue to experience extreme volatility due to the COVID-19 pandemic or armed conflict. To the extent that we raise additional capital through the sale of equity, or convertible debt or other securities convertible into equity, the ownership interest of our stockholders will be or could be diluted, and the terms of these new securities may include liquidation or other preferences that adversely affect the rights of our common stockholders. Debt financing, and equity financing, if available mayat all, would likely involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures, completing acquisitions or declaring dividends. If we raise funds through additional collaborations, or other similar arrangements with third parties, we may havepaying dividends.
Furthermore, the ongoing impact of COVID-19 and geopolitical instability, including the military conflict between Russia and Ukraine, the conflicts in the Middle East, and geopolitical tensions between the United States and China, as well as the impact of macroeconomic factors could make the terms of any available financing less attractive to relinquish valuable rightsus and more dilutive to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us and/or may reduce the value of our common stock.existing stockholders. If we are unable to raise additional capital, we will have to delay, curtail or eliminate one or more of our research and development programs or cease operations. In addition, securing additional financing would require a substantial amount of time and attention from our management and may divert a disproportionate amount of their attention away from day-to-day activities, which may adversely affect our management’s ability to oversee the development of our product candidates.
Our recurring losses from operations have raised substantial doubt regarding our ability to continue as a going concern.
We believe there is substantial doubt about our ability to continue as a going concern as of the date of this Annual Report on Form 10-K. Our independent registered public accounting firm has included an explanatory paragraph
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relating to our ability to continue as a going concern in its report on our audited consolidated financial statements for the year ended December 31, 2023 included in this Annual Report on Form 10-K. This going concern opinion could materially limit our ability to raise additional funds through the issuance of new debt or equity securities or debt financingsotherwise. Future reports on our financial statements may include an explanatory paragraph with respect to our ability to continue as a going concern. We have incurred significant losses since our inception and have never been profitable, and it is possible we will never achieve profitability. We have devoted a majority of our resources to developing ELI-002, but this product candidate cannot be marketed until regulatory approvals have been obtained. Meaningful revenues will likely not be available unless ELI-002 or any of our current or future product candidates are approved by the FDA or comparable regulatory agencies in other countries and successfully marketed, either by us or a partner, an outcome which may not occur.
We believe that our cash on hand will enable us to fund our operations into the third quarter of 2024 based on our current plan. This period could be shortened if there are any significant increases in planned or actual spending on development programs or more rapid progress of development programs than anticipated. There is no assurance that financing will be available when needed to allow us to continue as a going concern. If we are unable to obtain additional capital and continue as a going concern, we might have to further scale back our operations or liquidate our assets and cease operations entirely, and the values we receive for our assets in liquidation or dissolution could be significantly lower than the values reflected in our financial statements. Our lack of capital resources and our conclusion that we may be requiredunable to continue as a going concern may materially adversely affect our share price and our ability to raise new capital or to enter into critical contractual relations with third parties.
We may be unsuccessful in raising the capital necessary to address our going concern issues, or if we are successful, it may be on terms that are highly dilutive to existing stockholders.
Historically, we have funded our operations by raising capital from external sources and from the Merger. However, we are currently facing significant challenges to our ability to raise capital through the sale of common stock, including the following factors:
in general, it is difficult for development stage companies to raise capital under current market conditions, especially those with early-stage programs like ours;
the perception that we may be unable to continue as a going concern may impede our ability to attract further equity investment; and
our common stock has limited trading volume, which limits the demand for our common stock.
Given these factors, there can be no assurances we will be successful at raising sufficient capital to address our going concern issues. Even if we are successful in raising capital, it may be on terms that are very highly dilutive to existing stockholders. In addition, if we are unable to raise additional capital, we may have to delay, limit, reducecurtail or terminateeliminate one or more of our research and development programs or cease operations.
We have a history of operating losses that are expected to continue for the foreseeable future, and we are unable to predict the extent of future losses, or whether we will generate significant revenues or achieve or sustain profitability.
We are focused on product development and we have not generated any revenues to date. Additionally, we expect to continue to incur operating losses for the foreseeable future. These operating losses have adversely affected and are likely to continue to adversely affect our working capital, total assets and stockholders’ deficit.
Since we are an early-stage company, our prospects must be considered in light of the uncertainties, risks, expenses, and difficulties frequently encountered by companies in their early stages of operations. Specifically, we have generated net losses each year since our inception, including $35.2 million and $28.2 million for the years ended December 31, 2023 and 2022, respectively. We expect to make substantial expenditures and incur increasing operating costs in the future and our accumulated deficit is expected to increase significantly as we expand development and clinical trial activities for our product candidates. Because of the risks and uncertainties associated with product development, we are unable to predict the extent of any future losses, whether we will ever generate significant revenues or if we will ever achieve or sustain profitability.
We believe that our cash on hand will enable us to fund our operations into the third quarter of 2024 based on our current plan. We are dependent on obtaining, and are continuing to pursue, necessary funding from outside sources, including obtaining additional funding from the issuance of securities in order to continue our operations. Without adequate funding, we may not be able to meet our financial obligations.
We have not demonstrated an ability to perform the functions necessary for the successful commercialization of any products. The successful commercialization of any of our products will require us to perform a variety of functions, including:
continuing to undertake preclinical and clinical development;
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engaging in the development of product candidate formulations and manufacturing processes;
interacting with the applicable regulatory authorities and pursuing other required steps for regulatory approval;
engaging with payors and other pricing and reimbursement authorities;
submitting marketing applications to and receiving approval from the applicable regulatory authorities; and
manufacturing the applicable products and product candidates in accordance with regulatory requirements and, if ultimately approved, conducting sales and marketing activities in accordance with health care, FDA and similar foreign regulatory authority laws and regulations.
We have never generated revenue from product sales and may never become profitable.
We have no products approved for commercialization and have never generated any product revenue. Our ability to generate product sales and achieve profitability depends on our ability, alone or with collaborative partners, to successfully complete the development of, and obtain the regulatory approvals necessary to commercialize our current and future product candidates. We do not anticipate generating product sales for the next several years, if ever.
Our product candidates will require additional clinical, manufacturing, and non-clinical development, regulatory approval, commercial manufacturing arrangements, establishment of a commercial organization, significant marketing efforts, and further investment before they generate any product sales. We cannot guarantee that we will meet our timelines for our development programs, which may be delayed or grant rightsmay not be completed for a number of reasons. Our ability to developgenerate future revenues from product sales depends heavily on our, or our collaborators’, ability to successfully:
complete research and marketobtain favorable results from nonclinical and clinical development of our current and future product candidates, including addressing any clinical holds that may be placed on our development activities in the future by regulatory authorities;
seek and obtain regulatory and marketing approvals for any of our product candidates evenfor which we complete clinical trials, as well as their manufacturing facilities;
launch and commercialize any of our product candidates for which we obtain regulatory and marketing approval by establishing a sales force, marketing, and distribution infrastructure or, alternatively, collaborating with a commercialization partner;
qualify for coverage and establish adequate reimbursement by government and third-party payors for any of our product candidates for which we obtain regulatory and marketing approval;
develop, maintain, and enhance a sustainable, scalable, reproducible, and transferable manufacturing process for the product candidates we may develop;
establish and maintain supply and manufacturing capabilities or capacities internally or with third parties that can provide adequate, in both amount and quality, products, and services to support clinical development and the market demand for any of our product candidates for which we obtain regulatory and marketing approval;
obtain market acceptance of current or any future product candidates as viable treatment options and effectively compete with other therapies to establish market share;
maintain a continued acceptable safety and efficacy profile of our product candidates following launch;
address competing technological and market developments;
implement internal systems and infrastructure, as needed;
negotiate favorable terms in any collaboration, licensing, or other arrangements into which we may enter and perform its obligations in such collaborations;
maintain, protect, enforce, defend, and expand our portfolio of intellectual property rights, including patents, trade secrets, and know-how;
avoid and defend against third-party interference, infringement, and other intellectual property claims; and
attract, hire, and retain qualified personnel.
Even if one or more of our current and future product candidates are approved for commercial sale, we anticipate incurring significant costs associated with commercializing any approved product candidate. Our expenses could increase beyond our expectations if we would otherwise preferare required by the FDA or other regulatory authorities to developperform clinical and market such product candidates ourselves.
Risks Relatingother studies in addition to the Development and Regulatory Approval of Our Product Candidates
COVID-19 could adversely impact our business, including ourthose that we currently anticipate. If we are required to conduct additional clinical trials and financial condition.
We have been and continue to be subject to risks related to public health crises such as the global pandemic associated with COVID-19. As COVID-19 continues to persist around the globe, we may continue to experience disruptions that could severely impact our business and clinical trials, including:
delays or difficulties in enrolling patients in our clinical trials, including our ANG-3070 Phase 2 study in PPKD with clinical sites in Eastern Europe, namely Georgia, Lithuania and Bulgaria;
delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff;
diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials;
interruption of key clinical trial activities, such as clinical trial site monitoring, due to limitations on travel imposed or recommended by federal or state governments, employers and others or interruption of clinical trial subject visits and study procedures, the occurrence of which could affect the integrity of clinical trial data;
risk that participants enrolled in our clinical trials will acquire COVID-19 while the clinical trial is ongoing, which could impact the results of the clinical trial, including by increasing the number of observed adverse events;
limitations in employee resources that would otherwise be focused on the conduct of our clinical trials, including because of sickness of employees or their families or the desire of employees to avoid contact with large groups of people;
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delays in receiving authorizations from local regulatory authorities to initiate our planned clinical trials;
delays in clinical sites receiving the supplies and materials needed to conduct our clinical trials;
interruption in global shipping that may affect the transport of clinical trial materials, such as investigational drug product used in our clinical trials;
changes in local regulations as part of a response to the COVID-19 pandemic which may require us to change the ways in which our clinical trials are conducted, which may result in unexpected costs, or to discontinue the clinical trials altogether;
interruptions or delays in preclinical studies due to restricted or limited operations at our research and development laboratory facilities;
delays in necessary interactions with local regulators, ethics committees and other important agencies and contractors due to limitations in employee resources or forced furlough of government employees; and refusal of the FDA to accept data from clinical trials in affected geographies outside the United States.
We are continuing to evaluate the impact of the COVID-19 restrictions on our expected pace of enrollment, as such impacts could delay the timing of topline results in our ongoing clinical trials.
The global pandemic of COVID-19 continues to evolve. The extent to which COVID-19 may impact our business, including our clinical trials, and financial condition will depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the geographic spread of the disease and its variants, business closures or business disruptions and the effectiveness of actions taken in the United States and other countries to contain and treat the disease.

Product development and regulatory approval involve a lengthy and expensive process with uncertain outcomes. We cannot be certain ANG-3070 or any of our other product candidates will receive or maintain regulatory approval and, without regulatory approval, we and our collaborators will not be able to market our product candidates.
We currently have no products approved for sale, and we cannot guarantee we will ever have approved products that we or our collaborators can market and sell. The development of a product candidate and issues relating to its approval and marketing are subject to extensive regulation by regulatory authorities, including the FDA in the United States and other regulatory authorities in other foreign countries, with regulations differing from country to country. We are not permitted to market our product candidates in the United States or elsewhere until we receive regulatory approval and/or marketing authorization, such as approval of an NDA from the FDA. We have not submitted any marketing applications for any of our product candidates.
New drug marketing applications must include extensive preclinical and clinical data and supporting information to establish the product candidate's safety and effectiveness for each desired indication. Such marketing applications must also include significant information regarding the chemistry, manufacturing, and controls for the product. Obtaining approvaltesting of our product candidates will be a lengthy, expensive, and uncertain process, and we may not be successful. Specifically, the review processes of the FDA and foreign regulatory authorities can take years to complete, and approval is never guaranteed. Even if a product is approved, the FDA or foreign regulatory authorities may limit the indications for which the product may be marketed, require extensive warnings on the product labeling or require expensive and time-consuming additional clinical trials or reporting as conditions of approval. The FDA or foreign regulatory authorities also may not approve our product candidates with the labeling that we believe is necessary or desirable for the successful commercialization of such product candidates. Obtaining regulatory approval for marketing of a product candidate in one country does not ensuredevelop beyond those that we will be ablecurrently expect, if we are unable to obtain regulatory approval in any other country.
The FDA or any foreign regulatory authorities can delay, limit or deny approval of our product candidates for many reasons, including:
our inability to demonstrate to the satisfaction of the FDA or the applicable foreign regulatory authority that any of our product candidates are safe and effective for the requested indication;
the FDA's or the applicable foreign regulatory authority's disagreement with our trial protocols or the interpretation of data from preclinical studies or clinical trials;
our inability to demonstrate that the clinical and other benefits of any of our product candidates outweigh any safety or other perceived risks;
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the FDA's or the applicable foreign regulatory authority's requirement for additional preclinical studies or clinical trials;
the FDA's or the applicable foreign regulatory authority's non-approval of the formulation, labeling or specifications of any of our product candidates;
the FDA's or the applicable foreign regulatory authority's failure to approve our manufacturing processes and facilities or the facilities of third-party manufacturers upon which we rely; or
the potential for approval policies or regulations of the FDA or the applicable foreign regulatory authorities to significantly change in a manner rendering our clinical data insufficient for approval.
We cannot predict whether our ongoing or futuresuccessfully complete clinical trials of our product candidates will be successful, or whether regulators will agree with our conclusions regardingother testing, if the preclinical studies and clinicalresults of these trials we have conducted to date or that we conduct in the future. Accordingly,tests are not positive or are only modestly positive, or if there are safety concerns, we may never receivebe delayed in obtaining marketing approval of ANG-3070 or any of our other product candidates, or be authorized to market and sellfor our product candidates, to customers. Ifnot obtain marketing approval at all, or obtain more limited approvals. Even if we are unableable to generate revenues from the sale of any approved product candidates, we may not become profitable and may need to obtain approval from regulatory authorities for ANG-3070 or any of our other product candidates,additional funding to continue operations.
Even if we do achieve profitability, we may not be able to generate sufficient revenuesustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable or to continuewould decrease our operations.

Delays or difficulties in the commencement, enrollment and completion of clinical trials could result in increased costs to us and delay or limit our ability to obtain regulatory approval for ANG-3070 and our other product candidates.
Delays in the commencement, enrollment, and completion of clinical trials could increase our product development costs or limit the regulatory approval of our product candidates. We are currently enrolling patients in our Phase 2 clinical trial of ANG-3070 for PPKD. Delays in any of our clinical trials may increase the amount of additional funding we will require to complete these trials. The commencement, enrollment, and completion of clinical trials can be delayed, challenged or suspended for a variety of reasons, including but not limited to:
severity of the disease under investigation;
inability to obtain sufficient funds required for a clinical trial;
inability to obtain Institutional Review Board (IRB) approval at participating institutions;
our ability to effectively manage the clinical research organizations (CROs) we have engaged to conduct of our clinical trials;
the extent to which COVID-19 may impact our clinical trials and our or our CROs' ability to monitor such trials;
the extent to which the Russian invasion of Ukraine may impact our clinical trials and our or our CROs' ability to monitor such trials;
availability and efficacy of approved medications or competing product candidates in development for the disease under investigation;
the patient eligibility criteria defined in the protocol;
the ability to attract and retain patients and the general willingness of patients to enroll, consent and complete participation in the trial;
the extent to which there is competition for patients to enroll in clinical trials;
the size of the patient population required for analysis of the trial's primary endpoint or endpoints;
clinical holds, other regulatory objections to commencing or continuing a clinical trial, or the inability to obtain regulatory approval to commence a clinical trial in countries requiring such approvals;
discussions with the FDA or foreign regulatory authorities regarding the scope or design of our clinical trials;
severe or unexpected drug-related adverse effects experienced by patients; and
inability to timely manufacture sufficient quantities of the product candidate and other clinical supplies required for a clinical trial.
Changes in regulatory requirements and related guidance related to regulatory approval may also occur and we may need to amend clinical trial protocols to reflect these changes. Amendments may require us to resubmit clinical trial protocols to IRBs for re-examination, which may impact the costs, timing or successful completion of our clinical trials.
Furthermore, if we are required to conduct additional clinical trials or other preclinical studies of our product candidates beyond those contemplated, our ability to obtain or maintain regulatory approval of these product candidates and generate revenue from their sales would be similarly harmed.
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Clinical failure can occur at any stage of clinical development, and the results of earlier clinical trials are not necessarily predictive of future results.
Clinical failure can occur at any stage of our clinical development. For example, in the fourth quarter of 2021, we disclosed the results of the ANG-3777 Phase 3 clinical trial for delayed graft function (DGF) and AKI associated with cardiac surgery involving cardiopulmonary bypass (CSA-AKI), neither of which met their primary endpoints despite the existence of encouraging pre-clinical and clinical data for ANG-3777 established prior to initiating such studies. Clinical trials may produce negative or inconclusive results, and we or our collaborators may decide, or regulators may require us, to conduct additional clinical trials or preclinical studies. In addition, data obtained from trials and studies are susceptible to various interpretations, and regulators may not interpret our data as favorably as we do, which may delay, limit or prevent regulatory approval. Success in preclinical studies and early clinical trials does not ensure subsequent clinical trials will generate the same or similar results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate. A number of companies in the pharmaceutical industry, including those with greater resources and experience than us, have suffered significant setbacks in Phase 3 registration trials, even after seeing promising results in earlier clinical trials.
In addition, the design of a clinical trial can determine whether its results will support approval of a product, and flaws in the design of a clinical trial may not become apparent until the clinical trial is well advanced. We have limited experience in designing clinical trials as we have never previously completed a Phase 3 registration trial with results sufficient to obtain regulatory approval or submitted an NDA to the FDA or a marketing application to any foreign regulatory authority, and we may be unable to design and execute a clinical trial to support regulatory approval. Further, clinical trials of potential products often reveal it is not practical or feasible to continue development efforts.
Furthermore, our ability to show statistical significance in our clinical trials may be affected by factors beyond our control. This could result in the need for additional clinical trials prior to submission of an NDA to the FDA or other marketing applications to foreign regulatory authorities.
There can also be significant variability in safety and/or efficacy results between different trials of the same product candidate due to numerous factors, including changes in trial protocols, differences in composition of the patient populations, adherence to the dosing regimen and other trial protocols, differences in drug lot manufacturing, and the rate of dropout among clinical trial participants. We do not know whether any preclinical or clinical trials we or any of our existing or future collaborators may conduct will demonstrate consistent or adequate efficacy and safety to obtain regulatory approval to market our product candidates.
If ANG-3070 or our other product candidates are the subject of clinical trial failures or are found to be unsafe or lack efficacy, we will not be able to obtain regulatory approval for them and our business would be harmed.

Our clinical trials could be disrupted by the uncertainty of war due to the aggressive actions taken by Russia which, if this occurs, could delay our ability to complete our clinical trials.
We are currently in the process of advancing ANG-3070 through a Phase 2 clinical trial in 100 patients with Primary Proteinuria Kidney Diseases (PPKD), specifically FSGS and IgAN patients, including trial sites in Georgia, Bulgaria and Lithuania. In late February 2022, Russia initiated significant military action against Ukraine, and given the proximity of Georgia, Bulgaria and Lithuania to Russia there may be significant uncertainty and unrest in these countries which could impair or delay the progress of our clinical trials in those countries. Further, in response to the Russian invasion of Ukraine, the U.S. and certain other countries imposed significant sanctions and trade actions against Russia, and the U.S. and certain other countries could impose further sanctions, trade restrictions and other retaliatory actions should the conflict continue or worsen. It is not possible to predict the broader consequences of the conflict, including related geopolitical tensions, and the measures and retaliatory actions taken by the U.S. and other countries in respect thereof, as well as any counter measures or retaliatory actions by Russia in response, is likely to cause regional instability, geopolitical shiftsvalue and could materially adversely affect global trade, currency exchange rates, regional economies and the global economy. In particular, while it is difficult to anticipate the impact of any of the foregoing on our clinical trials or our business, the conflict and actions taken in response to the conflict could increase our costs, disrupt our supply chain, impair the progress of our clinical trials, impair our ability to raise
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additional capital, when needed on acceptable terms, if at all, or otherwise adversely affectmaintain our business, financial condition and results of operations.

Even if we successfully complete ongoing and planned clinical trials of one or more of our product candidates, the product candidates may fail for other reasons.
Even if we successfully complete the clinical trials for one or more of our product candidates, such product candidates may fail for other reasons, including the possibility the product candidates will:
fail to receive the regulatory approvals required to market them as drugs;
be subject to proprietary rights held by others requiring the negotiation of a license agreement prior to marketing;
be difficult or expensive to manufacture on a commercial scale;
have adverse side effects that make their use less desirable;
not achieve reimbursement or sales levels sufficient for continued marketing; or
fail to compete with product candidates or other treatments commercialized by our competitors.
If we are unable to receive and maintain the required regulatory approvals, secure our intellectual property rights, maintain an acceptable safety profile or fail to compete with our competitors' products, our business, financial condition, and results of operations could be materially and adversely affected.

Our product candidates may have undesirable side effects which may delay or halt clinical development or prevent marketing approval or, if approval is received, require them to be taken off the market, require them to include safety warnings, or otherwise limit their sales.
The results of our clinical trials of our product candidates may show that such product candidates led to patient safety concerns or undesirable or unacceptable side effects, creating risk to the patient which is deemed to outweigh the potential benefits of treatment to that patient. Unforeseen side effects from any of our product candidates could arise either during clinical development or, if approved, after the approved product has been marketed. Any such event could interrupt, delay or halt such clinical trials, resulting in the denial of regulatory approval by the FDA and other regulatory authorities or result in restrictive label warnings, if approved. In light of widely publicized events concerning the safety risk of certain drug products, regulatory authorities, members of Congress, the Government Accounting Office, medical professionals and the general public have raised concerns about potential drug safety issues. These events have resulted in the withdrawal of drug products, revisions to drug labeling that further limit use of the drug products and establishment of risk management programs that may, for instance, restrict distribution of drug products. The increased attention to drug safety issues may result in a more cautious approach by the FDA to clinical trials. Data from clinical trials may receive greater scrutiny with respect to safety, which may make the FDA or other regulatory authorities more likely to terminate clinical trials before completion, or require longer or additional clinical trials that may result in substantial additional expense and a delay or failure in obtaining approval or approval for a more limited indication than originally sought.
ANG-3070 is a tyrosine kinase inhibitor (TKI). TKIs are widely used across a range of indications. Depending on their specific targets, TKIs have been associated with several near and long-term side effects. They have been most extensively used in cancer where cardiopulmonary toxicity, myelosuppression, and gastrointestinal toxicity have been key side effects in addition to several others. TKIs have also been studied in fibrosis, with nintedanib being approved for IPF. Nintedanib has been associated with several side effects including severe liver injuries, arterial thromboembolic events and gastrointestinal disorders including diarrhea, nausea and vomiting, and risk of bleeding. Pirfenidone, with an unknown mechanism of action, has also been approved in IPF and has been associated with elevated liver enzymes, diarrhea, nausea vomiting, photosensitivity and rash.
While we believe the preliminary safety and pharmacokinetic data from our Phase 1 healthy-volunteer study in Australia support the conduct of our ongoing Phase 2 clinical trial in PPKD and additional clinical trials, there can be no assurance similar or unforeseen side effects will not occur during such clinical trial. The range and potential severity of possible side effects from systemic therapies is significant.
If any of our product candidates receives marketing approval and we or others later identify undesirable or unacceptable side effects caused by such products:
regulatory authorities may require the addition of labeling statements or specific warnings, including "Black Box" warnings if the FDA views the possible side effects as very severe;
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we may be required to change instructions regarding the way the product is administered, conduct additional clinical trials, or change the labeling of the product;
we may be subject to limitations on how we may promote the product;
sales of the product may decrease significantly;
regulatory authorities may require us to take our approved product off the market;
we may be subject to litigation or product liability claims; and
our reputation may suffer.
Any of these events could prevent us or any potential future collaborators from achieving or maintaining market acceptance of the affected product or could substantially increase commercialization costs and expenses, which, in turn, could delay or prevent us from generating significant revenues from the sale of our products.

Clinical trials of our product candidates may not uncover all possible adverse effects patients may experience or be indicative of the effect of our product candidates post approval in the general population.
Clinical trials are conducted in representative samples of the potential patient population, which may have significant variability. By design, clinical trials are based on a limited number of subjects and are of limited duration of exposure to the product, to determine whether the product candidate demonstrates the substantial evidence of efficacy and safety necessary to obtain regulatory approval. As with the results of any statistical sampling, we cannot be sure that any evidence of efficacy will be repeated in the general population or all side effects of our product candidates may be uncovered. It may be the case that only with a significantly larger number of patients exposed to the product candidate for a longer duration may a more complete safety and efficacy profile be identified Further, even larger clinical trials may not identify rare serious adverse events, and the duration of such studies may not be sufficient to identify when those events may occur particularly for adverse events or safety risks that could occur over time, such as the development and diagnosis of cancer. Other products have been approved by the regulatory authorities for which safety concerns have been uncovered following approval. Such safety concerns have led to labeling changes, restrictions on distribution through use of a REMS, or withdrawal of products from the market, and any of our product candidates may be subject to similar risks.
Patients treated with our products, if approved, may experience previously unreported adverse reactions, and it is possible that the FDA or other regulatory authorities may ask for additional safety data as a condition of, or in connection with, our efforts to obtain approval of our product candidates. If safety problems occur or are identified after our products, if any, reach the market, we may make the decision or be required by regulatory authorities to amend the labeling of our products, recall our products, or even withdraw approval for our products.

Due to the significant resources required for the development and commercialization of our product candidates, we must prioritize development of certain product candidates and/or certain disease indications. We may expend our limited resources on product candidates or indications that do not yield a successful product and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.
We plan to develop a pipeline of product candidates to treat potentially life-threatening acute organ injuries and fibrotic diseases. However, due to the significant resources required for the development of our product candidates, we must focus on specific indications and decide which product candidates to pursue and the amount of resources to allocate to each. For instance, in 2022, we plan to identify a lead candidate in one or more of our pre-clinical programs, but not in all such programs.Our primary focus is on advancing ANG-3070 in PPKD through our ongoing Phase 2 dose-finding study in that population and filing an IND to support the clinical development of ANG-3070 in IPF.
Our decisions concerning the allocation of research, development, collaboration, management and financial resources toward particular product candidates or therapeutic areas may not lead to the development of any viable commercial product and may divert resources away from better opportunities. Similarly, our potential decisions to delay, terminate or collaborate with third parties in respect of certain programs may subsequently also prove to be suboptimal and could cause us to miss valuable opportunities. If we make incorrect determinations regarding the viability or market potential of any of our programs or product candidates or misread trends in the biopharmaceutical industry, our business, financial condition and results of operations could be materially adversely affected. As a result, we may fail to capitalize on viable commercial products or profitable market opportunities, be required to
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forego or delay pursuit of opportunities with other product candidates or other diseases that may later prove to have greater commercial potential than those we choose to pursue, or relinquish valuable rights to such product candidates through collaboration, licensing or other royalty arrangements in cases in which it would have been advantageous for us to invest additional resources to retain development and commercialization rights.
Our business operations and current and future relationships with investigators, healthcare professionals, consultants, third-party payors, patient organizations and customers will be subject to applicable healthcare regulatory laws, which could expose us to penalties.
Our business operations and current and future arrangements with investigators, healthcare professionals, consultants, third-party payors, patient organizations and customers, may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations. These laws may constrain the business or financial arrangements and relationships through which we conduct our operations, including how we research, market, sell and distribute our product candidates, if approved. Such laws include: the U.S. federal Anti-Kickback Statute; U.S. federal civil and criminal false claims laws, including the civil False Claims Act; the federal fraud provision of the U.S. federal Health Insurance Portability and Accountability Act of 1996 (HIPAA); HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH; the FDCA; the U.S. Physician Payments Sunshine Act; federal consumer protection and unfair competition laws; analogous U.S. state laws and regulations, including state anti-kickback and false claims laws; and similar healthcare laws and regulations in the EU and other jurisdictions, including reporting requirements detailing interactions with and payments to healthcare providers.
Ensuring that our current internal operations and future business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices, including our relationships with physicians and other healthcare providers, some of whom are compensated in the form of stock options for consulting services provided, may not comply with current or future statutes, regulations, agency guidance or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to significant penalties, including civil, criminal and administrative penalties, damages, fines, exclusion from government-funded healthcare programs, such as Medicare and Medicaid or similar programs in other countries or jurisdictions, integrity oversight and reporting obligations to resolve allegations of non-compliance, disgorgement, individual imprisonment, contractual damages, reputational harm, diminished profits and the curtailment or restructuring of our operations. If any of the physicians or other providers or entities with whom we expect to do business are found to not be in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs and imprisonment, which could affect our ability to operate our business. Further, defending against any such actions can be costly, time-consuming and may require significant personnel resources. Therefore, even if we are successful in defending against any such actions that may be brought against us, our business and our ability to sell our products may be materially harmed.

Recently enacted and future legislation may increase the difficulty and cost for us to obtain marketing approval for and commercialize our product candidates and affect the prices we may obtain.
In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability to profitably sell any product candidates for which we obtain marketing approval.
In the United States, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Affordability Reconciliation Act (Affordable Care Act), was intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.
Since its enactment, there have been judicial, executive branch and congressional challenges to certain aspects of the Affordable Care Act, and we expect there will be additional challenges and amendments to the Affordable Care Act in the future. For example, legislation informally titled the Tax Cuts and Jobs Acts (TCJA) was enacted, which, among other things, removed penalties for not complying with the individual mandate to carry health insurance. On June 17, 2021 the U.S. Supreme Court dismissed a challenge on procedural grounds that argued the Affordable Care Act is unconstitutional in its entirety because the “individual mandate” was repealed by
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Congress. Thus, the Affordable Care Act will remain in effect in its current form. It is possible that the Affordable Care Act will be subject to judicial or congressional challenges in the future. It is unclear how such challenges or the health reform measures of the Biden administration will affect the Affordable Care Act or our business.
In addition, other legislative changes have been proposed and adopted since the Affordable Care Act was enacted. In August 2011, the Budget Control Act of 2011, among other things, included aggregate reductions of Medicare payments to providers of 2% per fiscal year, which went into effect on April 1, 2013 and, due to subsequent legislative amendments, will remain in effect through 2031, with the exception of a temporary suspension from May 1, 2020 through March 31, 2022, unless additional congressional action is taken. Under current legislation, the actual reduction in Medicare payments will vary from 1% in 2022 to up to 3% in the final fiscal year of this sequester. In addition, on January 2, 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, which, among other things, reduced Medicare payments to several providers, including hospitals, and an increase in the statute of limitations period for the government to recover overpayments to providers from three to five years. These new laws may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain.
We expect that other healthcare reform measures that may be adopted in the future may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and in additional downward pressure on the price that we receive for any approved product. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability or commercialize our product candidates, if approved.
Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products. In July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs. In response to Biden’s executive order, on September 9, 2021, HHS released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue to advance these principles. No legislation or administrative actions have been finalized to implement these principles. In addition, Congress is considering drug pricing as part of other reform initiatives.Individual states in the United States have become increasingly aggressive in implementing regulations designed to contain pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures. Legally mandated price controls on payment amounts by third-party payors or other restrictions could harm our business, results of operations, financial condition and prospects. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. This could reduce the ultimate demand for our product candidates, if approved, or put pressure on our product pricing, which could negatively affect our business, results of operations, financial condition and prospects.
Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products. We cannot be sure whether additional legislative changes will be enacted, or whether the FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals of our product candidates, if any, may be. In addition, increased scrutiny by Congress of the FDA's approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post-marketing testing and other requirements.

We rely on single-source third party contract manufacturing organizations to manufacture and supply our product candidates, and if the FDA or foreign regulatory authorities do not approve these manufacturing facilities or if these organizations fail to perform, our ability to conduct clinical trials and obtain regulatory approval our product candidates may be harmed.
We do not own facilities for clinical and commercial manufacturing of our product candidates, including ANG-3070, and we rely upon third-party contract manufacturing organizations to manufacture and supply product candidates for our clinical trials and we will rely in such manufacturers to meet commercial demand. Currently, we rely on and have agreements with a single third-party contract manufacturer to supply the drug substance for ANG-3070 and to manufacture all clinical trial supplies of ANG-3070.
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Additionally, the facilities at which ANG-3070 or any of our other product candidates are manufactured must be the subject of a satisfactory inspection before the FDA or the regulators in other jurisdictions approve the product candidate manufactured at that facility. We are completely dependent our third-party vendors for compliance with the current Good Manufacturing Practice requirements (cGMPs). requirements of United States and non-United States regulators for the manufacture of our active ingredients, drug products, and finished products. If our manufacturers cannot successfully manufacture material conforming to our specifications and cGMPs of any applicable governmental agency, our product candidates will not be approved or, if already approved, may be subject to recalls or demands by regulatory agencies to stop selling the product until manufacturing issues are resolved.
Reliance on third-party manufacturers entails risks to which we would not be subject if we manufactured the product candidates, including:
the possibility we are unable to enter into a manufacturing agreement with a third party to manufacture our product candidates;
the possible breach of the manufacturing agreements by the third parties because of factors beyond our control; and
the possibility of termination or nonrenewal of the agreements by the third parties before we are able to arrange for a qualified replacement third-party manufacturer.
Any of these factors could delay the development or approval of our product candidates, cause us to incur higher costs or prevent us from developing our product candidates successfully. Furthermore, if the supply chain for our clinical trial materials is interrupted or if any of our contract manufacturers fail to deliver the required clinical trial supplies on a timely basis and at commercially reasonable prices and we are unable to find one or more replacement manufacturers capable of production at a substantially equivalent cost, in substantially equivalent volumes and quality and on a timely basis, we may be unable to supply our clinical trial programs with clinical trial materials which could delay our programs and increase our costs. For instance, we are conducting our ongoing Phase 2 of ANG-3070 in certain countries in Eastern Europe, namely Georgia, Bulgaria, and Lithuania. If our supply chain in the region is interrupted for any reason, including the current war in Ukraine, the dosing of patients in our Phase 2 clinical trial could be slowed, delayed or stopped. Further, such challenges could be compounded by the COVID-19 pandemic.

Changes in structure of or funding for the FDA and other government agencies could hinder their ability to hire and retain key leadership and other personnel, or otherwise prevent new products and services from being developed in a timely manner, which could negatively impact our business.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel, the maintenance of regulatory review timelines, and statutory, regulatory, and policy changes. Average review times at the agency have fluctuated in recent years as a result. In addition, government funding of other government agencies that fund research and development activities is subjectefforts, expand our business or continue our operations. A decline in our value also could cause our stockholders to the political process, which is inherently fluid and unpredictable. The lacklose all or part of appropriate funding or appropriate resource for the FDA, could have material adverse effect on our ability to develop ANG-3070 and our product candidates.

their investment.
We have and may continue to conduct future clinical trials outside of the United States. The FDA and other regulatory authorities may not accept data from such trials, in which case our development plans will be delayed, which could materially harm our business.
We are enrolling or plan to enroll patients in our Phase 2 clinical trial of ANG-3070 for PPKD in Georgia, Australia, Lithuania, Bulgaria, Spain, Italy and potentially other jurisdictions under separate clinical trial applications in such jurisdictions. Although the FDA may accept data from clinical trials conducted outside the United States, acceptance of this data is subject to certain conditions imposed by the FDA. For example, the FDA requires the clinical trial to have been conducted in accordance with GCPs, and the FDA must be able to validate the data from the clinical trial through an onsite inspection if it deems such inspection necessary. In addition, when clinical trials are conducted only at sites outside of the United States, such trials may not be subject to IND review, meaning the FDA may not provide advance comment on the clinical protocols for the trials, and therefore there is an additional potential risk that the FDA could determine that the study design or protocol for a non-U.S. clinical trial was inadequate, which would likely require additional clinical trials in order to seek FDA approval. If the FDA does not
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accept data from our clinical trials of ANG-3070 and any future product candidates conducted outside the United States, it would likely result in the need for additional clinical trials, which would be costly and time consuming and delay or permanently halt our development of ANG-3070 and any future product candidates.
Conducting clinical trials outside the United States also exposes us to additional risks, including risks associated with:
additional foreign regulatory requirements;
foreign exchange fluctuations;
patient monitoring and compliance;
compliance with foreign manufacturing, customs, shipment and storage requirements;
cultural differences in medical practice and clinical research;
diminished protection of intellectual property in some countries, and
operational risks resulting from war and conflict certain countries or in proximity to the countries in which we are conducting our clinical trials.

If manufacturers obtain approval for generic versions of our products or product candidates, our business will be materially harmed.
In our industry, much of an innovative product's commercial value is realized while it has patent protections and market exclusivity. When market exclusivity expires generic versions of the product can be approved and marketed, and there can be substantial decline in the innovative product's sales.
Market exclusivity for our products is based upon patent rights and certain regulatory forms of exclusivity. If we are unable to secure or maintain our exclusivities, we may face generic competition that could materially impede our ability to effectively commercialize our products, including be reducing the price we can charge and reducing our market share.ANG-3070 and our other product candidates are protected by a number of granted and pending patent applications, and may be entitled to certain regulatory exclusivities if approved.
In some countries, patent protections for our products may not exist because certain countries did not historically offer the right to obtain specific types of patents or we did not file patents in those markets. Also, the patent environment is unpredictable and the validity and enforceability of patents cannot be predicted with certainty.
Specifically, with regard to the potential for generic entry in the United States, under the U.S. Food, Drug and Cosmetic Act (FDCA) the FDA can approve an Abbreviated New Drug Application (ANDA) for a generic version of an approved branded drug without the ANDA applicant undertaking the clinical testing necessary to obtain approval to market a new drug. Generally, in place of such clinical studies, an ANDA applicant needs only to submit data demonstrating that its product has the same active ingredient(s), strength, dosage form, route of administration and that it is bioequivalent to the approved product.
The FDCA requires that an ANDA applicant certify either that its generic product does not infringe any of the patents listed by the owner of the branded drug in the Orange Book or that those patents are not enforceable. This process is known as a paragraph IV certification. Upon notice of a paragraph IV certification, a patent owner or NDA holder has 45 days to bring a patent infringement suit in federal district court against the company seeking ANDA approval of a product covered by one of the owner's patents. If this type of suit is commenced, the FDCA provides a 30-month stay on the FDA's approval of the competitor's application. If the litigation is resolved in favor of the ANDA applicant or the challenged patent expires during the 30-month stay period, the stay is lifted and the FDA may thereafter approve the application based on the standards for approval of ANDAs. Once an ANDA is approved by the FDA, the generic manufacturer may market and sell the generic form of the branded drug in competition with the branded medicine.
The ANDA process can result in generic competition if the patents at issue are not upheld or if the generic competitor is found not to infringe the owner's patents. If this were to occur with respect to any of our product candidates after approval, our business could be materially harmed.

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Risks Relating to Collaborations and Commercialization of Our Product Candidates
If we are able to develop and obtain regulatory approval for any of our product candidates, our business will be materially harmed if we are unable to successfully commercialize such approved products.
Even if we receive regulatory approval of any product candidate, including ANG-3070, it is uncertain whether we will be able to successfully commercialize such product. Our marketing of any approved product will be limited to the product’s approved use and potentially subject to other limitations as set forth in its approved prescribing information and package insert. Accordingly, we cannot ensure any of our future approved products will be successfully developed, approved or commercialized. If we are unable to successfully commercialize our future approved products, we may not be able to generate sufficient revenue to operate our business. In particular, the future commercial success of any approved product is subject to a number of risks, including the following:
the emergence of unknown side effects causing an approved drug to be taken off the market;
the receipt of market acceptance by physicians, hospitals, payers and patients;
our ability to obtain meaningful pricing and reimbursement for any approved product, and
our ability to obtain, maintain or enforce our patents and other intellectual property rights related to our approved products.
Our existing collaborations as well as additional collaboration arrangements we may enter into in the future may not be successful, which could adversely affect our ability to develop and commercialize our product candidates.
We have licensed certain rights with respect to ANG-3777 to Vifor Pharma, and in the future we may seek additional collaboration arrangements for the commercialization, or potentially for the development, of certain of our product candidates depending on the merits of retaining development and/or commercialization rights for ourselves as compared to entering into collaboration arrangements.
The success of our existing and any future collaboration arrangements, will depend heavily our ability with our collaborators to develop and obtain approval of the any licensed product or product candidate and on the efforts and activities of our collaborators. For instance, in November 2020, we entered into a license agreement (the Vifor License) with Vifor International, Ltd. (Vifor Pharma), granting Vifor Pharma global rights (excluding Greater China) to develop, manufacture and commercialize ANG-3777 in all therapeutic, prophylactic and diagnostic uses for renal indications and congestive heart failure. Pursuant to the Vifor License, we are eligible to receive certain clinical, post-approval, or sales milestone payments, and/or royalties, based upon the clinical development plan for ANG-3777 set forth in Vifor License. However, we do not expect to receive any such payments as we do not intend to continue to pursue the clinical development plan for ANG-3777 set forth in the Vifor License, which had included a Phase 3 study for CSA-AKI and a Phase 4 confirmatory study in DGF, for ANG-3777 based upon clinical trial results for ANG-3777 disclosed in the fourth quarter of 2021.
Further, our dependence on collaborative arrangements subjects us to a number of risks, including the risk we may never receive substantial economic benefit from the arrangements, we may not be able to control the amount and timing of resources our collaborators may devote to the product candidates; our collaborators may experience financial difficulties; business combinations or significant changes in a collaborator's business strategy may also adversely affect a collaborator's willingness or ability to complete its obligations under any arrangement; and collaboration arrangements may be terminated or allowed to expire, which would delay the development and may increase the cost of developing our product candidates. Any of these outcomes could harm our business.
Additionally, to the extent we decide to enter into additional collaboration agreements in the future, we may face significant competition in seeking appropriate collaborators. Moreover, collaboration arrangements are complex and time-consuming to negotiate, document, implement and maintain. We may not be successful in our efforts to prudently manage our existing collaborations or to enter new ones should we chose to do so. The terms of new collaborations or other arrangements that we may establish may not be favorable to us.
If we fail to develop market opportunities for ANG-3070 or any future products are smaller than we believe they are, our potential to generate revenue may be adversely affected, and our business may suffer.
The precise incidence and prevalence for all the conditions we currently or may intend to address with ANG-3070 or any future product candidates are unknown. Our projections of both the number of people who have the diseases we target, as well as the subset of people with these diseases who have the potential to benefit from
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treatment of ANG-3070 or any future product candidates, are based on our beliefs and estimates. These estimates have been derived from a variety of sources, including the scientific literature, surveys of clinics or market research, and may prove to be incorrect. Further, new trials may change the estimated incidence or prevalence of these diseases. The total addressable market across ANG-3070 and any future product candidates will ultimately depend upon, among other things, the diagnosis criteria included in the final label for each of ANG-3070 and any future product candidates approved for sale for these indications, the availability of alternative treatments and the safety, convenience, cost and efficacy of ANG-3070 and any future product candidates relative to such alternative treatments, acceptance by the medical community and patient access, drug pricing and reimbursement. The number of patients in the United States and other major markets and elsewhere may turn out to be lower than expected, patients may not be otherwise amenable to treatment with our products or new patients may become increasingly difficult to identify or gain access to, all of which would adversely affect our results of operations and our business.
Risks Relating to Our Business and Strategy
We face competition from other biotechnology and pharmaceutical companies and our operating results will suffer if we fail to compete effectively.
The biotechnology and pharmaceutical industries are intensely competitive and subject to rapid and significant technological change. We have competitors in the United States, Europe, and other jurisdictions, including major multinational pharmaceutical companies, established biotechnology companies, specialty pharmaceutical and generic drug companies, and universities and other research institutions. Many of our competitors have greater financial and other resources, such as larger research and development staff and more experienced marketing and manufacturing organizations. Large pharmaceutical companies, in particular, have extensive experience in clinical testing, obtaining regulatory approvals, recruiting patients, and manufacturing pharmaceutical products. These companies also have significantly greater research, sales, and marketing capabilities and collaborative arrangements in our target markets with leading companies and research institutions. Established pharmaceutical companies may also invest heavily to accelerate discovery and development of novel compounds or to in-license novel compounds potentially making the product candidates we develop obsolete. As a result of all of these factors, our competitors may succeed in obtaining patent protection and/or FDA approval or discovering, developing, and commercializing drugs for kidney, heart, liver, lung and other diseases we are targeting before we do. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies. In addition, many universities and private and public research institutes may become active in our target disease areas.
With respect to ANG-3070, Tarpeyo® (budesonide) from Calliditas was granted accelerated approved by the FDA for IgAN, one form of PPKD. Phase 3 programs in PPKD include Atrasentan from Chinook Pharmaceuticals (IgAN, FSGS, Alport), Bardoxolone methyl from Reata Pharmaceuticals (Alport), Iptacopan from Novartis (IgAN), Narsoplimab form Omeros (IgAN), Sibeprenlimab from Visterra/Otsuka Pharmaceuticals (IgAN), Sparsenten from Travere Therapeutics (IgAN, FSGS), and DMX-200 from Dimerix (FSGS). There are two approved therapies, pirfenidone (Esbriet®, sold by Roche/Genentech) for IPF and nintedanib (OFEV®, sold by Boehringer-Ingleheim) for IPF and SSc-ILD. Phase 3 clinical programs potentially competitive with ANG-3070 in IPF include ORG-447 from Agomab Therapeutics, PLN-74809 from Pliant Therapeutics, PRM-151 from Roche/Genentech, and Taladegib from Endeavor Biosciences for IPF.
With respect to competition for our ROCK2 inhibitor, netarsudil ophthalmic solution from Aerie Pharmaceuticals, Inc. was first approved by the FDA in 2017 as a topical agent for reducing intraocular pressure in patients with open-angle glaucoma and ocular hypertension. Other competition in clinical development include Kadmon Holdings, Inc.'s belumosudil (KD025), a ROCK2 inhibitor with reduced selectivity against ROCK1, in the clinic for several indications, including chronic graft versus host disease, systemic sclerosis and IPF. CXC007 from Redx Pharma is in Phase 1 trials. We are also aware of other ROCK2 inhibitors in preclinical development.
Regarding competition for our CYP11B2 inhibitor, CIN-107 from CinCor Pharma is in multiple Phase 2 trials for resistant hypertension, uncontrolled hypertension, and primary aldosteronism. PB6440 from PhaseBio is preparing for Phase 1 trials in 2022 in treatment resistant hypertension
We believe our ability to successfully compete will depend on, among other things:
our ability to recruit and enroll patients for our clinical trials;
our ability to design and successfully execute appropriate clinical trials;
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our ability to gain and to maintain positive relationships with regulatory authorities;
the efficacy, safety, and reliability of our product candidates;
the speed at which we develop our product candidates;
our ability to commercialize and market any of our product candidates receiving regulatory approval;
the pricing of our products;
adequate levels of reimbursement by government entities and by private health insurance plans;
our ability to protect intellectual property rights and regulatory exclusivities related to our products;
our ability to manufacture and sell commercial quantities of any approved products to the market; and
acceptance of our product candidates by downstream customers, including physicians, other healthcare providers, pharmacists, and patients.
If our competitors market products more effective, safer, or less expensive than our products or product candidates, or if any, or these products reach the market sooner we may not achieve commercial success. In addition, the biopharmaceutical industry is characterized by rapid technological change. It may be difficult for us to stay abreast of the rapid changes in each area of research and development. If we fail to stay at the forefront of change, we may be unable to compete effectively. Products developed by our competitors may render our product candidates or products obsolete, less competitive or not economical.
We currently depend on single third-party suppliers for the manufacture and supply of drug substance and potential future commercial product supplies for our product candidates, and any performance failure on the part of our supplier could delay the development and potential commercialization of our product candidates.
We cannot be certain that our drug substance supplier will continue to provide us with sufficient quantities of drug substance, or that our manufacturers will be able to produce sufficient quantities of drug product incorporating such drug substance, to satisfy our anticipated specifications and quality requirements, or that such quantities can be obtained at pricing necessary to sustain acceptable pharmaceutical margins for any of our product candidates, if approved. Our current dependence on a single supplier for our drug substance and the challenges we may face in obtaining adequate supply of drug substance involves several risks, including limited control over pricing, availability, quality and delivery schedules, and such risks may be heightened as a result of the COVID-19 pandemic. Any supply interruption in drug substance or drug product could materially harm our ability to complete our development program for such indications. In addition, any supply interruption in drug substance or drug product could materially harm our ability to complete our other development programs or satisfy commercial demand, if approved, until a new source of supply, if any, could be identified and qualified. For instance, we are conducting our ongoing Phase 2 of ANG-3070 in certain countries in Eastern Europe, namely Georgia, Bulgaria, and Lithuania. If our supply chain in the region is interrupted for any reason, including the current war in Ukraine, the dosing of patients in our Phase 2 clinical trial could be slowed, delayed or stopped. We may be unable to find a sufficient alternative supply channel in a reasonable time or on commercially reasonable terms. Any performance failure on the part of our suppliers could delay the development and potential commercialization of our product candidates, including limiting supplies necessary for clinical trials and regulatory approvals, which would have a material adverse effect on our business.
Moreover, our current supplier of drug substance may not have the capacity to manufacture drug substance in the quantities that we believe will be sufficient to meet our future clinical needs or, in the case of any of our wholly-owned product candidates and those for which we retain the right to commercialize, anticipated market demand or to enable us to achieve the economies of scale necessary to reduce the manufacturing cost of applicable drug substance. While we are currently engaged in discussions with a potential second supplier for clinical and commercial drug substance, such negotiations may not lead to a definitive agreement on acceptable terms, or at all, which could have a material adverse effect on our business. With respect to any of our wholly-owned product candidates and those for which we retain the right to commercialize, we expect that we will be able to develop a supply chain with multiple suppliers and significantly decrease our cost of goods within the first several years of commercialization following the receipt of any approvals. However, if our contract manufacturer for drug substance is unable to source, or we are unable to purchase, sufficient quantities of materials necessary for the production of the drug substance for such product candidates, the ability of such product candidates to reach their market potential or to be timely launched, would be delayed or suffer from a shortage in supply, which would impair our ability to generate revenue from sales. If there is a disruption to our contract manufacturers' or suppliers' relevant operations, we could have no other means of producing drug substance until they restore the affected facilities or
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we or they procure alternative manufacturing facilities. Additionally, any damage to or destruction of our contract manufacturers' or suppliers' facilities or equipment may significantly impair our ability to manufacture drug substance for our product candidates on a timely basis.

We depend on third-party contractors for a substantial portion of our operations and may not be able to control their work as effectively as if we performed these functions ourselves. If these third parties do not successfully carry out their contractual duties or meet expected deadlines, we may be unable to obtain regulatory approval for or commercialize our product candidates, if approved.
We outsource substantial portions of our operations to third-party service providers, including the conduct of preclinical studies and clinical trials, collection and analysis of data, and manufacturing. Our agreements with third-party service providers and CROs are on a study-by-study and project-by-project basis. Typically, we may terminate the agreements with notice and are responsible for the supplier's previously incurred costs. In addition, any CRO we retain will be subject to the FDA's and EMA's regulatory requirements and similar standards outside of the United States and Europe,history and we do not have direct control over compliance with these regulations by these providers. Consequently, if these providers do not adhere to applicable governing practices and standards, the development and commercialization of our product candidates could be delayed or stopped, which could severely harm our business and financial condition.
Because we have relied on third parties, our internal capacity to perform these functions is limited to contractual oversight. Outsourcing these functions involves the risk third parties may not perform to our standards, may not produce results in a timely manner or may fail to perform at all. This challenge has been made more difficult by the COVID-19 pandemic and resulting shelter-in-place and stay-at-home restrictions, which are driving greater dependency on electronic monitoring of trial sites. Such monitoring can be less reliable and creates additional exposure to data privacy and cybersecurity issues. Additionally, the facilities at which any of our product candidates are manufactured must be the subject of a satisfactory inspection before the FDA or the regulators in other jurisdictions approve the product candidate manufactured at that facility. We are completely dependent our third-party vendors for compliance with cGMP requirements of United States and non-United States regulators for the manufacture of our finished products. If our manufacturers cannot successfully manufacture material conforming to our specifications and cGMPs of any applicable governmental agency, our product candidates will not be approved or, if already approved, may be subject to recalls or demands by regulatory agencies to stop selling the product until manufacturing issues are resolved. In addition, our third-party service providers and CROs that perform nonclinical studies and clinical trials on our behalf must comply with applicable Good Laboratory Practice (GLP) requirements for animal testing and GCP requirements for clinical trials, where any failure to comply with such requirements could result in the FDA or other regulatory authorities refusing to accept data obtained in violation of such requirements and possibly initiating other enforcement action against us and our contractors.
We and our consultants monitor our third parties for performance and adherence to protocols. We have had to replace clinical sites because of poor enrollment. In addition, the use of third-party service providers requires us to disclose our proprietary information to these parties (including sensitive data such as personal information or clinical data), which could increase the risk this information will be misappropriated or compromised in connection with a security breach, cyber-attack or other security incident. There are a limited number of third-party service providers specializing in or having the expertise required to achieve our business objectives. Identifying, qualifying, and managing performance of third-party service providers can be difficult, time consuming, and cause delays in our development programs. We currently have a relatively small number of employees, which limits the internal resources we have available to identify and monitor third-party service providers. To the extent we are unable to identify, retain, and successfully manage the performance of third-party service providers in the future, our business may be adversely affected, and we may be subject to the imposition of civil or criminal penalties if their conduct of clinical trials violates applicable law.

We will need to maintain a good relationship with our employees to maintain our operations. A deterioration in our relationships with our employees could have an adverse impact on our business.
On January 4, 2022, we announced a reduction in force impacting somewhat less than half of our employees. Our decision to engage in this reduction results from an assessment of our internal resources needs, given the results of the Phase 3 study of ANG-3777 in patients at risk for DGF would likely not support a regulatory approval in that population and the results from a Phase 2 trial in CSA-AKI would not support a Phase 3 trial in the indication. This reduction was a cost-cutting measure across the organization to support our 2022 primary focus on the clinical
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development of its investigational asset ANG-3070, a highly selective, oral tyrosine kinase receptor inhibitor in development as a treatment for fibrotic diseases, particularly in the kidney and lung, as well as advancing preclinical assets to IND-enabling studies. This has caused substantial uncertainty as to job security for the rest of our employees. Maintaining good relationships with our employees and operating effectively and efficiently across our organization are crucial to our operations and our success. If we are unable to successfully maintain such relationships or manage the uncertainty as a result of the reduction in the number of our employees, and the complexity of operations, our business may be adversely affected. See "Item 1. Business—Human Capital Resources."

We may not be able to manage our business effectively if we are unable to attract and retain key personnel and consultants.
We may not be able to attract or retain qualified management, finance, scientific, clinical, and commercial personnel and consultants due to the intense competition for qualified personnel and consultants among biotechnology, pharmaceutical, and other businesses. If we are not able to attract and retain necessary personnel and consultants to accomplish our business objectives, we may experience constraints significantly impeding the achievement of our development objectives, our ability to raise additional capital, and our ability to implement our business strategy.
We are highly dependent upon our senior management, particularly our Chief Executive Officer, Dr. Jay Venkatesan, as well as on the development, regulatory, commercialization, and business development expertise of the rest of our senior management and other senior personnel across preclinical, clinical, translational medicine, legal, and regulatory affairs. If we lose one or more of our executive officers or key employees or consultants, our ability to implement our business strategy successfully could be seriously harmed. Any of our executive officers, key employees, or consultants may terminate their employment and/or engagement with us at any time. Replacing executive officers, key employees, and consultants may be difficult and may take an extended period of time because of the limited number of individuals in our industry with the breadth of skills and experience required to develop, gain regulatory approval of, and commercialize products successfully. Competition to hire and retain employees and consultants from this limited pool is intense, and we may be unable to hire, train, retain, or motivate these additional key personnel and consultants. Our failure to retain key personnel or consultants could materially harm our business.
We have scientific and clinical advisors and consultants who assist us in formulating and implementing our research, development, and clinical strategies. These advisors are not our employees and may have commitments to, or consulting or advisory contracts with, other entities limiting their availability to us and typically they will not enter into non-compete agreements with us. If a conflict of interest arises between their work for us and their work for another entity, we may lose their services. In addition, our advisors may have arrangements with other companies to assist those companies in developing products or technologies competitive with ours.

We expect a number of factors to cause our operating results to fluctuate on a quarterly and annual basis, which may make it difficult to predict our future performance.
We are a clinical -stagestage biopharmaceutical company that has beenwith a limited operating since 1998.history. Our operations to date have been primarily limited to researchingorganizing and staffing our company, acquiring, developing product candidates, including conductingand securing our proprietary technology and preclinical studies and clinical trials.development of our product candidates. We have not yet obtained regulatory approvalssuccessfully completed any clinical trials for any of our product candidates.candidates, manufactured our product candidates at commercial scale or conducted sales and marketing activities that will be necessary to successfully commercialize our product candidates, if approved. Consequently, any predictions made about our future success or viability may not be as accurate as they could be if we had a longer operating history or approved products on the market.commercialized products. Our financial condition has varied significantly in the past and operating results are expectedwill continue to significantly fluctuate from quarter-to-quarter or year-to-year due to a variety of factors, many of which are beyond our control. Factors relating to our business that may contribute to these fluctuations include but are not limited to:other factors described elsewhere herein and also include, among other things:
the timing and cost of, and level of investment in, research, development, including the needs for additional clinical trials, and, if approved, commercialization activities relating to our product candidates, which may change from time to time;
delay in or the success of our clinical trials through all phases of clinical development, including our ongoing clinical trials of ANG-3070;
potential adverse events associated with our product candidates potentially delaying or preventing approval or causing an approved drug to be taken off the market;
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any delays in regulatory review and approval by regulatory authorities of our product candidates in clinical development, including ANG-3070;
our ability to obtain additional funding to develop our product candidates;
our ability to commercializeconduct and complete nonclinical studies and clinical trials;
delays in the commencement, enrollment and timing of clinical trials;
the success of our nonclinical studies and clinical trials through all phases of development;
any delays in regulatory review and approval of product candidates in clinical development;
our ability to obtain and maintain regulatory approval for our product candidates in the United States and foreign jurisdictions;
potential toxicity and/or side effects of our product candidates that could delay or prevent commercialization, limit the indications for any approved products, require the establishment of risk evaluation and mitigation strategies, cause an approved drug to be taken off the market or an inability to establish efficacy needed for approvals;
our ability to establish or maintain partnerships, collaborations, licensing or other arrangements;
market acceptance andof our product candidates, if approved;
competition from existing products, new products or new therapeutic approaches that may emerge;
the ability of patients or health care providers to obtain coverage of or sufficient reimbursement for our approved products;
our ability to leverage our proprietary AMP technology platform to discover and develop additional product candidates;
our ability and our licensors’ abilities to successfully obtain, maintain, defend and enforce intellectual property rights important to our business; and
potential product liability claims.
Accordingly, the results of any quarterly or annual periods should not be relied upon as indications of future operating performance.
We have identified material weaknesses in our dependencyinternal control over financial reporting related to our control environment. If we do not remediate the material weaknesses in our internal control over financial reporting, or if we fail to establish and maintain effective internal control, we may not be able to accurately report our financial results, which may cause investors to lose confidence in our reported financial information and may lead to a decline in the market price of our stock.
As a public company, we are required to maintain internal control over financial reporting and to report any material weaknesses in such internal controls. Pursuant to Section 404 (“Section 404”) of the Sarbanes-Oxley Act of 2002,
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as amended (the “Sarbanes-Oxley Act”), we are required to furnish a report by our management on third-party manufacturersour internal control over financial reporting in our periodic reports filed with the SEC. However, while we remain an emerging growth company, we will not be required to manufactureinclude an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. To achieve compliance with Section 404 within the prescribed period, we will be engaged in a process to document and distributeevaluate our productsinternal control over financial reporting, which is both costly and key ingredients.challenging. In this regard, we will need to continue to dedicate internal resources, potentially engage outside consultants and adopt a detailed work plan to assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing that controls are functioning as documented and implement a continuous reporting and improvement process for internal control over financial reporting. Despite our efforts, there is a risk that we will not be able to conclude, within the prescribed timeframe or at all, that our internal control over financial reporting is effective as required by Section 404. If we identify additional material weaknesses, it could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements. A material weakness is a deficiency, or combination of deficiencies, in internal control over financial reporting, such that there is a reasonable possibility that a material misstatement of our annual or interim financial statements will not be prevented, or detected and corrected on a timely basis.

We facehave identified material weaknesses in our internal control over financial reporting related to our control environment. More specifically, we have determined that we have not maintained adequate formal accounting policies, processes and controls related to complex transactions as a result of a lack of finance and accounting staff with the appropriate U.S. generally accepted accounting principles (“U.S. GAAP”) technical expertise needed to identify, evaluate and account for complex and non-routine transactions. We have also determined that we have insufficient financial reporting and close controls to ensure that incurred expenses are accrued at period end. In addition, we have determined that we have not ensured calculations used in financial reporting are properly reviewed, including earnings per share (“EPS”) and weighted average shares outstanding (“WASO”) calculations as a result of a lack of finance and accounting staff with the appropriate U.S. GAAP technical expertise needed to identify, evaluate and review such calculations.

We have implemented, and over the next several months, we plan to implement additional measures to address the material weaknesses we have identified. We plan to design additional controls around identification, documentation and application of technical accounting guidance with particular emphasis on complex and non-routine transactions. These controls are expected to include an additional review process to ensure that the correct conclusions are reached with respect to complex and non-routine transactions and avoid the potential for a material misstatement of our financial statements. Additionally, we plan to engage SEC compliance and technical accounting consultants to assist in evaluating transactions for conformity with U.S. GAAP, as well as hire additional finance and accounting personnel to augment accounting staff and to provide more resources for complex accounting matters and financial reporting. However, we cannot assure you that we will be successful in remediating the material weaknesses we identified or that our internal control over financial reporting, as modified, will enable us to identify or avoid material weaknesses in the future.
Any failure to remediate the material weaknesses we identified or any failure to develop or maintain effective controls, or any difficulties encountered in their implementation or improvement, could harm our operating results or cause us to fail to meet our reporting obligations and may result in a restatement of our financial statements for prior periods. Any failure to remediate the material weaknesses we identified or any failure to implement and maintain effective internal control over financial reporting could also adversely affect the results of management reports and independent registered public accounting firm audits of our internal control over financial reporting that we will eventually be required to include in our periodic reports that will be filed with the SEC. Ineffective disclosure controls and procedures, and internal control over financial reporting could also cause investors to lose confidence in our reported financial and other information, which would likely have a negative effect on the market price of our common stock.
Failure to maintain effective internal controls in accordance with Section 404 of the Sarbanes-Oxley Act could have a material adverse effect on our stock price.
Section 404 of the Sarbanes-Oxley Act and the related rules and regulations of the SEC require annual management assessments of the effectiveness of our internal control over financial reporting. If we fail to maintain the adequacy of our internal control over financial reporting, as such standards are modified, supplemented or amended from time to time, we may not be able to ensure that we can conclude on an ongoing basis that we have effective internal control over financial reporting in accordance with Section 404 of the Sarbanes-Oxley Act and the related rules and regulations of the SEC. If we cannot favorably assess the effectiveness of our internal control over financial reporting, investor confidence in the reliability of our financial reports may be adversely affected, which could have a material adverse effect on our stock price.
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We hold a portion of our cash and cash equivalents that we use to meet our working capital and operating expense needs in deposit accounts that could be adversely affected if the financial institutions holding such funds fail.
We hold a portion of our cash and cash equivalents that we use to meet our working capital and operating expense needs in deposit accounts. The balance held in these accounts may exceed the Federal Deposit Insurance Corporation (“FDIC”) standard deposit insurance limit of $250,000. If a financial institution in which we hold such funds fails or is subject to significant adverse conditions in the financial or credit markets, we could be subject to a risk of loss of all or a portion of such uninsured funds or be subject to a delay in accessing all or a portion of such uninsured funds. Any loss or lack of access to these funds could adversely impact our short-term liquidity and ability to meet our operating expense obligations.
Changes in interpretation or application of U.S. GAAP may adversely affect our operating results.
We prepare our consolidated financial statements to conform to U.S. GAAP. These principles are subject to interpretation by the Financial Accounting Standards Board (“FASB”), American Institute of Certified Public Accountants, the SEC and various other regulatory and accounting bodies. A change in interpretations of, or our application of, these principles can have a significant effect on our reported results and may even affect our reporting of transactions completed before a change is announced. In addition, when we are required to adopt new accounting standards, our methods of accounting for certain items may change, which could cause our results of operations to fluctuate from period to period and make it more difficult to compare our financial results to prior periods.
Risks Related to the Development of our Product Candidates
Our product candidates are at an early stage of development and may not be successfully developed or commercialized.
In April 2023, we completed enrollment of the AMPLIFY-201 trial for ELI-002, our 2-peptide formulation, targeting Kirsten rat sarcoma viral oncogene homolog (“KRAS”) gene mutations, which product candidate also includes ELI-004, our universal AMP-modified CpG adjuvant. In October 2023, we completed enrollment of the AMPLIFY-7P Phase 1 portion of the trial for ELI-002, our 7-peptide formulation, and initiated enrollment of the AMPLIFY-7P Phase 2 portion of the trial in January 2024. We have not previously conducted clinical trials with our product candidates. All of our other product candidates are in preclinical development and will require substantial further capital expenditures, development, testing, and regulatory approval prior to commercialization. With the limited data on ELI-002, we may not be able to effectively design and execute clinical studies that ultimately support marketing approval. In addition, we have not initiated or submitted for any marketing authorization to any health authorities.
The time required to obtain approval from the FDA and comparable foreign authorities is unpredictable but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including the substantial discretion of regulatory authorities. The outcome of studies is also inherently uncertain. Of the large number of drugs in development, only a small percentage successfully complete the regulatory approval process and are commercialized. The results of nonclinical studies, interim or top-line study results, and early clinical trials of our product candidates may not be predictive of the results of later-stage clinical trials. Failure can occur at any time during the clinical trial process. Product candidates in later stages of clinical trials may fail to show the desired safety and efficacy despite having progressed through nonclinical studies and initial clinical trials. Nonclinical and early clinical studies may also reveal unfavorable product candidate characteristics, including safety concerns. A number of companies have suffered significant setbacks in advanced clinical trials, notwithstanding promising results in earlier trials. In some instances, there can be significant variability in results between different clinical trials of the same product candidate due to numerous factors, including, among other things, differences in trial procedures set forth in protocols, differences in the type of the patient populations, changes in and adherence to the clinical trial protocols, the rate of dropout among clinical trial participants, and evolving standards of treatment from newly approved drugs.
Accordingly, even if we are able to obtain the requisite financing to fund our development programs, we cannot assure you that our product candidates will be successfully developed or commercialized. Our failure to develop, manufacture or receive regulatory approval for or successfully commercialize any of our product candidates could result in the failure of our business and a loss of all of our stockholders’ investment.
Our product candidates are in various stages of development and we will not be able to commercialize our product candidates if our nonclinical and clinical studies do not produce successful results and/or our clinical trials do not demonstrate the safety and efficacy of our product candidates; early results and early understanding of product candidate potential may not be predictive of later success. Any product candidates currently in clinical development or that we advance into clinical development are subject to extensive regulation, which can be costly and time-consuming, and we may experience unanticipated delays or be unable to receive the required approvals to commercialize our product candidates.
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Product candidates are susceptible to the risks of failure inherent at any stage of product development, including the occurrence of unexpected or unacceptable adverse events or the failure to demonstrate efficacy in clinical trials. Clinical development is expensive and can take many years to complete, and its outcome is inherently uncertain. The results of nonclinical studies, preliminary clinical trial results, and early clinical trials of our product candidates may not be predictive of the results of later-stage clinical trials. Our product candidates may not perform as we expect, may ultimately have a different than expected impact or no impact at all, may have a different mechanism of action than we initially understand or than we expect in humans, and may not ultimately prove to be safe or effective.
The nonclinical and clinical development, manufacturing, packaging, labeling, storage, record-keeping, advertising, promotion, post-approval monitoring and reporting, import, export, marketing and distribution, among other activities, of our product candidates are subject to extensive regulation by the FDA and by comparable health authorities in foreign markets. We are not permitted to market or promote our product candidates in the United States until we receive approval from the FDA of a Biologics License Application (“BLA”), or in any jurisdictions outside of the United States until we receive similar authorization from analogous foreign authorities, and we may never receive such regulatory approvals for any of our product candidates.
Some of our product candidates have only been tested in a nonclinical setting and while those studies have been subject to certain regulatory requirements in order to support product development and regulatory progression, as such product candidates progress they will require clinical trials (which are subject to much more extensive requirements, including good clinical practice standards), as well as additional manufacturing development, before we will be able to submit marketing applications to the applicable regulatory authorities. Even if our product candidates are approved, they may be subject to limitations on the indicated uses and populations for which they may be marketed. They may also be subject to other conditions of approval, may contain significant safety warnings, including boxed warnings, contraindications, and precautions, may not be approved with label statements necessary or desirable for successful commercialization, or may contain requirements for costly post-market testing and surveillance, or other requirements, including the submission of a risk evaluation and mitigation strategy (“REMS”) to monitor the safety or efficacy of the products. If we do not receive regulatory authority approval for, and successfully commercialize our product candidates, we will not be able to generate revenue from these product candidates in the foreseeable future, or at all. Any significant delays in obtaining approval for and commercializing our product candidates could have a material adverse impact on our business and financial condition.
The process of product candidate development and obtaining marketing approval is expensive, often takes many years and can vary substantially based upon the type, complexity and novelty of the products involved and the conditions that they are intended to treat. The number and nature of nonclinical studies and clinical trials that will be required for regulatory approval also varies depending on the product candidate, the disease or condition that the product candidate is designed to address and the regulations applicable to any particular product candidate. We have not previously submitted a marketing application to the FDA, or a similar marketing application to any comparable foreign authorities, for any product candidate, and we cannot be certain that our product candidates will be successful in clinical trials or receive regulatory approval.
In addition to significant clinical testing requirements, our ability to obtain marketing approval for our product candidates depends on obtaining the final results of required nonclinical testing, including characterization of the manufactured components of our product candidates and validation of our manufacturing processes. Regulatory authorities may determine that our product manufacturing processes, testing procedures or facilities are insufficient to justify approval. Approval policies or regulations, or the type and amount of data necessary to gain approval, may change and may vary among jurisdictions. Moreover, regulatory authorities have substantial discretion in the biopharmaceutical approval process, including the ability to refuse to accept an application and to delay, limit or deny approval of a product candidate for many reasons, such as a determination that our data is insufficient for approval or that additional nonclinical studies, clinical trials or other data or development work is necessary. Despite the time and expense invested in the development of product candidates, regulatory approval is never guaranteed.
Our product candidates may fail at any stage of preclinical or clinical development, and may also reveal unfavorable product candidate characteristics, including safety concerns or the failure to demonstrate efficacy in initial clinical trials. Further, our product candidates may not receive regulatory approval even if they are successful in clinical trials. Although we have completed preclinical validation, including toxicology testing, and anticipate completing the preclinical development necessary to file additional Investigational New Drug (“IND”) applications for other product candidates in the future, we may experience numerous unforeseen events before, during, or as a result of clinical trials that could delay or prevent our ability to commence or complete development, commence or complete clinical trials, receive marketing approval or commercialize our product candidates, including:
we may be unable to generate sufficient nonclinical, toxicology, or other in vivo or in vitro data to support the initiation of clinical trials;
regulators or institutional review boards (“IRBs”) or Independent Ethics Committees (“IECs”) may not authorize us or our investigators to commence or continue a clinical trial, conduct a clinical trial at a
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prospective trial site, or amend trial protocols, or may require that we modify or amend our clinical trial protocols;
we, regulators, independent data monitoring committees (“IDMC”), IRBs, or IECs may recommend or require the suspension or termination of clinical research for various reasons, including non-compliance with regulatory requirements or a finding that participants are being exposed to unacceptable health risks, undesirable side effects, or a failure of the product candidate to demonstrate any benefit to subjects, or other unexpected characteristics (alone or in combination with other products) of the product candidate, or due to findings of undesirable effects caused by a chemically or mechanistically similar therapeutic or therapeutic candidate;
new information may emerge regarding our product candidates or technology platform that result in continued development of some or all of our product candidates being deemed undesirable;
we may have delays identifying, recruiting and training suitable clinical investigators or investigators may withdraw from our studies;
we may experience delays in reaching, or failing to reach, agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites or contract research organizations (“CROs”). Contractual terms can be subject to extensive negotiation, may be subject to modification from time to time and may vary significantly among different CROs and trial sites;
we may have delays in adding new clinical trial sites, or we may experience a withdrawal of clinical trial sites;
potential delays in patient enrollment for clinical trials due to public health emergencies pandemics, natural disasters, staffing shortages, or other events, which may affect our ability to initiate, conduct ongoing clinical trials, and delay initiation of planned and future clinical trials;
the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate, or participants may drop out of these clinical trials or be lost to follow-up at a higher rate than we anticipate for a number of reasons, such as adverse events, lack of treatment effectiveness, fatigue with the clinical trial process or personal issues, electing to participate in alternative clinical trials sponsored by our competitors with product candidates that treat the same indications as our product candidates;
patients who enroll in our studies may misrepresent their eligibility or may otherwise not comply with clinical trial protocols, resulting in the need to increase the enrollment size for those studies, or extend the duration of those studies;
there may be flaws in our study design, which may not become apparent until a study is well advanced;
our contractors may fail to comply with regulatory requirements or clinical trial protocols, or meet their contractual obligations to us in a timely manner, or at all, or we may be required to engage in additional clinical trial site monitoring;
regulatory authorities or IRBs or IECs may disagree with the design, including endpoints, scope, or implementation of our clinical trials, or regulatory authorities may disagree with the study patient population against our intended indications or our interpretation of data from nonclinical studies or clinical trials;
regulatory authorities may disagree with the formulation for our product candidates, or our product candidate dose or dosing schedule;
we may be unable to demonstrate to the satisfaction of regulatory authorities that a product candidate is safe, pure, and potent for any indication;
regulatory authorities may not accept, or we or our clinical trials may not meet, the criteria required to submit, clinical data from trials which are conducted outside of their jurisdictions;
the results of clinical trials may be negative or inconclusive, may not meet the level of statistical significance required for, or may not otherwise be sufficient to support marketing approval, and we may decide, or regulatory authorities may require it, to conduct additional clinical trials, analyses, reports, data, or nonclinical studies, or abandon product development programs;
our product candidates may have undesirable or unintended side effects, toxicities, or other properties or characteristics that preclude marketing approval or prevent or limit commercial use;
we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks or otherwise provide an advantage over current standard of care (“SOC”) or current or future competitive therapies in development;
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the SOC for the indications we are investigating may change, which changes could impact the meaningfulness of our resulting study data or which may necessitate changes to our studies;
regulatory authorities may disagree with our scope, design, including endpoints, implementation, or our interpretation of data from nonclinical studies or clinical trials;
regulatory authorities may require us to amend our studies, perform additional or unanticipated clinical trials or nonclinical studies or manufacturing development work to obtain approval or initiate clinical trials, or we may decide to do so or abandon product development programs;
regulatory authorities may find that we or our third-party manufacturers do not satisfy regulatory requirements and standards for the facilities and operations used in the manufacture of our product candidates;
the cost of clinical trials of our product candidates may be greater than we anticipate, or we may have insufficient funds for a clinical trial or to pay the substantial user fees required by the FDA or other regulatory authorities upon the filing of a marketing application;
the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates may be insufficient or inadequate;
regulatory authorities may take longer than we anticipate to make a decision on our product candidates;
we may be unable to demonstrate the efficacy and safety of our product candidates to the FDA or other regulatory authorities, due to inaccurate or inconsistent potency assessments, potentially resulting in regulatory delays, additional testing requirements, or even rejection of our product candidates;
changes in regulatory guidelines of the FDA or other regulatory authorities may necessitate modifications to any future biological potency assays we may develop, requiring additional validation studies and potential delays in the development or commercialization of our product candidates; or
changes in or the enactment of the approval policies, statutes, or regulations of the applicable regulatory authorities may significantly change in a manner rendering our nonclinical or clinical data insufficient for approval.
Additionally, our clinical trials, to date, have been open-label trials. Our Phase 2 study of AMPLIFY-7P is an open-label, randomized study, where both the patient and investigator know whether the patient is receiving our product candidate or is under observation, which may introduce study bias. Most typically, open-label clinical trials test only the product candidate and sometimes do so at different dose levels. Open-label clinical trials are subject to various limitations that may exaggerate any therapeutic effect as patients in open-label clinical trials are aware when they are receiving treatment. In addition, open-label clinical trials may be subject to an “investigator bias” where those assessing and reviewing the physiological outcomes of the clinical trials are aware of which patients have received product candidate and may interpret the information of the treated group more favorably given this knowledge. Positive results observed in open-label trials may not be replicated in later clinical trials. Additionally, as patients become aware that they are not receiving our product candidate as part of the trial, they may elect to withdraw from our study and enroll in clinical trials sponsored by our competitors, which may extend our study timeline.
Furthermore, we expect to rely on CROs and clinical trial sites to ensure the proper and timely conduct of our clinical trials and, while we expect to enter into agreements governing their committed activities, we have limited influence over their actual performance.
A clinical trial may be suspended or terminated by us, our partners, the IRBs of the institutions in which such trials are being conducted, the IDMC for such trial or by the FDA or other regulatory authorities due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a drug or therapeutic biologic, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial. If we experience delays in the completion of, or termination of, any clinical trial of any of our potential future product candidates, the commercial prospects of such product candidate will be harmed, and our ability to generate product revenue from such product candidates will be delayed. In addition, any delays in completing our clinical trials will increase our costs, slow our product development and approval process and jeopardize our ability to commence product sales and generate revenue, and we may not have the financial resources to continue development of the product candidate that is affected or any of our other product candidates. We may also lose, or be unable to enter into, collaborative arrangements for the affected product candidate and for other product candidates that we are developing. Any of these occurrences may materially and adversely affect our business, financial condition, results of operations and prospects. In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our potential future product candidates.
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Preliminary results from our nonclinical studies and clinical trials that we announce or publish from time to time may change as more patient data becomes available and as the data undergoes audit and verification procedures.
From time to time, we may publish interim, topline, or preliminary results from our nonclinical studies and clinical trials. Preliminary and interim results from our clinical trials are not necessarily predictive of final results and are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available. Preliminary, interim and topline data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, preliminary, interim and topline data should be viewed with caution until the final data are available. Material adverse changes in the final data compared to the preliminary, interim or topline data could significantly harm our business prospects.
Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate or therapeutic product, if any, and us in general. In addition, the information we choose to publicly disclose regarding a particular nonclinical study or clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine is the material or otherwise appropriate information to include in our disclosure, and any information we determine not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise regarding a particular therapeutic product, if any, product candidate or our business. If the preliminary, interim and topline data that we report differs from actual results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain approval for, and commercialize, our product candidates may be harmed, which could harm our business, operating results, prospects or financial condition.
The FDA or comparable foreign regulatory authorities may disagree with our regulatory plans and we may fail to obtain regulatory approval of our product candidates.
The FDA standard for approval of a biologic generally requires two adequate, well-controlled clinical trials, each convincingly demonstrating the product candidate’s safety and effectiveness, or one large and robust, well-controlled trial providing substantial evidence that the product candidate is safe and effective for its proposed indication. Phase 3 clinical trials typically involve hundreds of patients, have significant costs and take years to complete. Product candidates studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may be eligible for accelerated approval and may be approved on the basis of adequate and well-controlled clinical trials establishing that the product candidate has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments. As a condition of accelerated approval, the FDA usually requires a sponsor of a drug or biologic receiving accelerated approval to perform post-marketing studies to verify and describe the predicted effect on irreversible morbidity or mortality or other clinical endpoint, and the drug or biologic may be subject to withdrawal procedures by the FDA that are more accelerated than those available for regular approvals.
Our clinical trial results may not support either accelerated or regular approval. The results of nonclinical studies and clinical trials may not be predictive of the results of later-stage clinical trials, and product candidates in later stages of clinical trials may fail to show the desired safety and efficacy despite having progressed through nonclinical studies and initial clinical trials. In addition, our product candidates could fail to receive regulatory approval for many reasons, including the following:
the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials;
the population studied in the clinical program may not be sufficiently broad or representative to assure safety in the full population for which we seek approval;
the results of clinical trials may not meet the level of statistical significance required by the FDA or comparable foreign regulatory authorities for approval;
we may be unable to demonstrate that the clinical and other benefits of our product candidates outweigh their safety risks;
we may be unable to demonstrate that our product candidates’ risk-benefit ratios for their proposed indications are acceptable;
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the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from nonclinical studies or clinical trials;
the data collected from clinical trials of our product candidates may not be sufficient to satisfy the FDA or comparable foreign regulatory authorities or to support the submission of a BLA or other comparable submission in foreign jurisdictions or to obtain regulatory approval in the United States or elsewhere;
the FDA or comparable foreign regulatory authorities may fail to approve the manufacturing processes, our own manufacturing facilities, or a third-party manufacturer’s facilities with which we contract for clinical and commercial supplies;
the FDA or comparable foreign regulatory authorities may fail to approve our analytical testing methods, particularly with respect to bioassay potency testing;
we may fail to develop a potency assay for ELI-002 that is satisfactory for the FDA or comparable foreign regulatory authorities; and
the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.

Failure to obtain regulatory approval to market any of our product candidates would significantly harm our business, results of operations, and prospects.

We may not be successful in our efforts to use and expand our discovery engine to build a pipeline of product candidates.
A key element of our strategy is to use and expand our discovery engine to build a pipeline of product candidates and progress these product candidates through preclinical and clinical development for the treatment of various diseases. Although our research efforts to date suggest that complex amphiphilic molecules can deliver conventional immunomodulatory payloads including peptides, proteins and nucleic acids directly and preferentially to lymph nodes, this hypothesis may prove incorrect, or we may not be able to identify a product candidate that is safe or effective as a treatment for various cancers or for other diseases. We also may not be able to identify an amphiphile product candidate that we can demonstrate to be safe or effective, and we may not be able to develop any other product candidates. Our scientific research that forms the basis of our efforts to discover product candidates based on our discovery engine is ongoing. Further, the scientific evidence to support the feasibility of developing viable product candidates based on our platform has not been established. Our discovery engine may not be proven to be superior to competing technologies.
Even if we are successful in building our pipeline of product candidates, the potential product liability exposure,candidates that we identify may not be suitable for clinical development or generate acceptable clinical data, including as a result of being shown to have unacceptable toxicity or other characteristics that indicate that they are unlikely to be products that will receive marketing approval from the FDA or other regulatory authorities or achieve market acceptance. Investment in biopharmaceutical product development involves significant risk that any potential product candidate will fail to demonstrate adequate efficacy or an acceptable safety profile, gain regulatory approval, and ifbecome commercially viable. We cannot provide you any assurance that we will be able to successfully advance any of these additional product candidates through the development process. Our research programs may initially show promise in identifying potential product candidates, yet fail to yield product candidates for clinical development or commercialization for many reasons, including the following:
our platform may not be successful claims are brought against us, in identifying additional product candidates;
we may incur substantial liabilitynot be able or willing to assemble sufficient resources to acquire or discover additional product candidates;
our product candidates may not succeed in nonclinical or clinical testing;
a product candidate may upon further study demonstrate harmful side effects or other characteristics that indicate it is unlikely to be effective or otherwise does not meet applicable regulatory criteria;
competitors may develop alternatives that render our product candidates obsolete or less attractive;
product candidates we develop may nevertheless be covered by third parties’ patents or other exclusive rights;
the market for a product candidate may change during our program so that the continued development of that product candidate is no longer reasonable;
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a product candidate may not be capable of being produced in commercial quantities at an acceptable cost, or at all; and
a product candidate may not be accepted as safe and effective by patients, the medical community or third-party payors, if applicable.
If any of these events occur, we may be forced to abandon our development efforts for a program or programs, or we may not be able to identify, discover, develop, or commercialize additional product candidates, which would have a material adverse effect on our business and could potentially cause us to cease operations. Even if we receive FDA approval to market additional product candidates, whether for the treatment of cancers or other diseases, we cannot assure you that any such product candidates will be successfully commercialized, widely accepted in the marketplace or more effective than other commercially available alternatives.
Our ELI-002 clinical trials are designed to require, as part of screening to determine whether subjects meet inclusion criteria, the use of an investigational in vitro diagnostic device. If we are not able to successfully collaborate or partner with a third-party company for the development and authorization of such a device, we may not be able to receive marketing authorization for ELI-002.
The clinical trials for ELI-002 (AMPLIFY-201 and AMPLIFY-7P) employ an investigational in vitro diagnostic device (“IVD”), that identifies gene mutations in KRAS and neuroblastoma rat sarcoma viral oncogene homolog (“NRAS”) genes and detects circulating tumor DNA (“ctDNA”), to identify patients who show signs of minimal residual disease in their blood, but before relapse is detected in traditional radiographic scans. Based on our Phase 1 and Phase 2 study design, we must account for and address the investigational status of this device from a regulatory perspective through the course of clinical development (for example, through the compliance with any applicable investigational device exemption requirements). An IVD used to select patients who may be appropriate to receive our commercial product will be considered a companion diagnostic device. Companion diagnostic devices are subject to regulation by the FDA and comparable foreign regulatory authorities as medical devices and we anticipate that separate regulatory marketing authorization will be required for the device prior to commercialization of ELI-002. We plan to collaborate with appropriate companion diagnostic developers to seek marketing authorization from the FDA’s Center for Devices and Radiological Health (“CDRH”). If our companion diagnostic partner experiences any delays in development or is not able to successfully develop and obtain marketing authorization for its companion diagnostic, or does not comply with the FDA’s medical device regulations:
the development and commercialization of ELI-002 may also be delayed because in most circumstances, FDA expects the companion diagnostic and its corresponding therapeutic product to be approved contemporaneously by the FDA;
ELI-002 may not receive marketing approval if its safe and effective use depends on a companion diagnostic and none is commercially available; and
We may not realize the full commercial potential of ELI-002 if it receives marketing approval and, among other reasons, we are unable to appropriately identify patients or types of tumors with the specific genetic alterations targeted by ELI-002.
Even if ELI-002 and any associated companion diagnostics are approved for marketing, the need for companion diagnostics may slow or limit adoption of ELI-002. Although we believe genetic testing is becoming more prevalent in the diagnosis and treatment of cancer, ELI-002 may be perceived negatively compared to alternative treatments that do not require the use of companion diagnostics, either due to the additional cost of the companion diagnostic or the need to complete additional procedures to identify relevant biomarkers prior to administering our product candidates.
If any of these events were to occur, our business and growth prospects would be harmed, possibly materially.
We may seek designations under FDA programs designed to facilitate and potentially expedite product candidate development, such as fast track or breakthrough therapy designation. Our product candidates may not receive any such designations or if they do receive such designations it may not lead to faster development or regulatory review or approval and it does not increase the likelihood that its product candidates will receive marketing approval.
We may seek designations under the FDA’s expedited programs for serious conditions, such as fast track or breakthrough therapy designation, which are intended to facilitate and expedite the development or regulatory review or approval process for product candidates. Descriptions of the fast track and breakthrough therapy designations are included under “Description of Our Business—Government Regulation and Product Approval—Fast Track, Breakthrough Therapy and Priority Review Designations.”
The granting of fast track or breakthrough therapy designation to an investigational product is entirely within the FDA’s discretion. Accordingly, even if we believe one of our product candidates meets the criteria for a designation, the FDA may disagree and instead determine not to grant such designation. In any event, the receipt of a fast track
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or breakthrough therapy designation for a product candidate may not result in a faster development process, review, or approval compared to product candidates considered for approval under conventional FDA procedures and does not assure ultimate marketing approval by the FDA. In addition, the FDA may later decide that the product candidate no longer meets the designation conditions, in which case any granted designations may be revoked, or the agency may decide that the time period for review or approval of the product candidate will not be shortened.
If we are unable to obtain approval via the accelerated approval pathway, we may be required to conduct additional nonclinical studies or clinical trials. Even if we receive accelerated approval from the FDA, the FDA may seek to withdraw accelerated approval.
We may seek an accelerated approval development pathway for our product candidates. See “Description of Our Business—Government Regulation and Product Approval—Accelerated Approval” for a description of the accelerated approval pathway.
If we choose to pursue accelerated approval, we intend to seek feedback from the FDA or will otherwise evaluate our ability to seek and receive such accelerated approval. After our evaluation of the feedback from the FDA or other factors, we may decide not to pursue or submit a BLA for accelerated approval or any other form of expedited development, review or approval. Furthermore, if we submit an application for accelerated approval, there can be no assurance that such application will be accepted or that approval will be granted on a timely basis, or at all. The FDA also could require us to conduct further studies or trials prior to considering our application or granting approval of any type, and may require us to have a confirmatory trial to verify the clinical benefit of the product underway and partially or fully enrolled before granting approval. We might not be able to fulfill the FDA’s requirements in a timely manner, which would cause delays, or approval might not be granted because our submission is deemed incomplete by the FDA.
Even if we receive accelerated approval from the FDA, we will be subject to rigorous post-marketing requirements, including the completion of confirmatory post-market clinical trials, submission to the FDA of periodic progress reports on confirmatory trials, and submission to the FDA of all promotional materials prior to their dissemination. The FDA could seek to withdraw accelerated approval for multiple reasons, including if we fail to conduct any required post-market study with due diligence; a post-market study does not confirm the predicted clinical benefit; other evidence shows that the product is not safe or effective under the conditions of use; or we disseminate promotional materials that are found by the FDA to be false and misleading. Under the Consolidated Appropriations Act for 2023, the FDA may use expedited procedures to withdraw any product for which we receive accelerated approval if our confirmatory trials fail to verify the purported clinical benefits.
A failure to obtain accelerated approval or any other form of expedited development, review or approval for a product candidate that we may choose to develop would delay our commercialization of such product candidate, could increase the cost of development of such product candidate and could harm our competitive position in the marketplace.
If we apply for orphan drug designation from the FDA, there is no guarantee that we will be able to obtain or maintain this designation, receive this designation for any of our other product candidates, or receive or maintain any corresponding benefits, including periods of exclusivity.
Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, defined as a disease or condition with a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States when there is no reasonable expectation that the cost of developing and making available the drug or biologic in the United States will be recovered from sales in the United States for that drug or biologic. Orphan drug designation for a biologic must be requested before submitting a BLA. In the United States, orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages, and user-fee waivers. After the FDA grants orphan drug designation, the generic identity of the drug and its potential orphan use are disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.
If a biologic that has orphan drug designation subsequently receives the first FDA approval for a particular active ingredient for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a BLA, to market the same biologic for the same indication for seven years, except in limited circumstances such as a showing of clinical superiority to the product with orphan drug exclusivity or if FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the product was designated. As a result, even if one of our product candidates receives orphan exclusivity, the FDA can still approve other drugs or biologics that have a different active ingredient for use in treating the same indication or disease. Furthermore, the FDA can waive orphan exclusivity if we are unable to manufacture sufficient supply of our product.
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We may seek orphan drug designation for some or all of our product candidates in specific orphan indications for which there is a medically plausible basis for their use, but exclusive marketing rights in the United States may be limited if we seek approval for an indication broader than the orphan designated indication and may be lost if the FDA later determines that the request for designation was materially defective or if we are unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition. In addition, although we intend to seek orphan drug designation for other product candidates, we may never receive such designations.
We may expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.
Because we have limited financial and managerial resources, we focus on research programs and product candidates that we identify for specific indications. As a result, we may forego or delay pursuit of opportunities with other product candidates or for other indications that later prove to have greater commercial potential. Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities. Our spending on current and future research and development programs and product candidates for specific indications may not yield any commercially viable products. If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidate.
Any future product candidates for which we intend to seek approval as biological products may face competition sooner than anticipated.
Even if we are successful in achieving regulatory approval to commercialize a product candidate ahead of our competitors, our product candidates may face competition from biosimilar products. In the United States, our amphiphile product candidates are expected to be regulated by the FDA as biological products, and we intend to seek approval for these product candidates pursuant to the BLA pathway. The enactment of the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) created an abbreviated pathway for the approval of biosimilar and interchangeable biological products based on a previously licensed reference product. Under the BPCIA, an application for a biosimilar biological product cannot be approved by the FDA until 12 years after the original reference biological product was approved under a BLA. The law is complex and is still being interpreted and implemented by the FDA. As a result, its ultimate impact, implementation, and meaning are subject to uncertainty. While it is uncertain when such processes intended to implement BPCIA may be fully adopted by the FDA, any such processes could have a material adverse effect on the future commercial prospects for our product candidates.
We believe that any of our product candidates approved as a biological product under a BLA should qualify for the 12-year period of exclusivity available to reference biological products. However, there is a risk that this exclusivity could be shortened due to congressional action or otherwise, or that the FDA will not consider our product candidates to be reference biological products pursuant to its interpretation of the exclusivity provisions of the BPCIA for competing products, potentially creating the opportunity for generic follow-on biosimilar competition sooner than anticipated. Moreover, the extent to which a biosimilar product, once approved, will be substituted for any one of our reference products in a way that is similar to traditional generic substitution for non-biological products is not yet clear, and will depend on a number of marketplace and regulatory factors that are still developing including whether a future competitor seeks an interchangeability designation for a biosimilar of one of our products. Under the BPCIA as well as state pharmacy laws, only interchangeable biosimilar products are considered substitutable for the reference biological product without the intervention of the health care provider who prescribed the original biological product. However, as with all prescribing decisions made in the context of a patient-provider relationship and a patient’s specific medical needs, health care providers are not restricted from prescribing biosimilar products in an off-label manner. In addition, a competitor could decide to forego the abbreviated approval pathway available for biosimilar products and to submit a full BLA for product licensure after completing its own nonclinical studies and clinical trials. In such a situation, any exclusivity for which our products candidates may be eligible under the BPCIA would not prevent the competitor from marketing a product similar or identical to our biological product as soon as it is approved.
In Europe, the European Commission has granted marketing authorizations for several biosimilar products pursuant to a set of general and product class-specific guidelines for biosimilar approvals issued over the past few years. In addition, companies may be developing biosimilar products in other countries that could compete with our products, if approved.
If competitors are able to obtain marketing approval for biosimilars referencing our product candidates, our future products may become subject to competition from such biosimilars, whether or not they are designated as interchangeable, with the attendant competitive pressure and potential adverse consequences. Such competitive products may be able to immediately compete with us in each indication for which our product candidates may have received approval.
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If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected.
We may experience difficulties in patient enrollment in our clinical trials for a variety of reasons. The timely completion of clinical trials in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of subjects who remain in the trial until its conclusion. We may not be able to initiate or continue conducting clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible subjects to participate in these trials. The enrollment of patients depends on many factors, including:
the number of clinical trials for other product candidates in the same therapeutic area that are currently in clinical development, and our ability to compete with such trials for subjects and clinical trial sites;
the severity of the disease under investigation and the existence of current treatments;
the perceived risks and benefits of the product candidate, including the potential advantages or disadvantages of the product candidate being studied in relation to other available therapies;
the subject eligibility criteria defined in the protocol, as well as our ability to compensate subjects for their time and effort;
the size and nature of the patient population;
the proximity and availability of clinical trial sites for prospective subjects;
the design of the trial, including factors such as frequency of required assessments, length of the study and ongoing monitoring requirements;
subjects’ and investigators’ ability to comply with the specific instructions related to the trial protocol, proper documentation, and use of the product candidate;
our ability to recruit clinical trial investigators with the appropriate competencies and experience;
patient referral practices of physicians and the effectiveness of publicity created by clinical trials sites regarding the trial;
the ability to adequately monitor subjects during and after treatment and compensate them, as applicable, for their time and effort;
the ability of our clinical study sites, CROs, and other applicable third parties to facilitate timely enrollment;
the ability of clinical trial sites to enroll subjects that meet all inclusion criteria and any patient exclusion due to erroneous enrollment;
our ability to obtain and maintain subject informed consents;
the ability of clinical trial sites to enroll patients due to public health emergencies or pandemics, natural disasters, staffing shortages, or other events; and
the risk that subjects enrolled in clinical trials will drop out of the trials before completion of the study or not return for post-study follow-up, especially subjects in control groups, due to reasons such as, adverse events, lack of treatment effectiveness, fatigue with the clinical trial process or personal issues, electing to participate in alternative clinical trials sponsored by our competitors with product candidates that treat the same indications as our product candidates.
In addition, our clinical trials will compete with other clinical trials for product candidates that are in the same therapeutic areas as our product candidates, and this competition will reduce the number and types of patients available to us, because some patients who might have opted to enroll in our trials may instead opt to enroll in a trial being conducted by one of our competitors. Because the number of qualified clinical investigators is limited, we may conduct some of our clinical trials at the same clinical trial sites that some of our competitors use, which will reduce the number of patients who are available for our clinical trials at such clinical trial sites. Moreover, because our product candidates represent a departure from more commonly used methods for cancer treatment, potential patients and their doctors may be inclined to use conventional therapies, such as chemotherapy, rather than enroll patients in any of our future clinical trials.
Our inability to enroll a sufficient number of subjects for our clinical trials would result in significant delays and could require us to abandon one or more clinical trials altogether. Moreover, a significant number of withdrawn subjects would compromise the quality of our data. Enrollment delays in our clinical trials may result in increased development costs for our product candidates, or the inability to complete development of our product candidates, which could cause our value to decline, limit its commercialization.our ability to obtain additional financing, and materially impair our ability to generate revenues.
The
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Any product candidate we advance into clinical trials may cause unacceptable adverse events or have other properties that may delay or prevent our regulatory approval or commercialization or limit our commercial potential.
As with most biological products, use of our product candidates could be associated with side effects or adverse events, which can vary in severity from minor reactions to death and in frequency from infrequent to prevalent. Undesirable side effects caused by any current or future product candidate could cause regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the saledelay or denial of regulatory approval by the FDA or other regulatory authorities. We initiated dosing of the AMPLIFY-201 trial of our 2-peptide formulation of ELI-002 in October 2021, our 7-peptide formulation of ELI-002, the AMPLIFY-7P trial, began dosing in April 2023. We initiated enrollment of the Phase 2 of the AMPLIFY-7P trial in January 2024 and we have not yet initiated clinical trials for any other product candidates. ELI-002, through the course of the AMPLIFY-201 and AMPLIFY-7P trials to date, has shown to induce mild to moderate side effects, such as fatigue, malaise, injections site reactions and myalgia. If we initiate future clinical trials for any other current or future product candidates or continue to advance the AMPLIFY-201 or AMPLIFY-7P studies, it is likely that there will be new or additional side effects associated with the use of our product candidates. Results of our clinical trials could reveal a high and unacceptable severity and prevalence of these side effects. In such an event, our trials could be suspended or terminated, and the FDA or other regulatory authorities could place a clinical hold or order us to cease further development of or deny approval of a product candidate for any or all targeted indications. Such side effects could also affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Any of these occurrences may materially and adversely affect our business and financial condition and impair our ability to generate revenues.
Further, clinical trials by their nature utilize a sample of the potential patient population. With a limited number of patients and limited duration of exposure, rare and severe side effects of a product candidate may only be uncovered when a significantly larger number of patients are exposed to the product candidate or when patients are exposed for a longer period of time.
If one or more of our product candidates receives marketing approval, and we or others later identify undesirable side effects caused by such products, including during any long-term follow-up observation period recommended or required for patients who receive treatment using our products, a number of potentially significant negative consequences could result, including:
regulatory authorities may withdraw or limit their approvals of such products;
regulatory authorities may require the addition of labeling statements, specific warnings or contraindications;
we may be required to create a REMS plan, which could include a medication guide outlining the risks of such side effects for distribution to patients, a communication plan for health care providers, and/or other elements to assure safe use;
we may be required to change the way such products are distributed or administered, or change the labeling of the products;
the FDA or a comparable foreign regulatory authority may require us to conduct additional clinical trials or costly post-marketing testing and surveillance to monitor the safety and efficacy of the products;
we may decide to recall such products from the marketplace after they are approved;
we could be sued and held liable for harm caused to individuals exposed to or taking our products; and
our reputation may suffer.
In addition, adverse side effects caused by any therapeutics that may be similar in nature to our product candidates could delay or prevent regulatory approval of our product candidates, limit the commercial profile of an approved label for our product candidates, or result in significant negative consequences for our product candidates following marketing approval.
Any of these events could prevent us from achieving or maintaining market acceptance of the affected product candidates and could substantially increase the costs of commercializing our product candidates, if approved, and significantly impact our ability to successfully commercialize our product candidates and generate revenues.
We may form or seek strategic partnerships or enter into additional licensing arrangements in the future, and we may not realize the benefits of such alliances or licensing arrangements.
From time to time, we may form or seek strategic partnerships or collaborations or enter into additional licensing arrangements with third parties that we believe will complement or augment our development and commercialization efforts with respect to our product candidates and any future product candidates that we may
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develop. Any such relationships may require us to incur non-recurring and other charges, increase our near and long-term expenditures, issue securities that dilute our existing stockholders or disrupt our management and business. These relationships also may result in a delay in the development of our product candidates if we become dependent upon the other party and such other party does not prioritize the development of our product candidates relative to our other development activities. Additionally, any collaborations, or licensing arrangements would be subject to the same product candidate development and compliance risks and obligations as we would be if we were to develop the product candidate on our own. Should any third party with which we enter into any of these arrangements not comply with the applicable regulatory requirements, we or they may obtainbe subject to regulatory enforcement action and we or they may be delayed or prevented from obtaining marketing approval for the applicable product candidate. Any collaborations, or licensing arrangements may pose a number of risks, including the following:
any third party with which we enter into any of these arrangements often have significant discretion in determining the efforts and resources that they will apply to the arrangement and may not commit sufficient resources to the development, marketing or commercialization of the product or products that are subject to the arrangement;
third parties may not perform their obligations as expected or may breach or terminate their agreements with us or otherwise fail to conduct their collaborative or licensing activities successfully and in a timely manner;
any such collaboration, partnership, or licensing arrangement may significantly limit our share of potential future profits from the associated program, and may require us to relinquish potentially valuable rights to our current product candidates, potential products or proprietary technologies or grant licenses on terms that are not favorable to us;
third parties may cease to devote resources to the development or commercialization of our product candidates if the partners view our product candidates as competitive with their own products or product candidates;
disagreements with third parties, including disagreements over proprietary rights, contract interpretation or the course of development, might cause delays or termination of the development or commercialization of product candidates, and might result in legal proceedings, which would be time consuming, distracting and expensive;
third parties may be impacted by changes in their strategic focus or available funding, or business combinations involving them, which could cause them to divert resources away from the arrangement;
third parties may infringe the intellectual property rights of other third parties, which may expose us to litigation and potential liability;
the collaborations, partnerships, or licensing arrangements may not result in us achieving revenues sufficient to justify such transactions;
by entering into certain collaborations, partnerships, or licensing arrangements, we may forego opportunities to collaborate with other third parties who do not wish to be associated with our existing third-party strategic partners; and
such arrangements may be terminated and, if terminated, may result in a need for us to raise additional capital to pursue further development or commercialization of the applicable product candidate.
In addition, we face significant competition in seeking appropriate strategic partners and the negotiation process is time-consuming and complex. Moreover, we may not be successful in our efforts to establish a strategic partnership or other alternative arrangement for our product candidates because they may be deemed to be at too early of a stage of development for collaborative effort, and third parties may not view our product candidates as having the requisite potential to demonstrate safety and efficacy. If we license products or acquire businesses, we may not be able to realize the benefit of such transactions if we are unable to successfully integrate them with our existing operations and company culture. Any licensed products or acquired businesses may also subject us to the risk of regulatory enforcement should the product or business not be compliant with applicable regulatory requirements. We cannot be certain that, following a strategic transaction or licensing arrangement, we will achieve the revenue or specific net income that justifies such a transaction.
We rely on CMOs to manufacture our nonclinical and clinical pharmaceutical supplies and expect to continue to rely on CMOs to produce commercial supplies of any approved product candidate, and our dependence on CMOs could adversely impact its business.
We rely on CMOs for the manufacture of nonclinical and clinical supplies of our product candidates and plan to continue to do so for commercial supplies should we receive marketing approval for any of our product candidates.
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This reliance also results in our reduced control over the manufacture of our product candidates and the protection of our trade secrets and know-how from misappropriation or inadvertent disclosure, which may adversely affect our future business prospects. Nevertheless, as the developer of the product candidates and sponsor of clinical trials involving such product candidates, we continue to have regulatory obligations to maintain oversight of the CMOs to ensure compliance with, among other things, contractual obligations, specifications, and current good manufacturing practices (“cGMP”).
In complying with the manufacturing regulations of the FDA and other comparable foreign regulatory authorities, we and our third-party suppliers must spend significant time, money and effort in the areas of design and development, testing, including but not limited to, several complex release tests, including tests for biological potency, production, record-keeping and quality control to assure that the products meet applicable specifications and other regulatory requirements. Although our agreements with our CMOs require them to perform according to certain cGMP, such as those relating to quality control, quality assurance and qualified personnel, we cannot control the conduct of our CMOs to implement and maintain these standards. If our CMOs do not successfully carry out their contractual duties, meet expected deadlines or manufacture our product candidates in accordance with regulatory requirements, if there are disagreements between us and such parties, or if such parties are unable to support the commercialization of any of our product candidates for which we obtain marketing approval, we may not be able to produce, or may be delayed in producing sufficient product to meet our supply requirements. Any delays in obtaining adequate supplies on adequate terms with respect to our product candidates and components, due to manufacturing issues, global trade policies, or for other reasons, may delay the development, approval, or commercialization of our product candidates.
We may not succeed in our efforts to establish manufacturing relationships on commercially reasonable terms. Our product candidates may compete with other products and product candidates for access to manufacturing facilities, of which there are a limited number that operate under cGMP conditions and that are both capable of manufacturing our product candidates and willing to do so. Even if we do establish such collaborations or arrangements, our CMOs may breach, terminate, or not renew these agreements. These facilities may also be affected by general economic conditions, including but not limited to political unrest, global trade wars, natural disasters, such as floods or fires, acts of war, terrorism, or disease outbreaks, or such facilities could face manufacturing issues, such as contamination or adverse regulatory findings following a regulatory inspection. CMOs may also be subject to power failures and/or other utility failures or experience the breakdown, failure, substandard performance or improper installation or operation of equipment in the manufacturing process. Further, our CMOs may be temporarily unable to manufacture our product candidates due to government restrictions, requirements, or limitations. If our CMOs cease to manufacture our product candidates for any reason, we would experience delays in obtaining sufficient quantities of our product for us to meet commercial demand if we receive marketing approval or in advancing our development programs while we identify and qualify replacement suppliers. We could also incur added costs and delays in identifying and qualifying any such replacements and transferring any necessary technology and processes. The terms of a new arrangement may also be less favorable than any prior arrangements, if we are able to negotiate a new arrangement at all. The addition of a new or alternative CMO may also require FDA approval and may have a material adverse effect on our business.
We or our CMOs may also encounter shortages in the raw materials or substances necessary to produce our product candidates in the quantities and at the quality needed for our nonclinical studies and clinical trials or, if any of our product candidates are approved for commercialization, to produce our products on a commercial scale, meet an increase in demand, or compete effectively. Such shortages may occur for a variety of reasons, including capacity constraints, delays or disruptions in the market, and shortages caused by the purchase of such materials by our competitors or others. Our or our third-party manufacturers’ failure to obtain the raw materials or substances necessary to manufacture sufficient quantities of our product candidates may have a material adverse effect on our business.
Moreover, any problems or delays we experience in preparing for commercial-scale manufacturing of a product candidate or component, including manufacturing validation, may result in a delay in a future marketing approval, if any, or commercial launch of any of our product candidates, should they receive regulatory approval, or may impair our ability to manufacture commercial quantities or manufacture such quantities at an acceptable cost, which could result in the delay, prevention, or impairment of commercialization of our product candidates, if approved, and could adversely affect our business. Furthermore, if the future manufacturers of the commercial supplies of our products, if approved, fail to deliver the required commercial quantities of our product candidates on a timely basis and at commercially reasonable prices, we would likely be unable to meet demand for our products and we could lose potential revenues. The manufacture of biological products requires significant expertise and capital investment, including the development of advanced manufacturing techniques and process controls. Manufacturers of biologics often encounter difficulties in production, particularly in scaling up initial production. These problems include difficulties with production costs and yields, quality control, including stability of the product candidate and quality assurance testing, shortages of qualified personnel, and compliance with strictly enforced federal, state, and foreign regulations. If our manufacturers were to encounter any of these difficulties and were unable to perform as agreed,
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our ability to provide our product candidates for use in nonclinical studies or our current and planned clinical trials, or, if any of our product candidates are approved, our ability to produce our product for commercial use, could be jeopardized.
In addition, all manufacturers of our product candidates used in clinical trials and of our products for commercial supply, should any of our product candidates receive regulatory approval, must comply with cGMP regulations promulgated by the FDA and equivalent foreign regulatory authorities that are applicable to both finished products and their active components used both for clinical and commercial supply. Regulatory authorities enforce these requirements through facility inspections. CMO facilities must be satisfactory to the FDA and equivalent foreign regulatory authorities as determined by inspections that will be conducted after we submit our marketing applications to the appropriate agencies and prior to product approval and commercialization. Our CMOs will also be subject to continuing, periodic regulatory authority inspections should our product candidates receive marketing approval. Further, we, in cooperation with our CMOs, must supply all necessary chemistry, manufacturing, and control documentation to the FDA and equivalent foreign regulatory authorities in support of a marketing application on a timely basis.
The cGMP include quality control, quality assurance, and the maintenance of records and documentation. Manufacturers of our product candidates may be unable to comply with our specifications, cGMP or with other applicable regulatory requirements. Poor control of production processes can lead to the introduction of adventitious agents or other contaminants, or to inadvertent changes in the properties or stability of a product candidate that may not be detectable in final product testing. If our CMOs cannot successfully manufacture material that conforms to our specifications and the applicable regulatory requirements, they may not be able to secure or maintain regulatory acceptance of their manufacturing facilities for the purpose of producing our product candidates.
Deviations from manufacturing requirements may also require reporting and remedial measures that may be costly and/or time-consuming for us or a third party to implement and that may include the temporary or permanent suspension of a clinical trial or commercial sales, if any of our product candidates receives regulatory approval, or the temporary or permanent closure of a facility. Any such remedial measure could materially harm our business. Any delay in obtaining products or product candidates that comply with the applicable regulatory requirements may result in delays to nonclinical studies and clinical trials, or potential product approvals or commercialization. Any such delay may also require that we conduct additional studies.
While we are ultimately responsible for the manufacture and regulatory compliance of our products and product candidates, we have little control over our manufacturers’ compliance with these regulations and standards other than through our contractual arrangements. If the FDA or a comparable foreign regulatory authority does not find these facilities satisfactory for the manufacture of our products, if approved, or product candidates, or if such authorities find such facilities to be noncompliant in the future, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain and maintain regulatory approval for or market our product candidates, if approved. Any new manufacturers would need to either obtain or develop the necessary manufacturing know-how, and obtain the necessary equipment and materials, which may take substantial time and investment. We must also receive FDA or other relevant comparable regulatory authority approval for the use of any new manufacturers for commercial supply.
Our failure, or the failure of our third-party manufacturers, to comply with applicable regulatory requirements may result in regulatory enforcement actions against our manufacturers or us, including fines and civil and criminal penalties, suspension of or restrictions on production, injunctions, delay, withdrawal or denial of product approval or supplements to approved products, clinical holds or termination of clinical studies, warning or untitled letters, regulatory authority communications warning the public about safety issues with a product, refusal to permit the import or export of a product, product seizure, detention, or recall, operating restrictions, civil penalties, criminal prosecution, corporate integrity agreements, or consent decrees and equivalent foreign sanctions. Depending on the severity of any potential regulatory action, supplies of our product candidates or products, if approved, could be interrupted or limited, which could have a material adverse effect on our business.
A portion of the manufacturing for our product candidates takes place in China through third-party manufacturers. A significant disruption in the operation of those manufacturers, a trade war or political unrest in China, or a change in the regulatory framework in the United States or China, could materially adversely affect our business, financial condition and results of operations. The recently proposed BIOSECURE Act is aimed at discouraging federal contracting with certain Chinese biotechnology companies for biotechnology equipment or services and the enactment and implementation of the BIOSECURE Act has the potential to impact supply of our product candidates. Additionally, if following the enactment and implementation of the BIOSECURE ACT we are required to change manufacturers for any reason, we will be required to verify that the new manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations and guidelines. We anticipate that the complexity of the manufacturing process may impact the amount of time it may take to secure a replacement manufacturer and such delays could negatively affect our ability to develop product candidates in a timely manner or within budget, which could materially adversely affect our business, financial condition and results of operations.
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We rely on third parties to conduct some of our nonclinical studies and all of our clinical trials. If these third parties do not meet our deadlines or otherwise conduct the trials as required, our development programs could be delayed or unsuccessful and we may not be able to obtain regulatory approval for or commercialize our product candidates when expected or at all.
We do not have the ability to conduct all aspects of our clinical trials ourselves and do not currently plan to independently conduct clinical trials. We use third parties, such as CROs, to conduct, supervise, and monitor the AMPLIFY-201 and AMPLIFY-7P trials and will rely upon such CROs, as well as medical institutions, investigators and consultants, to conduct these trials and any future clinical trials that we may conduct in accordance with our protocols and applicable laws and regulations. In addition, we occasionally use third parties to conduct our nonclinical studies. Our CROs, investigators and other service providers play a significant role in the conduct of these trials and the subsequent collection and analysis of data from such trials.
Our service providers are not our employees and, except for remedies available to us under our agreements with such third parties, we will have less control over the timing, quality and other aspects of such nonclinical studies and clinical trials than we would have if we were to conduct them on our own. If these third parties do not successfully carry out their contractual duties to us, meet our expected timelines or conduct our nonclinical studies or clinical trials in accordance with regulatory requirements or our stated protocols, if they need to be replaced or if the quality or accuracy of the data they obtain is compromised due to their failure to adhere to our protocols or applicable regulatory requirements or for other reasons, our trials may need to be repeated, extended, delayed, or terminated. Further, we may not be able to obtain, or may be delayed in obtaining, marketing approvals for our product candidates, we may fail or be delayed in our efforts to successfully commercialize our product candidates, if approved. Such failures may also subject us or our third-party service providers to regulatory enforcement actions. As a result, our results of operations and the commercial prospects for our product candidates could be harmed, our costs could increase and our ability to generate revenues could be delayed. To the extent we are unable to successfully identify and manage the performance of service providers in the future, our business may be materially and adversely affected. Our third-party service providers may also have relationships with other entities, some of which may be our competitors, for whom they may also be conducting trials or other therapeutic development activities that could harm our competitive position.
Agreements with third parties conducting or otherwise assisting with our nonclinical studies or clinical trials might terminate for a variety of reasons, including a failure to perform by such parties. If any of our relationships with these third parties terminate, we may not be able to enter into arrangements with suitable alternative providers or do so on commercially reasonable terms. Switching or adding third parties involves additional cost and requires management time and focus. There is also a natural transition period when a new third party commences work. As a result, if we need to enter into alternative arrangements, we may need to delay our product development activities and our business could be adversely affected. Although we carefully manage our relationships with our third parties, there can be no assurance that we will not encounter challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition and prospects, and results of operations.
Our reliance on third parties for development activities will reduce our control over these activities. Nevertheless, we are responsible for ensuring that each of our studies is conducted in accordance with the applicable protocol, legal, regulatory, and scientific standards and our reliance on third parties does not relieve us of our oversight and regulatory responsibilities. For example, we will remain responsible for ensuring that each of our trials is conducted in accordance with the general investigational plan and protocols for that trial. We must also ensure that our nonclinical studies are conducted in accordance with good laboratory practice (“GLP”) requirements, as appropriate. Moreover, the FDA and comparable foreign regulatory authorities require us to comply with established good clinical practice (“GCP”) standards for conducting, recording, and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity, and confidentiality of trial participants are protected. In addition, our clinical trials must be conducted with product candidates that were produced under cGMP conditions. Regulatory authorities enforce these requirements through periodic inspections of trial sponsors, clinical and nonclinical investigators, manufacturers, and trial sites. If we or any of our third-party service providers fail to comply with applicable regulatory requirements, we or they may be subject to enforcement or other legal actions, the data generated in our trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional studies, which may significantly delay our clinical development plans and the regulatory approval process. We cannot assure you that upon inspection by a given regulatory authority, such regulatory authority will determine that we, our third-party service providers, or clinical trial sites is in substantial compliance with the applicable regulatory requirements.
In addition, we will be required to report certain financial interests of our third-party investigators if these relationships exceed certain financial thresholds or meet other criteria. The FDA or comparable foreign regulatory authorities may question the integrity of the data from those clinical trials conducted by investigators who may have conflicts of interest. We are also required to register certain clinical trials and post the results of certain completed
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clinical trials on a government-sponsored database, clinicaltrials.gov, within specified timeframes. Failure to do so can result in enforcement actions and adverse publicity.
We rely on other third parties to store and distribute our product candidates for nonclinical studies and clinical trials that we conduct.
We also rely on other third parties to store and distribute our product candidates for the nonclinical studies and clinical trials that we are conducting or plan to conduct. Any performance failure, or failure to comply with applicable regulations, on the part of our distributors could delay development, the regulatory approval process, or potential commercialization of our product candidates, producing additional losses and depriving us of potential product revenue.
We may incur substantial product liability claims. Productor indemnification claims relating to the clinical testing of our product candidates.
We face an inherent risk of product liability exposure related to the testing of our product candidates in human clinical trials, and claims maycould be brought against us if the use or misuse of one of our collaboratorsproduct candidates causes, or merely appears to have caused, personal injury or death. We will face an even greater risk of product liability if we receive marketing approval for and commercialize any of our product candidates. Product liability claims might be brought against us by participants enrolledconsumers, healthcare providers, pharmaceutical companies or others selling or otherwise coming into contact with our product candidates and approved products, if any. Any such product liability claims may include allegations of defects in our clinical trials, patients, healthcaremanufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict liability or a breach of warranties. Claims could also be asserted under state consumer protection acts. Product liability claims might be brought against us by consumers, health care providers or others using, administering or selling our products. If we cannot
There is a risk that our future product candidates may induce adverse events. Patients with the diseases targeted by our product candidates may already be in severe or advanced stages of disease and have both known and unknown significant preexisting and potentially life-threatening health risks. During the course of treatment, subjects may suffer adverse events, including death, for reasons that may be related to our product candidates. Such events could subject us to costly litigation, require us to pay substantial amounts of money to injured subjects, delay, negatively impact or end our opportunity to receive or maintain regulatory approval to market our products, or require us to suspend or abandon our commercialization efforts. Even in a circumstance in which an adverse event is unrelated to our product candidates, the investigation into the circumstance may be time-consuming or inconclusive. These investigations may delay our regulatory approval process or impact and limit the type of regulatory approvals our product candidates receive or maintain. As a result of these factors, a product liability claim, even if successfully defend ourselvesdefended, could have a material adverse effect on our business, financial condition or results of operations. Any claims against us, regardless of their merit, could severely harm our financial condition, strain our management and other resources or destroy the prospects for commercialization of the product which is the subject of any such claims, we would incur substantial liabilities. Regardless of merit or eventual outcome,claim. For instance, product liability claims may result in:
withdrawalloss of clinical trial participants;revenue from decreased demand for our products and/or product candidates;
terminationimpairment of clinical trial sitesour business reputation or entire trial programs;financial stability;
incurred costs and time of related litigation;
substantial monetary awards to patients or other claimants;
decreased demand for our product candidatesclaimants, and loss of revenues;revenue;
impairment of our business reputation;
diversion of management and scientific resources from our business operations; andattention;
withdrawal of clinical trial participants and potential termination of clinical trial sites or entire clinical programs;
the inability to commercialize our product candidates.candidates;
We have obtained limitedsignificant negative media attention;
decrease in our stock price;
initiation of investigations, and enforcement actions by regulators; and/or
product recalls, withdrawals, revocation of approvals, or labeling, marketing or promotional restrictions.
If we cannot successfully defend ourselves against these claims, we will incur substantial liabilities or be required to limit development or commercialization of our products or product candidates. Although we maintain product liability and clinical trial insurance coverage, forit may be inadequate to cover all liabilities that we may incur. We anticipate that we will need to increase our clinical trials in the United States and in selected other jurisdictions where we are conducting clinical trials. Our insurance coverage may not reimburse us oras we continue clinical development of our product candidates and if we successfully commercialize any medicine. Insurance coverage is increasingly expensive. We may not be sufficient to reimburse us for any expenses or losses we may suffer. Moreover, insurance coverage is becoming increasingly expensive and, in the future, we may not be
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able to maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise.
Risks Related to Our Business, Industry and Future Commercialization
If any product candidate that we successfully develop does not achieve broad market acceptance among physicians, patients, health care payors and the medical community, the revenues that we generate from sales will be limited.
Even if our product candidates receive regulatory approval, they may not gain market acceptance among physicians, patients, health care payors and the medical community. Market acceptance of our products by the medical community, patients, and third-party payors will depend on a number of factors, some of which are beyond its control, including:
the efficacy of our products and the prevalence and severity of any adverse events;
any potential advantages or disadvantages when compared to alternative treatments;
interactions of our products with other medicines patients are taking and any restrictions on the use of our products together with other medications;
the clinical indications for which the products are approved and the approved claims that we may make for the products;
limitations or warnings contained in the product’s FDA-approved labeling, including potential limitations or warnings for such products that may be more restrictive than other competitive products;
changes in the standard of care for the targeted indications for such product candidates, which could reduce the marketing impact of any claims that we could make following approval, if obtained;
the safety, efficacy, and other potential advantages over alternative treatments, such as relative convenience and ease of administration of such products, and the availability of alternative treatments already used or that may later be approved;
cost of treatment versus economic and clinical benefit in relation to alternative treatments or therapies;
the availability of formulary coverage and adequate coverage or reimbursement by third parties, such as insurance companies and other health care payors, and by U.S. and international government health care programs, including Medicaid and Medicare;
the price concessions required by third-party payors and government health care programs to obtain coverage and payment;
the extent and strength of our marketing and distribution of such products;
distribution and use restrictions imposed by the FDA and equivalent foreign regulatory authorities with respect to such products or to which we agree, for instance, as part of a REMS or voluntary risk management plan;
the timing of market introduction of such products, as well as competitive products;
our ability to offer such products for sale at competitive prices;
our ability to offer programs to facilitate market acceptance and insurance coverage from public and private insurance companies, provide patient assistance, and transition patient coverage;
the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;
the extent and strength of our third-party manufacturer and supplier support;
the approval of other new products, including biosimilar products that may be priced at a substantially lower price than we expect to offer our product candidates for, if approved;
adverse publicity about the product or favorable publicity about competitive products;
support from patient advocacy groups;
the success of any efforts to educate the medical community and third-party payors regarding our products, which efforts may require significant resources and may not be successful; and
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If any product candidate is approved but does not achieve an adequate level of acceptance by physicians, hospitals, health care payors and patients, we may not generate sufficient amountsrevenue from these products and may not become or remain profitable.
Our ability to protectnegotiate, secure and maintain third-party coverage and reimbursement for our product candidates may be affected by political, economic and regulatory developments in the United States, the European Union and other jurisdictions. Governments continue to impose cost containment measures, and third-party payors are increasingly challenging prices charged for medicines and examining their cost effectiveness, in addition to their safety and efficacy. These and other similar developments could significantly limit the degree of market acceptance of any drug or biologic candidate of ours that receives marketing approval in the future.
If we are unable to establish sales and marketing capabilities or enter into agreements with third parties to sell and market any product candidates we may develop, we may not be successful in commercializing those product candidates if and when they are approved.
We do not have a sales or marketing infrastructure and we have limited experience in the sale, marketing, or distribution of pharmaceutical products. To achieve commercial success for any approved medicine for which we retain sales and marketing responsibilities, we must either develop a sales and marketing organization or outsource these functions to third parties. In the future, we may choose to build a focused sales, marketing, and commercial support infrastructure to sell, or participate in sales activities with our collaborators for, some of our current and future product candidates if and when they are approved.
There are risks involved with both establishing and managing our own commercial capabilities and entering into arrangements with third parties to perform these services. For example, recruiting and training a sales force or reimbursement specialists is expensive and time-consuming and could delay any product launch. If the commercial launch of a product candidate for which we recruit a sales force and establish marketing and other commercialization capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses. This may be costly, and our investment would be lost if we cannot retain or reposition our commercialization personnel.
Factors that may inhibit our efforts to commercialize product candidates on our own include:
our inability to recruit and retain adequate numbers of effective sales, marketing, reimbursement, customer service, medical affairs, and other support personnel;
the inability of sales personnel to obtain access to physicians to discuss our products;
the inability of reimbursement professionals to negotiate arrangements for formulary access, reimbursement, and other acceptance by payors, and to secure adequate coverage;
reduced realization on government sales from mandatory discounts, rebates and fees, and from price concessions to private health plans and pharmacy benefit managers necessitated by competition for access to managed formularies;
the clinical indications for which the products are approved and the claims that we may make for the products, as well as any limitations on use or warnings;
the costs associated with training sales and marketing personnel on legal and regulatory compliance matters and monitoring their actions, and any liability for sales or marketing personnel who fail to comply with the applicable legal and regulatory requirements;
restricted or closed distribution channels that make it difficult to distribute our products to different segments of the patient population;
the lack of complementary medicines to be offered by sales personnel, which may put us against losses dueat a competitive disadvantage relative to companies with more extensive product liability. Large judgmentslines; and
unforeseen costs and expenses associated with creating an independent commercialization organization.
If we enter into arrangements with third parties to perform sales, marketing, commercial support, and distribution services, our product revenues or the profitability of these product revenues to us may be lower than if we were to market and sell any product we may develop ourselves. In addition, we may not be successful in entering into arrangements with third parties to commercialize our products or may be unable to do so on terms that are favorable to us. We may have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our products effectively. If we do not establish commercialization capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing any products we may develop.
We face significant competition in an environment of rapid technological change, and there is a possibility that our competitors may achieve regulatory approval before us or develop therapies that are safer or more
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advanced or effective than ours, which may harm our financial condition and our ability to successfully market or commercialize any product candidates we may develop.
The development and commercialization of new therapeutic biologics is highly competitive. Moreover, the immunotherapy field is characterized by rapidly changing technologies, significant competition, and a strong emphasis on intellectual property. We will likely face competition with respect to any product candidates that we may seek to develop or commercialize in the future from numerous pharmaceutical and biotechnology organizations, as well as from academic institutions, government agencies and other public and private research organizations for our current and future product candidates. Our commercial success may be reduced or eliminated and our business, financial condition, results of operations, and prospects may be harmed if our competitors develop products that are safer, more effective or less costly than ours.
A number of well-resourced pharmaceutical and biotechnology companies with established relationships with patient organizations are developing products to inhibit RAS mutated cancers. These products, as well as marketing campaigns by competitors and clinical trial results with competitive products, could significantly diminish our ability to market and sell ELI-002 for RAS mutated cancers, if approved. For example, Amgen Inc. (“Amgen”), Mirati Therapeutics, Inc. (“Mirati”), a wholly owned subsidiary of Bristol Myers Squibb Co., and Revolution Medicines, Inc., among others, have developed small molecule therapies for the treatment of KRAS mutated cancer including G12C and other alleles. Other companies in the immunotherapy and cancer vaccine sector include BioNTech SE, Gilead Sciences Inc., Novartis International AG, Gritstone Oncology, Inc. (“Gritstone”), Hookipa Pharma Inc., Circio Holding ASA, Moderna, Inc. (“Moderna”), Roche Holding Ltd./Genentech, Inc., Merck & Co., Inc. (“Merck”), Bristol Myers Squibb Co., and AstraZeneca Plc. Closest in mechanism to ELI-002 is the Moderna mRNA-5671 cancer vaccine, which is currently in Phase 1 clinical development. While many of these programs are in preclinical stages or Phase 1 clinical trials, Amgen and Mirati have products that are approved by the FDA for the treatment of adult patients with KRAS G12C mutated locally advanced or metastatic non-small cell lung cancer (“NSCLC”), who have received at least one prior systemic therapy. Additionally, Gritstone has product candidates in Phase 2 trials, including an “off the shelf” vaccine for solid tumors. Moderna and Merck are in a combined Phase 3 trial of their personalized cancer vaccine targeting melanoma (mRNA-4157) and BioNTech and Roche are in a combined Phase 2 trial of their personalized cancer vaccine targeting pancreatic cancer (BNT122, RO7198457). Although ELI-002 is being evaluated as an earlier line of therapy (before metastatic disease can be observed on radiographs), it may compete with existing and new therapies that may be approved in the future.
Many of our current or potential competitors, either alone or with their collaboration partners, may have significantly greater financial resources and expertise in research and development, manufacturing, nonclinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize product candidates that are safer, more effective, have fewer or less severe side effects, are more convenient, or are less expensive than the product candidates we may develop or that would render any of our product candidates obsolete or non-competitive. Our competitors also may obtain FDA or other regulatory approval for their product candidates more rapidly than we may obtain approval for our product candidates, which could result in our competitors establishing a strong market position before we are able to enter the market.
Our commercial opportunity may also be reduced or limited if our or our partners are unable to scale up the manufacture of our product candidates to meet clinical or commercial requirements. ELI-002 is comprised of eight active pharmaceutical ingredients (“APIs”), with peptides and nucleotides with a lipid modification. The compositions we seek to develop may exhibit poor pharmaceutical properties, and formulation, purification and stable storage could be challenging.
In addition, we could face litigation with respect to the validity and/or scope of patents relating to our competitors’ products. The availability of competitive products could limit the demand and the price we are able to charge for our products. Further, intellectual property protection for the amphiphile components of our product candidates is dynamic and rapidly evolving. The scope of intellectual property protection for our AMP platform may be limited, and its commercial opportunity may be reduced or limited if our competitors are able to acquire or develop the same or similar technologies.
Corporate and academic collaborators may take actions to delay, prevent, or undermine the success of our products.
Our operating and financial strategy for the development, clinical testing, manufacture, and commercialization of product candidates is heavily dependent on us entering into collaborations with corporations, academic institutions,
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licensors, licensees, and other parties and we may not be successful in establishing such collaborations. Some of our existing collaborations are, and future collaborations may be, terminable at the sole discretion of the collaborator. Replacement collaborators might not be available on attractive terms, or at all. The activities of any collaborator will not be within our control and may not be within our power to influence. Any collaborators may not perform their obligations to our satisfaction, or at all, we may not derive any revenue or profits from such collaborations, and any collaborators may ultimately compete with us. If any collaboration is not pursued, we may require substantially greater capital to undertake development and marketing of our proposed products and may not be able to develop and market such products effectively, if at all. In addition, a lack of development and marketing collaborations may lead to significant delays in introducing proposed products into certain markets and/or reduced sales of proposed products in such markets.
Data provided by collaborators and others upon which we rely that has not been independently verified could turn out to be false, misleading, or incomplete.
We rely on third-party vendors, scientists and collaborators to provide us with significant data and other information related to our projects, clinical trials and our business. If such third parties provide inaccurate, misleading or incomplete data, our business, prospects and results of operations could be materially adversely affected.
Even if we are able to commercialize any product candidates, such products may become subject to unfavorable pricing regulations, reimbursement practices, or health care reform initiatives, which would harm our business.
The regulations that govern pricing and reimbursement for new medicines vary widely from country to country, and current and future legislation may change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. Outside the United States, some countries require approval of the sale price of a medicine before it can be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted. As a result, we might obtain marketing approval for a product candidate in a particular country, but then be subject to price regulations that delay or might even prevent our commercial launch of the product candidate, possibly for lengthy time periods, and negatively impact the revenues we are able to generate from the sale of the product candidate in that country. Adverse pricing limitations may hinder our ability to recoup our investment in one or more product candidates we may develop, even if any such product candidates obtain marketing approval.
Our ability to commercialize any product candidates successfully also will depend in part on the extent to which reimbursement for these product candidates and related treatments will be available from government authorities or health care programs, private health plans, and other organizations. Even if we succeed in bringing one or more products to the market, these products may not be considered medically necessary and/or cost-effective, and the amount reimbursed for any products may be insufficient to allow us to sell our products on a competitive basis. At this time, we are unable to determine their cost effectiveness or the likely level or method of reimbursement for our product candidates. Government authorities and third-party payors, such as private health plans, decide which medications they will pay for and establish reimbursement levels. A primary trend in the U.S. health care industry and elsewhere is cost containment. Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications. Increasingly, third-party payors are challenging the prices charged for medical products and requiring that biopharmaceutical companies provide them with predetermined discounts from list prices. Novel medical products, if covered at all, may be subject to enhanced utilization management controls designed to ensure that the products are used only when medically necessary. Such utilization management controls may discourage the prescription or use of a medical product by increasing the administrative burden associated with its prescription or creating coverage uncertainties for prescribers and patients. We cannot be sure that reimbursement will be available for any product candidate that we commercialize and, if reimbursement is available, that the level of reimbursement will be adequate. Reimbursement may impact the demand for, or the price of, any product candidate for which we obtain marketing approval. If reimbursement is not available or is available only to limited levels, we may not be able to successfully commercialize any product candidate for which we obtain marketing approval.
We currently expect that any drugs we develop may need to be administered under the supervision of a physician on an outpatient basis. Under currently applicable U.S. law, certain therapeutic products that are not usually self-administered (such as most injectable drugs and biologics) may be eligible for coverage under the Medicare Part B program if:
they are incident to a physician’s services;
they are reasonable and necessary for the diagnosis or treatment of the illness or injury for which they are administered according to accepted standards of medical practice; and
they have been awardedapproved by the FDA and meet other requirements of the statute.
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There may be significant delays in class action lawsuitsobtaining reimbursement for newly approved product candidates, and coverage may be more limited than the purposes for which the product candidate is approved by the FDA or other regulatory authorities. Patients who are prescribed medications for the treatment of their conditions, and their prescribing physicians, generally rely on third-party payors to pay all or part of the costs associated with their prescription medications. Patients are unlikely to use our products unless coverage is provided and payment is adequate to cover all or a significant portion of the cost of our products. Therefore, coverage and adequate payment is critical to new product acceptance. Coverage decisions may depend upon clinical and economic standards that disfavor new products when more established or lower cost therapeutic alternatives are already available or subsequently become available. Moreover, eligibility for reimbursement does not imply that any product candidate will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale, and distribution. Interim reimbursement levels for new product candidates, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement rates may vary according to the use of the product candidate and reimbursement in the clinical setting in which it is used may be based on drugsreimbursement levels already set for lower cost therapies or medicines and may be incorporated into existing payments for other services. Net prices for product candidates may be reduced by mandatory discounts or rebates required by government health care programs or private payors and by any future relaxation of laws that presently restrict imports of medicines from countries where they may be sold at lower prices than in the United States. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement rates. However, no uniform policy requirement for coverage and reimbursement for drug products exists among third-party payors in the United States. Therefore, coverage and reimbursement for drug products can differ significantly from payor to payor. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our products to each payor separately, with unanticipated side effects.no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. Our inability to promptly obtain coverage and profitable payment rates from both government-funded and private payors for any approved product candidates we may develop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize medicines, and our overall financial condition.
We believe that the efforts of governments and third-party payors to contain or reduce the cost of health care and legislative and regulatory proposals to broaden the availability of health care will continue to affect the business and financial condition of pharmaceutical and biopharmaceutical companies. A successfulnumber of legislative and regulatory changes in the health care system in the United States and other major health care markets have been proposed and/or adopted in recent years, and such efforts have expanded substantially in recent years.
In particular, in March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Affordability Reconciliation Act (the “ACA”) was signed into law. This legislation changed the system of health care insurance and benefits and was intended to broaden access to health care coverage, enhance remedies against fraud and abuse, add transparency requirements for the health care and health insurance industries, impose taxes and fees on the health care industry, impose health policy reforms, and control costs. This law also contains provisions that would affect companies in the pharmaceutical industry and other health care related industries by imposing additional costs and changes to business practices. Since its enactment, there have been judicial and congressional challenges to certain aspects of the ACA. The uncertainty around the future of the ACA, and in particular the impact to reimbursement levels, may lead to uncertainty or delay in the purchasing decisions of our customers, which may in turn negatively impact our product liability claimsales. We continue to evaluate the effect that the ACA has or seriesany potential changes to the ACA could have on our business. Additional federal and state legislative and regulatory developments are likely, and we expect ongoing initiatives in the United States to increase pressure on drug and biologic pricing and reimbursement. Such reforms could have an adverse effect on anticipated revenues from product candidates that we may successfully develop and for which we may obtain regulatory approval and may affect our overall financial condition and ability to develop product candidates.
If the market opportunities for any of claims brought against us, particularly if judgments exceed our insurance coverage,product candidates are smaller than we believe they are, our potential revenues may be adversely affected, and our business may suffer.
We focus certain research and product development pipelines and our product candidates on lymph node-directed immunotherapies for cancer and infectious diseases. ELI-002 is a KRAS therapeutic vaccine in clinical development for the potential treatment of several cancer types with KRAS mutations. ELI-002 targets six position 12 and one position 13 KRAS mutations, representing approximately 25% of solid tumors.
While we believe that the cancer types to be included in our early-stage clinical trials have a large KRAS mutation positive patient population in the United States, our understanding of both the number of patients who have these diseases, as well as the subset of people with these diseases who have the potential to benefit from treatment with our product candidates, is based on estimates. These estimates may prove to be incorrect and new studies may reduce the estimated incidence or prevalence of these diseases. By example, because some of the cancer indications that we are targeting are rare, certain estimates are based upon studies with small patient populations. Moreover, because our product candidates, such as ELI-002 target specific positions on a mutation, not all patients with the mutation will be treatment candidates. As a result, the number of patients in the United States may turn out
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to be lower than expected, may not be otherwise eligible for treatment with ELI-002, or patients may become increasingly difficult to identify and access for clinical trials, all of which could decrease our cash resources and adversely affect our business, financial condition, results of operations and prospects.
If we or any CMOs and suppliers we engage fail to comply with environmental, health, and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have a material adverse effect on the success of our business.

We and any CMOs and suppliers we engage are subject to numerous federal, state, and local environmental, health, and safety laws, regulations, and permitting requirements, including those governing laboratory procedures; the generation, handling, use, storage, treatment, and disposal of hazardous and regulated materials and wastes; the emission and discharge of hazardous materials into the ground, air, and water; and employee health and safety. Our operations involve the use of hazardous and flammable materials, including chemicals and biological materials. Our operations also produce hazardous waste. We generally contract with third parties for the disposal of these materials and wastes. Although we believe that the safety procedures utilized by us and such third parties for handling and disposing of these materials and wastes generally comply with the standards prescribed by applicable laws and regulations, we cannot guarantee that this is the case or eliminate the risk of accidental contamination or injury from these materials. In the event of contamination or injury resulting from our use of hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. Under certain environmental laws, we could be held responsible for costs relating to any contamination at our current or past facilities and at third-party facilities. We also could incur significant costs associated with civil or criminal fines and penalties.
Compliance with applicable environmental laws and regulations may be expensive, and current or future environmental laws and regulations may impair our research and product development efforts. In addition, we cannot entirely eliminate the risk of accidental injury or contamination from these materials or wastes. Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. We do not carry specific biological or hazardous waste insurance coverage, and our property, casualty, and general liability insurance policies (which provide for adequate and reasonable amounts of coverage for a company in our industry and at our size and stage) specifically exclude coverage for damages and fines arising from biological or hazardous waste exposure or contamination. Accordingly, in the event of contamination or injury, we could be held liable for damages or be penalized with fines in an amount exceeding our resources, and our clinical trials or regulatory approvals could be suspended, which could have a material adverse effect on our business, financial condition, results of operations, and prospects.
In addition, we may incur substantial costs in order to comply with current or future environmental, health, and safety laws, regulations, and permitting requirements. These current or future laws, regulations, and permitting requirements may impair our research, development, or production efforts. Failure to comply with these laws, regulations, and permitting requirements also may result in substantial fines, penalties, or other sanctions or business disruptions, which could have a material adverse effect on our business, financial condition, results of operations, and prospects.
Any CMOs and suppliers we engage will also be subject to these and other environmental, health, and safety laws and regulations. Liabilities they incur pursuant to these laws and regulations could result in significant costs or an interruption in operations, which could have a material adverse effect on our business, financial condition, results of operations, and prospects.
Our technologies are novel, and any product candidates we develop may be complex and difficult to manufacture on a clinical or commercial scale. We could experience delays in satisfying regulatory authorities or production problems that result in delays in our development or commercialization programs, limit the supply of our product candidates we may develop, or otherwise harm our business.
Our AMP platform is novel, and the manufacture of products on the basis of our platform is untested at a large scale. Any current and future product candidates will likely require processing steps that are more complex than those required for most chemical pharmaceuticals. Problems with the manufacturing process, even minor deviations from the normal process, could result in product defects or manufacturing failures that result in lot failures, product recalls, product liability claims, insufficient inventory, or potentially delay progression of our regulatory filings. Even if we successfully develop product candidates, we may encounter problems achieving adequate quantities and quality of clinical-grade materials that meet FDA or other comparable applicable foreign standards or specifications with consistent and acceptable production yields and costs. If we or our CMOs are unable to scale our manufacturing at the same levels of quality and efficiency, we may not be able to supply the required number of doses for our current or planned clinical trials or for commercial supply, if any of our product candidates receive regulatory approval, and our business could be harmed.
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As product candidates proceed through nonclinical studies to clinical trials towards potential approval and commercialization, it is common that various aspects of the development program, such as manufacturing methods and formulation, are tested and then altered along the way in an effort to optimize processes and results. We have updated ELI-002, with two peptides (ELI-002-2P), to a new version of ELI-002, with seven peptides (ELI-002-7P), as part of our product development activities, and, may continue to update ELI-002 in the future if needed and subject to receipt of additional funding. Any such changes could cause any product candidates we may develop to perform differently and affect the results of clinical trials conducted with the materials manufactured using altered processes. Such changes may also require a new IND to be filed, additional testing, FDA notification, and FDA authorization. This could delay completion of clinical trials, require the conduct of bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay approval of our product candidates and jeopardize our ability to commence sales and generate revenue. For instance, the FDA may require that we conduct a comparability study that evaluates the potential differences in the product candidate resulting from the change. Delays in designing and completing such a study to the satisfaction of the FDA could delay or preclude our development and commercialization plans, and the regulatory approval of our product candidates. Any of the foregoing could limit our future revenues and growth. Any changes would also require that we devote time and resources to manufacturing development and would also likely require additional testing and regulatory actions on our part, which may delay the development of our product candidates.
In addition, the FDA and other regulatory authorities may require us to submit samples of any lot of any approved product together with the protocols showing the results of applicable tests at any time. Under some circumstances, a regulatory authority may require that we do not distribute a lot until the agency authorizes its release. Slight deviations in the manufacturing process, including those affecting quality attributes and stability, may result in unacceptable changes in the product that could result in lot failures or product recalls. Lot failures or product recalls could cause us to delay clinical trials or product launches, which could be costly to us and otherwise harm our business, financial condition, results of operations, and prospects.
We also may encounter problems hiring and retaining the experienced scientific, quality control, and manufacturing personnel needed to manage our manufacturing process, which could result in delays in our production or difficulties in maintaining compliance with applicable regulatory requirements.
The manufacture of biopharmaceutical products is complex and requires significant expertise, including the development of advanced manufacturing techniques and process controls. For example, given the aseptic controls required for the manufacture of our product candidates, if contaminants are discovered in our supply of product candidates or in the manufacturing facilities, such manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination. Any such contamination could materially harm our ability to produce product candidates on schedule and could delay our development programs and results of operations and cause reputational damage. We cannot assure that any such issues relating to the manufacture of ELI-002 or any other product candidate will not occur in the future or that significant delays would not occur as a result of any such issue.
ELI-002 drug substances and drug products are supplied by multiple manufacturers at present. Any problems in our manufacturing process or the facilities with which we contract to make, store or ship our product candidates or any problems caused by it, our vendors or other factors not in our control could result in the loss of usable product or prevent or delay the delivery of product candidates to patients in our clinical trials, including the AMPLIFY-201 and the AMPLIFY-7P trials. Any such loss or delay could materially delay our development timelines and harm our business, financial condition and results of operations. Such losses or delays could also make us a less attractive collaborator for potential partners, including larger pharmaceutical companies and academic research institutions, which could limit our access to additional attractive development programs. Problems with third-party manufacturing processes or facilities also could restrict our ability to ensure sufficient clinical material for any clinical trials we may be conducting or plan to conduct and meet market demand for any product candidates we may develop, obtain regulatory approval for, and commercialize.
Our insurance policies are expensive and only protect us only from some business risks, which will leave us exposed to significant uninsured liabilities.
We do not carry insurance for allmost categories of risk that our business may encounter. Someencounter; however, we may not have adequate levels of the policies wecoverage. We currently maintain include property, general liability, employment benefits liability, business automobile, workers'property, workers’ compensation, products liability malicious invasion of our electronic systems, and clinical trials (U.S.directors’ and foreign), and directors' and officers', employment practices and fiduciary liability insurance.officers’ insurance, along with an umbrella policy. We domay not know, however, if we will be able to maintain existing insurance withat current or adequate levels of coverage. Any significant uninsured liability may require us to pay substantial amounts, which would adversely affect our financialcash position and results of operations.

Risks Related to Our Intellectual Property
Under the terms of the government grant fundingOur success will depend upon intellectual property and proprietary technologies, and we have received, the government may compel usbe unable to license to a third party, or suspend, terminate or withhold grant funding.
A significant amount ofprotect our discovery and initial clinical research has been funded principally by United States government grants and contracts. As with all other pharmaceutical research programs supported in part by federal research dollars, conducting research under federal grants required us to grant the U.S. government a nonexclusive, nontransferable, irrevocable, paid-up license for the government to practice or have the invention practiced on its behalf throughout the world. Under certain circumstances, the government can require the grantee to license a third party, or the government may take title and grant a license itself, known as march-in rights, which may occur if the invention is not brought to practical use within a reasonable time, if health or safety issues arise, if public use of the invention is in jeopardy, or if other legal requirements are not satisfied. Although, to our knowledge, the U.S. government has never forced a grantee to license a third party or taken title and granted a license itself,intellectual property.
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these march-in rights are available to the government, and we cannot assure you that the government will not exercise such rights in the future.
Under the terms and conditions of the government grant funding, we are obligated to comply with various reporting requirements and to take certain administrative actions. Material noncompliance with the terms and conditions of the grant funding may result in one or more enforcement actions by the grant agency. These enforcement actions include denying funds for the cost of funded activities, suspending the grant in whole or in part, pending corrective action, and withholding further grant awards. The grant agency may also terminate the grant for cause, or take other legally available remedies.

Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited.
We have incurred substantial losses during our history and do not expect to become profitable in the near future, and we may never achieve profitability. To the extent that we continue to generate taxable losses, unused losses will carry forward to offset a portion of future taxable income, if any, until such unused losses expire, if ever. Under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, if a corporation undergoes an "ownership change," generally defined as a greater than 50 percentage point change (by value) in its equity ownership by certain stockholders over a rolling three-year period, the corporation's ability to use its pre-change net operating loss carryforwards (NOLs) and other pre-change tax attributes (such as research and development tax credits) to offset its post-change income or taxes may be limited. We have not performed an analysis to assess whether an ownership change has occurred. There is also a risk that due to regulatory changes, such as suspensions on the use of NOLs, or other unforeseen reasons, our existing NOLs could expire or otherwise become unavailable to offset future income tax liabilities. Under the TCJA, as modified by the Coronavirus Aid, Relief and Economic Security Act (the CARES Act), the amount of post-2017 NOLs that are permitted to deduct from U.S. federal income taxes for tax years beginning after December 31, 2020 is limited to 80% of our taxable income in such year, where taxable income is determined without regard to the NOL deduction itself. The TCJA, as modified by the CARES Act, generally eliminates the ability to carry back any NOLs to prior taxable years for tax years beginning after December 31, 2020, while allowing post-2017 unused NOLs to be carried forward indefinitely without expiration. Additionally, state NOLs generated in one state cannot be used to offset income generated in another state. For these reasons, even if we attain profitability, we may be unable to use a material portion of our NOLs and other tax attributes.
Any claims relating to improper handling, storage or disposal of hazardous materials used in our business could be costly and delay our research and development efforts.
Our research and development activities involve the controlled use of potentially harmful hazardous materials, including volatile solvents and chemicals causing cancer. Our operations also produce hazardous waste products. We face the risk of contamination or injury from the use, storage, handling or disposal of these materials. We are subject to federal, state and local laws and regulations governing the use, storage, handling and disposal of these materials and specified waste products. The cost of compliance with these laws and regulations could be significant, and current or future environmental regulations may impair our research, development or production efforts. If one of our employees were accidentally injured from the use, storage, handling, or disposal of these materials, the medical costs related to their treatment would be covered by our workers' compensation insurance policy. However, we do not carry specific hazardous waste insurance coverage and our general liability insurance policy specifically excludes coverage for damages and fines arising from hazardous waste exposure or contamination. Accordingly, in the event of contamination or injury, we could be subject to criminal sanctions or fines or be held liable for damages, our operating licenses could be revoked, or we could be required to suspend or modify our operations and our research and development efforts.
Risks Relating to Our Intellectual Property

It is difficult and costly to protect our proprietary rights, and we may not be able to ensure their protection. If our patent position and potential regulatory exclusivity do not adequately protect our product candidates, others could compete against us more directly, which would harm our business, possibly materially.
Our commercial success will depend, in large part, on obtaining and maintaining patent protection and trade secret protection offor our current and future product candidates and their methods of manufactureformulations and use. Ouruses, as well as successfully defending these patents against third-party challenges. If we or our licensors fail to appropriately prosecute and maintain patent protection for our product candidates, our ability to stop third partiesdevelop and commercialize these product candidates may be adversely affected and we may not be able to prevent competitors from making, using and selling offeringcompeting products. This failure to sellproperly protect the intellectual property rights relating to these product candidates could have a material adverse effect on our financial condition and results of operations.
We have sought patent protection in the United States and internationally related to the AMP platform technology as well as the mKRAS and universal adjuvant programs. We have issued patents in Japan, Nigeria, Russia, and Singapore covering clinical product candidates but the patent portfolio owned by us currently largely comprises pending applications. The patent application process is subject to numerous risks and uncertainties, and there can be no assurance that we or importingour partners will be successful in protecting our product candidates by obtaining and defending patents. These risks and uncertainties include the following:
pending patent applications may not result in any patents being issued;
patents that may be issued or in-licensed may be challenged, invalidated, modified, revoked, circumvented, found to be unenforceable, or otherwise may not provide barriers to entry or any competitive advantage;
because of the extensive time required for development, testing and regulatory review of a potential product, it is dependent uponpossible that before a potential product can be commercialized, any related patent may expire, or remain in existence for only a short period following commercialization, reducing or eliminating any advantage of the extentpatent;
our competitors, many of which have substantially greater resources than us or our partners do, and many of which have made significant investments in competing technologies, may seek, or may already have sought or obtained, patents that will limit, interfere with, or eliminate our ability to make, use, and sell our potential products;
others may design around our patent claims to produce competitive technologies, products or uses which fall outside of the scope of our patents or other intellectual property rights;
others may identify prior art or other bases which could render unpatentable our patent applications or invalidate our patents;
there may be significant pressure on the U.S. government and other international governmental bodies to limit the scope of patent protection both inside and outside the United States for disease treatments that prove successful as a matter of public policy regarding worldwide health concerns;
countries other than the United States may have patent laws less favorable to patentees than those upheld by United States courts, allowing foreign competitors a better opportunity to create, develop, and market competing products; and
we may be involved in lawsuits to protect or enforce its patents or the patents of our licensors, which could be expensive, time-consuming and unsuccessful.
In addition to patents, we also rely on trade secrets and proprietary know-how. Although we have rights under validtaken steps to protect our trade secrets and enforceable patentsunpatented know-how, including entering into confidentiality agreements with third parties, and confidential information and inventions agreements with employees, consultants and advisors, third parties may still obtain this information or come upon this same or similar information independently. We may become subject to claims that us or consultants, advisors or independent contractors that we may engage to assist us in developing our product candidates have wrongfully or inadvertently disclosed to us or used trade secrets or other proprietary information of their former employers or their other clients.
We may be forced to litigate to enforce or defend our intellectual property rights, and/or the intellectual property rights of our licensors.
We may be forced to litigate to enforce or defend our intellectual property rights against infringement by competitors, and to protect our trade secrets against unauthorized use. In so doing, we may place our intellectual property at risk of being invalidated, rendered unenforceable, or limited or narrowed in scope such that cover thesewe may no longer be used to adequately prevent the manufacture and sale of competitive products. Further, an adverse result in any litigation or other proceedings before government agencies such as the United States Patent and Trademark Office (“USPTO”), may place pending applications at risk of non-issuance. Further, interference proceedings, derivation proceedings, entitlement proceedings, ex parte reexamination, inter partes reexamination, inter partes review, post-grant review, and opposition proceedings provoked by third parties or brought by the USPTO or any foreign patent authority may be used to challenge the inventorship, ownership, claim scope, or validity of our patent applications. Additionally, because of the substantial amount of discovery required in connection with intellectual
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property litigation, there is a risk that some of our confidential and proprietary information or trade secrets could be compromised by disclosure during this type of litigation. In addition, there could be public announcements of the results of hearings, motions, or other interim proceedings or developments, and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing, or distribution activities. We may not have sufficient financial or other resources to conduct such litigation or proceedings adequately. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources and more mature and developed intellectual property portfolios. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could have a material adverse effect on our ability to compete in the marketplace.
We have rights in some intellectual property that have been discovered through government funded programs and thus are subject to federal regulations such as “march-in” rights, certain reporting requirements, and a preference for U.S. industry.
We have rights in some intellectual property that have been discovered through government funded programs and thus are subject to federal regulations such as “march-in” rights, certain reporting requirements, and a preference for U.S. industry. Compliance with such regulations may limit our exclusive rights, subject us to expenditure of resources with respect to reporting requirements, and limit our ability to contract with non-U.S. manufacturers. Some of the intellectual property rights in-licensed to us have been generated through the use of U.S. government funding and are therefore subject to certain federal regulations. For example, all of the intellectual property rights licensed to us under our license agreement with MIT have been generated using U.S. government funds. As a result, the U.S. government has certain rights to intellectual property embodied in our current or future products pursuant to the Bayh-Dole Act of 1980. These U.S. government rights in certain inventions developed under government-funded programs include a non-exclusive, non-transferable, irrevocable worldwide license to use inventions for any governmental purpose. In addition, the U.S. government has the right to require us to grant exclusive, partially exclusive, or non-exclusive licenses to any of these inventions to a third party if the government determines that: (i) adequate steps have not been taken to commercialize the invention; (ii) government action is necessary to meet public health or safety needs; or (iii) government action is necessary to meet requirements for public use under federal regulations (also referred to as “march-in rights”). The U.S. government also has the right to take title to these inventions if we fail, or the applicable licensor fails, to disclose the invention to the government, elect title, and file an application to register the intellectual property within specified time limits. In addition, the U.S. government may acquire title to these inventions in any country in which a patent positionsapplication is not filed within specified time limits. Intellectual property generated under government funded programs is also subject to certain reporting requirements, compliance with which may require us, or the applicable licensor, to expend substantial resources. In addition, the U.S. government requires that any products embodying the subject invention or produced through the use of biotechnology and pharmaceutical companiesthe subject invention be manufactured substantially in the U.S. This requirement can be highly uncertain and involve complex legal and factual questions. No consistent policy regardingwaived if the breadthowner of claims allowed in pharmaceutical patents has emergedthe intellectual property can show that reasonable but unsuccessful efforts have been made to dategrant licenses on similar terms to potential licensees that would be likely to manufacture substantially in the United States or that, under the circumstances, domestic manufacture is not commercially feasible. This preference for U.S. manufacturing may limit our ability to license the applicable patent rights on an exclusive basis under certain circumstances.
If we enter into future arrangements involving government funding, and we make inventions as a result of such funding, our intellectual property rights to such discoveries may be subject to the applicable provisions of the Bayh-Dole Act. To the extent any of our current or future intellectual property is generated through the use of U.S. government funding, the provisions of the Bayh-Dole Act may similarly apply. Any exercise by the government of certain of its rights could harm our competitive position, business, financial condition, results of operations and prospects.
We are substantially dependent on patents we license from MIT, and if such licensed patent rights lack legal effect or if a dispute arises under such license agreement and our licensed rights are narrowed or this license is terminated, that could cause significant impairment to our ability to develop and commercialize certain of our product candidates.
Our business is substantially dependent upon technology licensed from MIT. Pursuant to our license agreement with MIT, we were granted an exclusive, worldwide license, including the right to sublicense, under patents and patent applications owned by MIT related to the “Amphiphile” technology for the diagnosis, treatment or prevention of diseases. The patent rights licensed from MIT cover products in development by us for all of our current lead programs in tumor indications where mutant KRAS, rearranged anaplastic lymphoma kinase (“ALK”), or expression of human papillomavirus proteins are a driver of disease, as well as programs using CpG as an adjuvant for immune activation. Therefore, our ability to develop and commercialize several of our product candidates, including ELI-002, are substantially dependent on the legal effectiveness of the MIT patent rights licensed under this agreement and continuation of this agreement. MIT has the right to control the preparation, filing and prosecution of
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the patent applications, and to maintain the patents, covering the patent rights we licensed from MIT under this license agreement. Therefore, we cannot be certain that these patents and patent applications will be prosecuted, maintained and enforced in a manner consistent with the best interests of our business. If MIT fails to maintain such patents, or loses rights to those patents or patent applications, the rights we have licensed may be reduced or eliminated and its right to develop and commercialize any of our products that are the subject of such licensed patent rights could be adversely affected, and we may not be able to prevent competitors from making, using or selling competing products. MIT also has the right to control defense of any claims asserting the invalidity of these licensed patent rights and, even if we are permitted to pursue such defense, we cannot ensure the cooperation of MIT. We cannot be certain that MIT will allocate sufficient resources or prioritize their or our enforcement of such patent rights or their defense of such claims to protect our interests in the licensed patent rights. Even if we are not a party to these legal actions, an adverse outcome could harm its business because it might prevent us from continuing to license intellectual property that it may need to operate its business. In addition, although we have the right to control enforcement of the licensed patents, we may be adversely affected or prejudiced by actions or inactions of MIT and their counsel that took place prior to or after us assuming control.
The license agreement with MIT is complex, and certain provisions in this license agreement may be susceptible to multiple interpretations. The resolution of any contract interpretation disagreement that may arise could narrow or eliminate what we believe to be the scope of our rights to the licensed patent rights or increase what we believe to be our financial or other obligations under the license agreement, either of which could have a material adverse effect on our business, financial condition, results of operations and prospects.
If we or our partners are sued for infringing on the intellectual property rights of third parties, it could be costly and time-consuming, and an unfavorable outcome in any such litigation could have a material adverse effect on our business.
Our success also depends upon our ability and the ability of any of our future collaborators to develop, manufacture, market and sell our product candidates without infringing on the proprietary rights of third parties. Numerous U.S. and foreign issued patents and pending patent applications, which are owned by third parties, exist in the fields in which we are developing products, some of which may be directed at claims that overlap with the subject matter of our intellectual property. Because patent applications can take many years to issue, there may be currently pending applications, unknown to us, which may later result in issued patents that our product candidates or proprietary technologies may infringe upon. Similarly, there may be issued patents relevant to our product candidates of which we are not aware.
In addition, third parties may sue us for infringing on their patents. Even if we are successful in defending any claims of infringement, the defense of such claims may be costly and present a time-consuming distraction. In the event of a successful claim of infringement against us, we may be required to:
pay substantial damages;
stop using its technologies and methods;
stop certain research and development efforts;
develop non-infringing products or methods; and/or
obtain one or more licenses from third parties.
If required, we cannot assure you that we will be able to obtain such licenses on acceptable terms, or at all. If we are sued for infringement, we could encounter substantial delays in the development, manufacture and commercialization of our product candidates. Any litigation, whether to enforce our patent rights or to defend against allegations that we infringed on third-party rights, could be costly, time-consuming, and may distract management from other important tasks.
As is commonplace in the biotechnology and pharmaceutical industry, we employ individuals who were previously employed at other biotechnology or pharmaceutical companies, including our competitors or potential competitors. To the extent our employees are involved in research endeavors which are similar to those which they were involved in at their former employers, we may be subject to claims that such employees and/or we have inadvertently or otherwise used or disclosed the alleged trade secrets or other proprietary information of such former employers. Litigation may be necessary to defend against such claims, which could result in substantial costs, be a distraction to management and ultimately have a material adverse effect on us, even if we are successful in defending such claims.
The biotechnology and pharmaceutical industries have experienced substantial litigation and other proceedings concerning intellectual property rights, and third parties may initiate legal proceedings alleging that we are infringing, misappropriating, or otherwise violating their intellectual property rights, the outcome of which could be uncertain and may prevent, delay or otherwise interfere with our product discovery and development efforts.
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Our commercial success depends upon our ability and the ability of our collaborators and licensors to develop, manufacture, market, and sell ELI-002 and other Amphiphile immunotherapies. The biotechnology and pharmaceutical industries are characterized by extensive litigation regarding patents and other intellectual property rights as well as administrative proceedings for challenging patents, including interference, derivation, inter partes review, post grant review, and reexamination proceedings before the USPTO or oppositions and other comparable proceedings in foreign jurisdictions. We may be subject to and may in the future become party to, or threatened with, adversarial proceedings or litigation concerning intellectual property rights with respect to our Amphiphile platform and any product candidates we may develop, including interference proceedings, post-grant review, inter partes review, and derivation proceedings before the USPTO and similar proceedings in foreign jurisdictions such as oppositions before the European Patent Office (“EPO”). Numerous U.S. and foreign issued patents and pending patent applications that are owned by third parties exist in the fields in which we are developing our product candidates and infringement claims may be asserted against us or our partners based on existing patents or patents that may be granted in the future, regardless of their merit.
As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our AMP platform and product candidates may give rise to claims of infringement of the patent rights of others. Moreover, it is not always clear to industry participants, including us, which patents cover various types of therapies, products or their methods of use or manufacture. As with many technology-based products, there may be third-party patent applications that, if issued, may be construed to cover components of our AMP platform and product candidates. There may also be third-party patents of which we are currently unaware with claims to our technologies, compositions, methods of manufacture or methods of use.
Because of the large number of patents issued and patent applications filed in our fields, third parties may allege they have patent rights encompassing our product candidates, technologies or methods. Third parties may assert that we are employing their proprietary technology without authorization and may file patent infringement claims or lawsuits against us, and if we are found to be infringing on any such third-party patents, we may be required to pay damages, cease commercialization of the infringing technology, or obtain a license from such third party, which may not be available on commercially reasonable terms or at all.
Our ability to commercialize our product candidates in the United States and abroad may be adversely affected if we cannot successfully defend infringement claims, or obtain a license on commercially reasonable terms to relevant third-party patents that cover our product candidates. Even if we believe third-party intellectual property claims are without merit, there can be no assurance that a court would find in our favor on questions of infringement, validity, enforceability, or priority. A court of competent jurisdiction could hold that these third-party patents are valid and enforceable and have been infringed upon, which could materially and adversely affect our ability to commercialize ELI-002 or any other product candidates and any other product candidates or technologies covered by the asserted third-party patents. In order to successfully challenge the validity of any such U.S. patent in federal court, we would need to overcome a presumption of validity. As this burden is a high one requiring us to present clear and convincing evidence as to the invalidity of any such U.S. patent claims, there is no assurance that a court of competent jurisdiction would invalidate the claims of any such U.S. patent. If we are found to be infringing on a third party’s intellectual property rights, and it is unsuccessful in demonstrating that any such patents are invalid or unenforceable, we could be required to obtain a license from such third party to continue developing, manufacturing, and marketing ELI-002 or any other product candidates and its technologies. However, we may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were able to obtain such a license, it could be non-exclusive, thereby giving our competitors and other third parties access to the same technologies licensed to it, and it could require us to make substantial licensing and royalty payments. If we are unable to obtain a necessary license to a third-party patent on commercially reasonable terms, we may be unable to commercialize our AMP platform or product candidates or such commercialization efforts may be significantly delayed, which could in turn significantly harm our business. We also could be forced, including by court order, to cease developing, manufacturing, and commercializing the infringing technology or product candidates. In addition, we could be found liable for significant monetary damages, including treble damages and attorneys’ fees, if we are found to have willfully infringed on a patent or other intellectual property right. Claims that we have misappropriated the confidential information or trade secrets of third parties could have a similar material adverse effect on our business, financial condition, results of operations, and prospects.
The defense of third-party claims of infringement, misappropriation, or violation of intellectual property rights often involves substantial litigation expense and could be a substantial diversion of management and employee time and resources from our business. Some third parties may be able to sustain the costs of complex patent litigation more effectively than we can because they have substantially greater resources. In addition, any uncertainties resulting from the initiation and continuation of any litigation could have a material adverse effect on our ability to raise the funds necessary to continue our operations or could otherwise have a material adverse effect on our business, financial condition, results of operations and prospects. There could also be public announcements of the results of hearings, motions, or other interim proceedings or developments, and if securities analysts or investors perceive these results to be negative, this could have a substantial adverse effect on the price of our common stock.
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Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment, and other requirements imposed by government patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.
Periodic maintenance fees, renewal fees, annuity fees, and various other government fees on patents and applications are due to be paid to the USPTO and foreign patent agencies outside of the United States. States over the lifetime of our owned or licensed patents and applications. For our in-licensed patents and patent applications, we generally rely on our licensors to pay these fees due to U.S. and non-U.S. patent agencies; however, we reimburse MIT for these fees as required by our license agreement with MIT. For our owned patent applications, we rely on our outside patent counsel in the United States and foreign countries to monitor these deadlines and to pay these fees when so instructed.
The USPTO and foreign patent agencies require compliance with several procedural, documentary, fee payment, and other similar provisions, such as the requirement to disclose known prior art, during the patent application process. We depend on our licensors to take the necessary action to comply with these requirements with respect to our licensed intellectual property, and for our owned patent applications, we engage counsel and other professionals to help us comply with these requirements. While certain inadvertent lapses can be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which non-compliance can result in a partial or complete loss of patent rights in the relevant jurisdiction. Were a non-compliance event to occur, our competitors might be able to enter the market with similar or identical products or technology, which could have a material adverse effect on its business, financial condition, results of operations, and prospects.
Changes in patent law in the United States and in non-U.S. jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our technologies and product candidates.
As is the case with other biotech and pharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining and enforcing patents in the biopharmaceutical industry involve both technological and legal complexity, and are therefore costly, time-consuming and inherently uncertain.
Changes in either the patent laws or interpretationsinterpretation of the patent laws could increase the uncertainties and costs surrounding the prosecution of patent applications and the enforcement or defense of our issued patents.
In addition, recent U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations. In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the validity and enforceability of patents, once obtained. Depending on future actions by the U.S. Congress, the federal courts, and the USPTO, the laws and regulations governing patents could change in unpredictable ways that could weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future.
Under the Leahy-Smith America Invents Act (“AIA”), the United States adopted a “first-inventor-to-file” system for deciding which party should be granted a patent when two or more patent applications are filed by different parties claiming the same invention. A third party that filed or files a patent application with the USPTO after March 16, 2013 but before we file an application could therefore have been granted a patent covering an invention of ours even if we had made the invention before it was made by the third party. Since patent applications in the United States and most other countries may diminish the value of our intellectual property. Accordingly,are confidential at least 18 months after filing, we cannot predict the breadth of claims that may be issued in relevant jurisdictions from our present or future patent filings, or those we license from third parties, and further cannot predict the extent to which we will be able to enforce such issued claims in jurisdictions important to our business. If any patents we obtain or license are deemed invalid and unenforceable, our ability to commercialize or license our technology could be adversely affected.
It is possible that others have filed, and in the future may file, patent applications covering products and technologies that are similar, identical or competitive to ours, or that are otherwise important to our business. We cannot be certain that we were the first to file any patent filings ownedapplication related to our drug or biologic candidates.
The AIA also provides a process known as inter partes review (“IPR”), which has been used by many third parties to challenge and invalidate patents. The IPR process is not limited to patents filed after the AIA was enacted and would therefore be available to a third party will not have priority overseeking to invalidate any of our U.S. patents, even those issued or filed before March 16, 2013. Because of a lower evidentiary standard in USPTO proceedings compared to the evidentiary standard in U.S. federal court necessary to invalidate a patent applications filed or in-licensed by us, or that we or our licensors will notclaim, a third party could potentially provide evidence in a USPTO proceeding sufficient for the USPTO to hold a claim invalid even though the same evidence would be involvedinsufficient to invalidate the claim if first presented in interference, opposition or invalidity proceedings before United States or foreign patent offices. The costs of defending our patents or enforcing our proprietary rights in post-issuance administrative proceedings and litigation can be substantial anda district court action. Accordingly, a third party may attempt to use the outcome can be uncertain. An adverse determination in any such submission, proceeding or litigation could reduce the scope of, orUSPTO procedures, e.g., an IPR, to invalidate our patent rights, and/or could allow third parties to commercialize our technology or products and compete directly with us, without payment to us. Furthermore,claims that would not have been invalidated if first challenged by the third party filings may issue as patents that are infringed by our manufacture or commercialization of our products. Licenses may not be available to such third party patents, and challenges to their validity or infringementin a district court action.
Patent terms may be expensive and may not succeed. If the breadth or strength of protection provided byinadequate to protect our patents and patent applications is threatened, or if we are perceived or found to infringe intellectual property rights of others, it could dissuade companies from collaborating with us to license, develop or commercialize current or futurecompetitive position on our product candidates and could impede or preclude our ability to commercialize our products.for an adequate amount of time.
Patents have a limited lifespan. The issuanceterms of individual patents depend upon the legal term for patents in the countries in which they are granted. In most countries, including the United States, if all maintenance fees are timely paid, the natural expiration of a patent is not conclusive as togenerally 20 years from its inventorship, scope, validity or enforceability, and our owned and licensed patents may be challengedearliest non-provisional filing date in the courts orapplicable country. However, the actual protection afforded by a patent officesvaries from country to country, and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country and the United Statesvalidity and abroad. We may become involved in opposition, derivation, reexamination, inter partes review, post-grant review or interference proceedings challenging our patent rights or the patent rights of others. Such challenges may result in loss of exclusivity or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, any of which could limit our ability to stop others from using or commercializing similar or identical technology and products, and/or limit the durationenforceability of the patent protection of our technology and products.
The degree of future protection for our proprietary rights is uncertain because legal means afford only limited protection and may not adequately protect our rights or permit us to gain or keep our competitive advantage. For example:
we might not have been the first to make the inventions covered by our pending patent applications or patents;
others may be able to develop a product similar to, or better than, ours in a way that is not covered by the claims of our patents;
we might not have been the first to file patent applications for these inventions;
others may independently develop similar or alternative technologies or duplicate any of our technologies;
any patents that we have or obtain may not provide us with any competitive advantages;
patents have limited term and geographic scope; we may not be able to secure patents that last long enough and are in relevant jurisdictions to effectively limit competition;
we may not develop additional proprietary technologies that are patentable; or
the patents of others may have an adverse effect on our business.
Without patent protection for our compounds, pharmaceutical compositions, or formulations of our product candidates, our ability to stop others from using or selling our product, or other competitive products including our compounds, may be limited.
If the patent applications we hold or have in-licensed with respect to present or future product candidates fail to issue, if their breadth and/or strength of protection is limited or challenged, or if they fail to provide meaningful exclusivity for present or future product candidates, it could dissuade companies from collaborating with us topatent.
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develop futureVarious extensions including patent term extension (“PTE”) and patent term adjustment (“PTA”) may be available, but the lives of such extensions, and the protections they afford, are limited. Although we will likely seek patent term extensions in the U.S. and in one or more foreign jurisdictions where available, we cannot provide any assurances that any such patent term extensions will be granted and, if so, for how long. Even if patents covering our product candidates are obtained, once the patent life has expired, we may be open to competition from competitive products, including biosimilars and threatengenerics. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting our abilityproduct candidates might expire before or shortly after we or our partners commercialize those candidates. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to commercialize future commercial products. Any such outcomeexclude others from commercializing products similar or identical to ours.
If we are unable to protect the confidentiality of our trade secrets, our business and competitive position could have a materially adverse effect on our business.be harmed.
We mayIn addition to seeking patents for or technologies and product candidates, we also rely on trade secretssecret protection, as well as confidentiality agreements, non-disclosure agreements and invention assignment agreements with our employees, consultants and third parties, to protect our technology,know-how and other confidential and proprietary information, especially where we do not believe patent protection is appropriate or feasible.obtainable.
It is our policy to require our employees, corporate collaborators, outside scientific collaborators, CROs, contract manufacturers, consultants, advisors, and other third parties to execute confidentiality agreements upon the commencement of employment or consulting relationships with us. These agreements generally provide that all confidential information concerning our business or financial affairs developed by or made known to an individual or entity during the course of that party’s relationship with us is to be kept confidential and not disclosed to third parties, except in certain specified circumstances. In the case of employees, the agreements provide that all inventions conceived by the individual, and that are related to our current or planned business or research and development or made during normal working hours, on our premises or using our equipment or proprietary information, are our exclusive property. In the case of consultants and other third-party service providers, the agreements provide us with certain rights to all inventions arising from the services provided to us by those individuals or entities. However, trade secrets are difficultwe cannot guarantee that we have entered into such agreements with each party that may have or have had access to protect. Although we use reasonable efforts to protect our trade secrets or proprietary technologies and processes. Additionally, the assignment of intellectual property rights may not be self-executing, or assignment agreements may be breached, and we may be forced to bring claims against third parties, or defend claims that they may bring against it, to determine the ownership of what we regard as our employees, consultants, contractors, outside scientific collaborators, and other advisorsintellectual property. We may unintentionally or willfully disclose our informationnot be able to competitors. Enforcingobtain adequate remedies for any breaches of such agreements. Ultimately, enforcing a claim that a third party illegally obtained and is using any of ourdisclosed or misappropriated a trade secrets issecret can be difficult, expensive, and time consuming,time-consuming, and the outcome is unpredictable.
In addition to contractual measures, we try to protect the confidential nature of our proprietary information through other appropriate precautions, such as physical and technological security measures. However, trade secrets and know-how can be difficult to protect. These measures may not, for example, in the case of misappropriation of a trade secret by an employee or third party with authorized access, provide adequate protection for our proprietary information. Our security measures may not prevent an employee or consultant from misappropriating our trade secrets and providing them to a competitor, and any recourse we might take against this type of misconduct may not provide an adequate remedy to protect our interests fully. In addition, our trade secrets may be independently developed by others in a manner that could prevent us from receiving legal recourse. If any of our confidential or proprietary information, such as our trade secrets, were to be disclosed or misappropriated, or if any of that information was independently developed by a competitor, our competitive position could be harmed.
In addition, courts inside and outside the United States are sometimes less willing or unwilling to protect trade secrets. Moreover,If we chose to go to court to stop a third party from using any of our trade secrets, we may incur substantial costs. Even if we are successful, these types of lawsuits may consume significant amounts of our time and other resources. Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects.
Third parties may assert that our employees, consultants, or advisors have wrongfully used or disclosed confidential information or misappropriated trade secrets.
As is common in the biotechnology and pharmaceutical industries, we employ individuals that are currently or were previously employed at universities, research institutions or other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Although we try to ensure that our employees, consultants, and advisors do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or these individuals have inadvertently or otherwise used or disclosed intellectual property, including trade secrets or other proprietary information, of any such individual’s current or former employer. We may then be involved in litigation proceedings to defend against these claims. If we fail in defending against any such claims, in addition to potentially paying monetary damages, we may lose valuable intellectual property rights or personnel. Even if we are successful in defending against such claims, litigation could result in substantial costs and distract
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our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments, and, if securities analysts or investors perceive these results to be negative, that perception could have a substantial adverse effect on the price of our common stock. Ultimately, any such litigation could substantially increase our operating losses and reduce our resources available for development activities, and we may not have sufficient financial or other resources to adequately engage in such litigation. For example, some of our competitors may independently develop equivalent knowledge, methods and know-how.

If we do not obtain protection underbe able to sustain the Hatch-Waxman Act and similar legislation outsidecosts of the United States by extending the patent terms and obtaining data exclusivity for our product candidates, our business may be materially harmed.
Depending upon the timing, duration and specifics of FDA marketing approval of our product candidates, if any, one orsuch litigation more of our United States patents may be eligible for limited patent term restoration under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Act. The Hatch-Waxman Act permits a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process.
However, we may not be granted an extension of patent term because, for example, of failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. Moreover, the applicable time period or the scope of patent protection afforded could be lesseffectively than we request. If we are unablecan because of their substantially greater financial resources. In any case, uncertainties resulting from the initiation and continuation of intellectual property litigation or other intellectual property related proceedings could adversely affect our ability to obtain patent term extension orcompete in the term of any such extension is less than what we request, the period during which we will have the right to exclusively market our product will be shortened and our competitors may obtain approval of competing products following our patent expiration, and our revenue could be reduced, possibly materially.marketplace.
Any trademarks we may obtain may be infringed or successfully challenged, resulting in harm to our business.
We expect to rely on trademarks as one means to distinguish any of our product candidates that are approved for marketing from the products of our competitors. We have not yet selectedHowever, our trademarks for our product candidates, and have not yet begun the process of applyingor trade names may be challenged, infringed, circumvented or declared generic or determined to register trademarks for our product candidates. Once we select trademarks and apply to register them, our trademark applicationsbe infringing on other marks. We may not be approved. Thirdable to protect our rights to these trademarks and trade names, which we need to build name recognition among potential partners or customers in our markets of interest. At times, competitors or other third parties may opposeadopt trade names or trademarks similar to ours, thereby impeding our ability to build brand identity and possibly leading to market confusion. In addition, there could be potential trade name or trademark applicationsinfringement claims brought by owners of other registered trademarks or otherwise challengetrademarks that incorporate variations of our use ofregistered or unregistered trademarks or trade names. Over the trademarks. In the event thatlong term, if we are unable to establish name recognition based on our trademarks are successfully challenged,and trade names, then we couldmay not be forcedable to rebrandcompete effectively and our products, whichbusiness may be adversely affected. Our efforts to enforce or protect our proprietary rights related to trademarks, trade secrets, domain names, copyrights or other intellectual property may be ineffective and could result in losssubstantial costs and diversions of brand recognitionresources and could require us to devote resources to advertisingadversely affect our business, financial condition, results of operations and marketing new brands. Our competitors may infringe our trademarks, and we may not have adequate resources to enforce our trademarks.growth prospects.
In addition, any proprietary name we propose to use with ourany product candidate in the United States must be approved by the FDA, regardless of whether we have registered it, or applied to register it, as a trademark. The FDA typically conducts a review of proposed product names, including an evaluation of the potential for confusion with other product names. If the FDA objects to any of our proposed proprietary product names, we may be required to expend significant additional resources in an effort to identify a suitable proprietary product name that would qualify under applicable trademark laws, not infringe the existing rights of third parties, and be acceptable to the FDA.

Intellectual property rights do not necessarily address all potential threats.
Changes in U.S. patent law or the patent lawThe degree of other countries or jurisdictions could diminish the value of patents in general, thereby impairingfuture protection afforded by our ability tointellectual property rights is uncertain because intellectual property rights have limitations and may not adequately protect our products.business or permit us to maintain our competitive advantage. For example:
The United States has enactedany of our current and implemented wide-ranging patent reform legislation. The U.S. Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protectionfuture product candidates, if approved, may eventually become commercially available in certain circumstancesgeneric or weakeningbiosimilar product forms;
others may be able to make immunotherapies that are similar to any of our current and future product candidates or utilize lymph node targeting technology but that are not covered by the rightsclaims of the patents that we license or may own in the future;
we, or our licensors or current or future collaborators, might not have been the first to make the inventions covered by the issued patent owners in certain situations. In addition to increasing uncertainty with regard to our ability to obtain patentsor pending patent application that we license or may own in the future, this combinationpotentially resulting in the invalidation of events has created uncertainty with respectsuch patents or refusal of such applications;
we, or our licensors or current or future collaborators, might not have been the first to file patent applications covering certain of our or their inventions;
we, or our licensors or current or future collaborators, may fail to meet our obligations to the valueU.S. government regarding any in-licensed patents and patent applications funded by U.S. government grants, leading to the loss or unenforceability of patents, once obtained. Dependingpatent rights;
others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing on actions by the U.S. Congress, the Federal Courts and the USPTO, the laws and regulations governing patents could change in unpredictable waysour owned or licensed intellectual property rights;
it is possible that could weaken our ability to obtain new patentspending, owned or to enforce patentslicensed patent applications or those that we have obtained or licensed, or that we might obtainmay own or license in the future. Similarly, changesfuture will not lead to issued patents;
it is possible that there are prior public disclosures that could invalidate our owned or in-licensed patents, or parts of our owned or in-licensed patents;
it is possible that there are unpublished applications or patent applications maintained in patent law and regulations in other countriessecrecy that may later issue with claims covering our product candidates or technology similar to ours;
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jurisdictionsit is possible that our owned or changesin-licensed patents or patent applications omit individual(s) that should be listed as inventor(s) or include individual(s) that should not be listed as inventor(s), which may cause these patents or patents issuing from these patent applications to be held invalid or unenforceable;
issued patents that we hold rights to may be held invalid, unenforceable, or narrowed in scope, including as a result of legal challenges by our competitors;
the claims of our owned or in-licensed issued patents or patent applications, if and when issued, may not cover our product candidates;
the laws of foreign countries may not protect our proprietary rights or the proprietary rights of our licensors or current or future collaborators to the same extent as the laws of the United States;
the inventors of our owned or in-licensed patents or patent applications may become involved with competitors, develop products or processes that design around our patents, or become hostile to us or the patents or patent applications on which they are named as inventors;
our competitors might conduct research and development activities in countries where it does not have patent rights and then use the information learned from such activities to develop competitive products for sale in its major commercial markets;
we have engaged in scientific collaborations in the governmental bodiespast and we intend to continue to do so in the future, and our collaborators may develop adjacent or competing products that enforce themare outside the scope of our patents;
we may not develop additional proprietary technologies that are patentable;
any product candidates we develop may be covered by third-party patents or changesother exclusive rights;
the patents of others may prohibit or otherwise harm our business; or
we may choose not to file a patent in howorder to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
Should any of these events occur, they could have a material adverse effect on our business, financial condition, results of operations, and prospects.
Risks Related to Regulatory and Compliance Matters
The FDA regulatory approval process is lengthy, time-consuming, and inherently unpredictable, and we may experience significant delays in the relevant governmental authority enforces patent lawsclinical development and regulatory approval, if any, of our product candidates.
The research, testing, manufacturing, labeling, approval, selling, import, export, adverse event reporting, record keeping, advertising, promotion, and distribution of drug products, including biologics, are subject to extensive regulation by the FDA and other regulatory authorities in the United States. We are not permitted to market any biological product in the United States until we receive a biologics license from the FDA. We have not previously submitted a BLA to the FDA, or regulationssimilar approval filings to comparable foreign authorities. A BLA must include extensive nonclinical and clinical data and supporting information to establish that the product candidate is safe, pure, potent, and effective for each desired indication. The BLA must also include significant information regarding the chemistry, manufacturing, and controls for the product, and the manufacturing facilities must complete a successful pre-license inspection. The FDA may weakenalso require a panel of experts, referred to as an Advisory Committee, to deliberate on the adequacy of the safety and efficacy data to support licensure. The opinion of the Advisory Committee, although not binding, may have a significant impact on our ability to obtain new patentslicensure of the product candidates based on the completed clinical trials. Accordingly, the regulatory approval pathway for our product candidates may be uncertain, complex, expensive, and lengthy, and approval may not be obtained.
Even if we receive regulatory approval of our product candidates, we will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expense and we may be subject to penalties if we fail to comply with regulatory requirements.
If our product candidates are approved, they will be subject to ongoing regulatory requirements for manufacturing, labeling, packaging, storage, advertising, promotion, sampling, record-keeping, conduct of post-marketing studies, and submission of safety, efficacy, and other post-market information, including both federal and state requirements in the United States and requirements of comparable foreign regulatory authorities.
Manufacturers and manufacturers’ facilities must comply with extensive FDA, and comparable foreign regulatory authority, requirements, including ensuring that quality control and manufacturing procedures conform to cGMP regulations. As such, we and our CMOs will be subject to continual review and inspections to assess compliance with cGMP and adherence to commitments made in any BLA, other marketing applications, and previous responses
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to inspection observations. Accordingly, we and others with whom we work must continue to expend time, money, and effort in all areas of regulatory compliance, including manufacturing, production, and quality control.
Any regulatory approvals that we receive for our product candidates may be subject to limitations on the approved indicated uses for which the product may be marketed or to enforce patentsthe conditions of approval, or contain requirements for potentially costly post-marketing testing, including Phase 4 clinical trials, and surveillance to monitor the safety and efficacy of the product candidate. The FDA may also require a REMS program as a condition of approval of our product candidates, which could entail requirements for long-term patient follow-up, a medication guide, physician communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. In addition, if the FDA or a comparable foreign regulatory authority approves our product candidates, we will have to comply with requirements including submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with cGMP and GCP for any clinical trials that we conduct post-approval.
The FDA strictly regulates marketing, labeling, advertising, and promotion of products that are placed on the market. Drugs and biologics may be promoted only for the approved indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have obtainedimproperly promoted off-label uses may be subject to significant liability.
Later discovery of previously unknown problems with our product candidates, including adverse events of unanticipated severity or licensedfrequency, or with our third-party manufacturers or manufacturing processes, or failure to comply with regulatory requirements may result in revisions to the approved labeling to add new safety information; imposition of post-market studies; clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things:
restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;
fines, restitution, disgorgement of profits or revenues, warning letters or other enforcement-related letters or clinical holds on post-approval clinical trials;
refusal of the FDA to approve pending BLAs or supplements to approved BLAs, or suspension or revocation of product approvals or suspension of any ongoing clinical trials;
product seizure or detention, recalls or refusal to permit the import or export of products;
injunctions or the imposition of civil or criminal penalties; and
consent decrees, corporate integrity agreements, debarment, or exclusion from federal health care programs; or mandated modification of promotional materials and labeling and the issuance of corrective information.
The policies of the FDA and of other regulatory authorities may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product candidates. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or abroad. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained and we may not achieve or sustain profitability.
Additional regulatory burdens and other risks and uncertainties in foreign markets may limit our growth.
Our future growth may depend, in part, on our ability to develop and commercialize product candidates in foreign markets for which we may rely on strategic partnership with third parties. We will not be permitted to market or promote any product candidate before we receive regulatory approval from the applicable regulatory authority in a foreign market, and we may never receive such regulatory approval. To obtain or licenseseparate regulatory approval in foreign countries, we generally must comply with numerous and varying regulatory requirements of such countries regarding safety and efficacy and governing, among other things, clinical trials and commercial sales, pricing and distribution of a product candidate, and we cannot predict success in these jurisdictions. In particular, the European Commission issued a proposal in April 2023 for a new Directive and a new Regulation, which will revise and replace the existing general pharmaceutical legislation. If adopted and implemented as currently proposed, these revisions will significantly change several aspects of drug development and approval in the future.

We may incur substantial costs as a resultEU. If we obtain approval of litigation or other proceedings relatingany of our potential future product candidates and ultimately commercialize any such product candidate in foreign markets, we would be subject to patentrisks and otheruncertainties, including the burden of complying with complex and changing foreign regulatory, tax, accounting and legal requirements and the reduced protection of intellectual property rights.rights in some foreign countries.
If we choose to go to court to stop another party from using the inventions claimed in any patents we obtain, that individual or company has the right to ask the court to rule that such patents are invalid or should not be enforced against that third party. These lawsuits are expensive, would consume time and resources and would divert the attention
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In addition, there is a risk the court will decide that such patents areobtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not valid and we do not have the right to stop the other party from using the inventions. There is also a risk that, even if the validity of such patents is upheld, the court will refuse to stop the other party on the grounds that such other party's activities do not infringe our patents. In addition, the United States Supreme Court has recently modified some tests used by the USPTO in granting patents over the past 20 years, which may decrease the likelihoodguarantee that we will be able to obtain patentsor maintain regulatory approval in any other jurisdiction, but a failure or delay in obtaining regulatory approval in one jurisdiction may have a negative effect on the regulatory approval process in others. For example, even if the FDA grants marketing approval of a product candidate, comparable regulatory authorities in foreign jurisdictions must also approve the manufacturing, marketing and promotion of the product candidate in those countries. Approval procedures vary among jurisdictions and can involve requirements and administrative review periods different from those in the United States, including additional nonclinical studies, or clinical trials as trials conducted in one jurisdiction may not be accepted by regulatory authorities in other jurisdictions. In many jurisdictions outside the United States, a product candidate must be approved for reimbursement before it can be approved for sale in that jurisdiction. In some cases, the price that we intend to charge for our products is also subject to approval.
Obtaining foreign regulatory approvals and compliance with foreign regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction of our products in certain countries. If we fail to comply with the regulatory requirements in international markets and/or to receive applicable marketing approvals, our target market will be reduced and our ability to realize the full market potential of our product candidates will be harmed.
Our relationships with health care providers, physicians, and third-party payors will be subject to applicable anti-kickback, fraud and abuse, anti-bribery and other health care laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm, and diminished profits and future earnings.
Physicians, other health care providers and third-party payors will play a primary role in the recommendation and prescription of ELI-002 or any other product candidates for which we obtain marketing approval. Our future arrangements with third-party payors and customers may expose us to broadly applicable fraud and abuse and other health care laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute our product candidates for which we obtain marketing approval. Violations of the fraud and abuse laws are punishable by criminal and civil sanctions, including, in some instances, exclusion from participation in federal and state health care programs, including Medicare and Medicaid. Restrictions under applicable domestic and foreign health care laws and regulations include but are not limited to the following:
the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase order or recommendation of a good or service reimbursable under a federal healthcare program, such as the Medicare and Medicaid programs; a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation;
federal civil and criminal false claims laws and civil monetary penalties laws, including the federal False Claims Act, which impose criminal and civil penalties against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government; actions may be brought by the government or a whistleblower and may include an assertion that a claim for payment by federal health care programs for items and services which results from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act;
the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) which imposes criminal and civil liability for executing a scheme to defraud any health care benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for health care benefits, items or services; similar to the U.S. federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation;
the federal transparency requirements, sometimes referred to as the “Sunshine Act,” enacted as part of the Patient Protection and Affordable Care Act (the “ACA”), which requires, among other things, manufacturers of drugs, devices, biologics and medical supplies that are reimbursed under Medicare, Medicaid, or the Children’s Health Insurance Program to report annually to the Centers for Medicare & Medicaid Services (“CMS”) information related to payments and other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain advanced non-physician health care practitioners (such as physician assistants and nurse practitioners) and teaching hospitals, as well as physician ownership and investment interests, including such ownership and investment interests held by a physician’s immediate family members;
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analogous state and foreign laws and regulations relating to health care fraud and abuse, such as state anti-kickback and false claims laws, that may apply to sales or marketing arrangements and claims involving health care items or services reimbursed by non-governmental third-party payors, including private insurers;
analogous state and foreign laws that require pharmaceutical companies to track, report and disclose to the government and/or the public information related to payments, gifts, and other transfers of value or remuneration to physicians and other health care providers, marketing activities or expenditures, or product pricing or transparency information, or that require pharmaceutical companies to implement compliance programs that meet certain standards or to restrict or limit interactions between pharmaceutical manufacturers and members of the health care industry;
the U.S. federal laws that require pharmaceutical manufacturers to report certain calculated product prices to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement under federal health care programs;
HIPAA, which imposes obligations on certain covered entity health care providers, health plans, and health care clearinghouses as well as their business associates that perform certain services involving the use or disclosure of individually identifiable health information, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information; and
state and foreign laws which govern the privacy and security of health information in certain circumstances, including state security breach notification laws, state health information privacy laws and federal and state consumer protection laws, many of which differ from each other in significant ways or conflict with each other and often are not preempted by HIPAA, thus complicating compliance efforts.
Because of the breadth of these laws and the narrowness of the statutory exceptions and safe harbors available, it is possible that some of our business activities could be subject to challenge under one or more of such laws. In addition, recent health care reform legislation has strengthened these laws. For example, the ACA, among other things, amends the intent requirement of the federal Anti-Kickback and criminal health care fraud statutes. As a result of such amendment, a person or entity no longer needs to have actual knowledge of these statutes or specific intent to violate them in order to have committed a violation. Moreover, the ACA provides that the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act.
Efforts to ensure that our business arrangements with third parties will comply with applicable health care laws and regulations will involve substantial costs. The shifting compliance environment and the need to build and maintain robust and expandable systems to comply with multiple jurisdictions with different compliance or reporting requirements increases the possibility that a health care company may run afoul of one or more of the requirements. If our operations are found to be in violation of any applicable laws or any other government regulations that apply to us, we may be subject to penalties, including criminal and significant civil monetary penalties, damages, fines, individual imprisonment, disgorgement, contractual damages, reputational harm, exclusion from participation in government health care programs, integrity obligations, injunctions, recall or seizure of products, total or partial suspension of production, denial or withdrawal of pre-marketing product approvals, private qui tam actions brought by individual whistleblowers in the name of the government, refusal to allow us to enter into supply contracts, including government contracts, additional reporting requirements and oversight if subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations.
We intend to develop and implement a comprehensive corporate compliance program prior to the commercialization of our product candidates. Although effective compliance programs can mitigate the risk of investigation and prosecution for violations of these laws, these risks cannot be entirely eliminated. Any action against us for an alleged or suspected violation could cause us to incur significant legal expenses and could divert our management’s attention from the operation of our business, even if our defense is successful. In addition, achieving and sustaining compliance with applicable laws and regulations may be costly to us in terms of money, time and resources. Moreover, federal, state or foreign laws or regulations are subject to change, and while we, our collaborators, manufacturers and/or service providers currently may be compliant, that could change due to changes in interpretation, prevailing industry standards or other reasons.
Health care and other reform legislation may increase the likelihooddifficulty and cost for us and any collaborators we may have to obtain marketing approval of challengeand commercialize our product candidates and affect the prices we, or they, may obtain.
All aspects of any patents we obtain or license.

We may infringe theour business, including research and development, manufacturing, marketing, pricing, sales, litigation, and intellectual property rights, are subject to extensive legislation and regulation. Changes in applicable U.S. federal and state laws and agency regulation, as well as foreign laws and regulations, could have a materially
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negative impact on our business. In the United States and in some other jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the health care system that could prevent or delay marketing approval of our product candidates or any of our potential future product candidates, restrict or regulate post-approval activities, or affect our ability to profitably sell any product candidates for which we obtain marketing approval. Increased scrutiny by the U.S. Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post-marketing testing and other requirements. Congress also must reauthorize the FDA’s user fee programs every five years and often makes changes to those programs in addition to policy or procedural changes that may be negotiated between the FDA and industry stakeholders as part of this periodic reauthorization process. Congress most recently reauthorized the user fee programs in September 2022 without any substantive policy changes.
Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in health care systems with the stated goals of containing health care costs, improving quality and/or expanding access. In the United States, the pharmaceutical industry has been a focus of these efforts and has been significantly affected by major legislative initiatives. In March 2010, Congress passed the ACA, which substantially changed the way health care is financed by both the government and private insurers, and significantly impacts the U.S. pharmaceutical industry.
There remain judicial and Congressional challenges to certain aspects of the ACA, and as a result certain sections of the ACA have not been fully implemented or effectively repealed. However, following several years of litigation in the federal courts, in June 2021, the U.S. Supreme Court upheld the ACA when it dismissed a legal challenge to the law’s constitutionality. Further legislative and regulatory changes under the ACA remain possible, although it is unknown what form any such changes or any law would take, and how or whether it may affect the pharmaceutical industry as a whole or our business in the future. We expect that changes or additions to the ACA, the Medicare and Medicaid programs, and changes stemming from other health care reform measures, especially with regard to health care access, financing or other legislation in individual states, could have a material adverse effect on the health care industry in the United States.
In addition, the Drug Supply Chain Security Act (the “DSCSA”) enacted in 2013 imposed obligations on manufacturers of pharmaceutical products related to product tracking and tracing, and in February 2022, FDA released proposed regulations to amend the national standards for licensing of wholesale drug distributors by the states; establish new minimum standards for state licensing third-party logistics providers; and create a federal system for licensure for use in the absence of a State program, each of which is mandated by the DSCSA. As another example, on December 20, 2019, President Trump signed the Further Consolidated Appropriations Act for 2020 into law (P.L. 116-94) that includes a piece of bipartisan legislation called the CREATES Act. The CREATES Act aims to address the concern articulated by both the FDA and others in the industry that some brand manufacturers have improperly restricted the distribution of their products, including by invoking the existence of a REMS for certain products, to deny generic and biosimilar product developers access to samples of brand products. The CREATES Act establishes a private cause of action that permits a generic or biosimilar product developer to sue the brand manufacturer to compel it to furnish the necessary samples on “commercially reasonable, market-based terms.” Whether and how generic and biosimilar product developments will use this new pathway, as well as the likely outcome of any legal challenges to provisions of the CREATES Act, remain highly uncertain and its potential effects on our future commercial products are unknown. Other legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products. We are unsure whether additional legislative changes will be enacted, or whether the current regulations, guidance or interpretations will be changed, or whether such changes will have any impact on our business.
Additionally, there have been heightened governmental scrutiny in the United States of pharmaceutical pricing practices considering the rising cost of prescription drugs and biologics. Such scrutiny has resulted in several recent congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for products. For example, state legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. In December 2020, the U.S. Supreme Court held unanimously that federal law does not preempt the states’ ability to regulate pharmaceutical benefit managers (“PBMs”) and other members of the health care and pharmaceutical supply chain, an important decision that may lead to further and more aggressive efforts by states in this area.
The U.S. Federal Trade Commission (“FTC”) in mid-2022 also launched sweeping investigations into the practices of the PBM industry that could lead to additional federal and state legislative or regulatory proposals targeting such entities’ operations, pharmacy networks, or financial arrangements. Both the U.S. Congress and state legislatures are increasingly scrutinizing the industry and proposing novel regulatory approaches to address various perceived public policy concerns. Significant efforts to change the PBM industry as it currently exists in the United States may
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affect the entire pharmaceutical supply chain and the business of other stakeholders, including biopharmaceutical product developers like us. Further, in September 2023, the FTC issued a policy statement articulating its view that certain “improper” patent listings by drug developers in FDA’s Orange Book represent an unfair trade practice and indicated that industry should be prepared for potential enforcement actions based on its analysis. The FTC followed that action in November 2023 by publicly calling out over 100 “improper” patent listings made by ten large pharmaceutical companies and initiating an FDA administrative process with respect to those patents. It remains to be seen whether the FTC, other governmental agencies, pharmaceutical manufacturers, or other stakeholders continue to prioritize the policy issue of “improper” patent listings and whether significant litigation will develop in this area. Accordingly, regulatory and government interest in biopharmaceutical industry business practices continues to expand and pose a risk of uncertainty.
At the federal level, there have been several recent U.S. Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drugs. In addition, the Department of Health and Human Services (“HHS”) has solicited feedback on various measures intended to lower drug prices and reduce the out-of-pocket costs of drugs and has implemented others under its existing authority. For example, in May 2019, CMS issued a final rule to allow Medicare Advantage plans the option to use step therapy for Part B drugs beginning January 1, 2020. This final rule codified CMS’s policy change that was effective January 1, 2019.
Most recently, in August 2022, President Biden signed into the law the Inflation Reduction Act of 2022 (“IRA”). Among other things, the IRA has multiple provisions that may impact the prices of drug products that are both sold into the Medicare program and throughout the United States. Starting in 2023, a manufacturer of a drug or biological product covered by Medicare Parts B or D must pay a rebate to the federal government if the product’s price increases faster than the rate of inflation. This calculation is made on a drug product by drug product basis and the amount of the rebate owed to the federal government is directly dependent on the volume of a drug product that is paid for by Medicare Parts B or D. Additionally, starting in payment year 2026, CMS will negotiate drug prices annually for a select number of single source Part D drugs without generic or biosimilar competition. CMS will also negotiate drug prices for a select number of Part B drugs starting for payment year 2028. If a drug product is selected by CMS for negotiation, it is expected that the revenue generated from such drug will decrease. CMS has begun to implement these new authorities and entered into the first set of agreements with pharmaceutical manufacturers to conduct price negotiations in October 2023. However, the IRA’s impact on the biopharmaceutical industry in the United States remains uncertain, in part because multiple large pharmaceutical companies and other stakeholders (e.g., the U.S. Chamber of Commerce) have initiated federal lawsuits against CMS arguing the program is unconstitutional for a variety of reasons, among other complaints. Those lawsuits are currently ongoing.
Any additional federal or state health care reform measures could limit the amounts that third-party payers will pay for future health care products and services, and, in turn, could significantly reduce the projected value of certain development projects and reduce our profitability.
Our employees, principal investigators, consultants, and commercial partners may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements and insider trading.
We are exposed to the risk of fraud or other misconduct by our employees, consultants, and commercial partners, and, our principal investigators. Misconduct by these parties could include intentional failures to comply with FDA regulations or the regulations applicable in the European Union and other jurisdictions, provide accurate information to the FDA or other regulatory authorities, comply with health care fraud and abuse laws and regulations in the United States and abroad, report financial information or data accurately, or disclose unauthorized activities to us. In particular, sales, marketing, and business arrangements in the health care industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs, and other business arrangements. Such misconduct also could involve the improper use of information obtained in the course of clinical trials or interactions with the FDA or other regulatory authorities, which could result in regulatory sanctions and cause serious harm to our reputation. It is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from government investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, financial condition, results of operations, and prospects, including the imposition of significant fines or other sanctions.
Laws and regulations governing any international operations we may have in the future may preclude us from developing, manufacturing and selling certain product candidates outside of the United States and require us to develop and implement costly compliance programs.
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We will be subject to numerous laws and regulations in each jurisdiction outside the United States in which we operate in the future. The creation, implementation and maintenance of international business practices compliance programs is costly and such programs are difficult to enforce, particularly where reliance on third parties is required.
The Foreign Corrupt Practices Act (“FCPA”) prohibits any U.S. individual or business from paying, offering, authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business. The FCPA also obligates companies whose securities are listed in the United States to comply with certain accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations. The anti-bribery provisions of the FCPA are enforced primarily by the U.S. Department of Justice. The SEC is involved with enforcement of the books and records provisions of the FCPA.
Similarly, the U.K. Bribery Act 2010 has extra-territorial effect for companies and individuals having a connection with the United Kingdom. The U.K. Bribery Act prohibits inducements both to public officials and private individuals and organizations. Compliance with the FCPA and the U.K. Bribery Act is expensive and difficult, particularly in countries in which corruption is a recognized problem. In addition, the FCPA presents particular challenges in the pharmaceutical industry, because, in many countries, hospitals are operated by the government, and doctors and other hospital employees are considered foreign officials. Certain payments to hospitals in connection with clinical trials and other work have been deemed to be improper payments to government officials and have led to FCPA enforcement actions.
Various laws, regulations and executive orders also restrict the use and dissemination outside of the United States, or the sharing with certain non-U.S. nationals, of information classified for national security purposes, as well as certain products and technical data relating to those products. If we expand our business outside of the United States, we will be required to dedicate additional resources to comply with these laws, and these laws may preclude us from developing, manufacturing, or selling certain products and product candidates outside of the United States, which could limit our growth potential and increase our development costs. The failure to comply with laws governing international business practices may result in substantial penalties, including suspension or debarment from government contracting. Violations of the FCPA can result in significant civil and criminal penalties. Indictment alone under the FCPA can lead to suspension of the right to do business with the U.S. government until the pending claims are resolved. A conviction under the FCPA can result in long-term disqualification as a government contractor. The termination of a government contract or relationship as a result of our failure to satisfy any of our obligations under laws governing international business practices could have a negative impact on our operations and harm our reputation and ability to procure government contracts. The SEC also may suspend or bar issuers from trading securities on U.S. exchanges for violations of the FCPA’s accounting provisions.
We are subject to, and may in the future become subject to, U.S. federal and state, and foreign, stringent privacy laws, information security laws, regulations, policies and contractual obligations related to data privacy and security and changes in such laws, regulations, policies and contractual obligations could adversely affect our business.
We and our current and potential collaborators may be subject to federal, state and foreign data protection laws and regulations (i.e., laws and regulations that address privacy and data security). In the United States, numerous federal and state laws and regulations, including federal health information privacy laws (e.g., HIPAA as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”)), state data breach notification laws, state health information privacy laws and federal and state consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), that govern the collection, use, disclosure and protection of health-related and other personal information could apply to our operations or the operations of our collaborators. In addition, we may obtain health information from third parties (including research institutions from which we obtain clinical trial data) that are subject to privacy and security requirements under HIPAA, as amended by HITECH, or other privacy and data security laws. Depending on the facts and circumstances, we could be subject to criminal penalties if we knowingly obtain, use, or disclose protected health information maintained by a HIPAA-covered entity in a manner that is not authorized or permitted by HIPAA. However, determining whether protected health information has been handled in compliance with applicable privacy standards and our contractual obligations can be complex and may be subject to changing interpretation.
If we are unable to properly protect the privacy and security of protected health information or other personal, sensitive, or confidential information in our possession, we could be found to have breached our contracts. Further, if we fail to comply with applicable privacy laws, including applicable HIPAA privacy and security standards, we could face significant administrative, civil and criminal penalties. Enforcement activity can also result in financial liability and reputational harm, and responses to such enforcement activity can consume significant internal and outside resources. Furthermore, state attorney generals are authorized to bring civil actions seeking either injunctions or damages in response to violations that threaten the privacy of state residents. In addition to the risks
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associated with enforcement activities and potential contractual liabilities, our ongoing efforts to comply with evolving laws and regulations at the federal and state level may be costly and require ongoing modifications to our policies, procedures and systems.
Many state laws govern the privacy and security of personal information and data in specified circumstances, many of which differ from each other in significant ways, are often not pre-empted by HIPAA, and may have a more prohibitive effect than HIPAA, thus complicating compliance efforts. For example, the California Confidentiality of Medical Information Act (“CMIA”) imposes restrictive requirements regulating the use and disclosure of health information and other personally identifiable information. In addition to fines and penalties imposed upon violators, some of these state laws also afford private rights of action to individuals who believe their personal information has been misused. California’s patient privacy laws, for example, provide for penalties of up to $250,000 and permit injured parties to sue for damages. In addition to the CMIA, in 2018, California enacted the California Consumer Privacy Act (“CCPA”) which creates new individual privacy rights for California consumers (as defined in the law) and places increased privacy and security obligations on entities handling personal data of consumers or households. The CCPA requires covered companies to provide new disclosure to consumers about such companies’ data collection, use and sharing practices, provide such consumers new ways to opt-out of certain sales or transfers of personal information, and provide consumers with additional causes of action. While there is currently an exception for protected health information that is subject to HIPAA and clinical trial regulations, as currently written, the CCPA may impact our business activities. In addition, the California Privacy Rights Act (“CPRA”) was recently enacted to strengthen elements of the CCPA and became effective on January 1, 2023. A number of other states have considered similar privacy proposals, with states like Colorado, Connecticut, Delaware, Florida, Indiana, Iowa, Montana, Oregon, Tennessee, Texas, Utah and Virginia enacting their own privacy laws. These privacy laws may impact our business activities and exemplify the vulnerability of our business to the evolving regulatory environment related to personal data.
In the European Union, we may be subject to the General Data Protection Regulation (“GDPR”) which went into effect in May 2018 and which imposes obligations on companies that operate in our industry with respect to the processing of personal data and the cross-border transfer of such data. The GDPR applies to any company established in the European Economic Area (“EEA”) (which includes the European Union Member States plus Iceland, Liechtenstein, and Norway) and to companies established outside the EEA that process personal data in connection with the offering of goods or services to data subjects in the EEA or the monitoring of the behavior of data subjects in the EEA. The GDPR establishes stringent requirements applicable to the processing of personal data, including strict requirements relating to the validity of consent of data subjects, expanded disclosures about how personal data is used, requirements to conduct data protection impact assessments for “high risk” processing, limitations on retention of personal data, special provisions affording greater protection to and requiring additional compliance measures for “special categories of personal data” including health and genetic information of data subjects, mandatory data breach notification (in certain circumstances), “privacy by design” requirements, and direct obligations on service providers acting as processors. The GDPR also prohibits the international transfer of personal data from the EEA to countries outside of the EEA unless made to a country deemed to have adequate data privacy laws by the European Commission or a data transfer mechanism has been put in place. If we or our partners’ or service providers’ privacy or data security measures fail to comply with the GDPR requirements, we may be subject to litigation, regulatory investigations, enforcement notices requiring us to change the way we use personal data and/or fines of up to 20 million Euros or up to 4% of the total worldwide annual turnover of the preceding financial year, whichever is higher, as well as compensation claims by affected individuals, negative publicity, reputational harm and a potential loss of business and goodwill.
The GDPR may also impose additional compliance obligations relating to the transfer of data between us and our affiliates, collaborators, or other business partners. For example, on July 16, 2020, the Court of Justice of the European Union (“CJEU”), issued a landmark opinion in the case Maximilian Schrems vs. Facebook (Case C-311/18), called Schrems II. This decision (a) calls into question commonly relied upon data transfer mechanisms as between the European Union Member States and the United States (such as the Standard Contractual Clauses) and (b) invalidates the European Union-U.S. Privacy Shield on which many companies had relied as an acceptable mechanism for transferring such data from the European Union to the United States.
On July 10, 2023, the European Commission adopted an adequacy decision for a new mechanism for transferring data from the EU to the United States – the EU-US Data Privacy Framework (the “Framework”). The Framework provides EU individuals with several new rights, including the right to obtain access to their data, or obtain correction or deletion of incorrect or unlawfully handled data. The adequacy decision followed the signing of an executive order introducing new binding safeguards to address the points raised in the Schrems II decision. Notably, the new obligations were geared to ensure that data can be accessed by US intelligence agencies only to the extent necessary and proportionate and to establish an independent and impartial redress mechanism to handle complaints from Europeans concerning the collection of their data for national security purposes. The Commission will continually review developments in the US along with its adequacy decision. Adequacy decisions can be adapted or even withdrawn in the event of developments affecting the level of protection in the applicable
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jurisdiction. Future actions of EU data protection authorities are difficult to predict. Some patients or other service providers may respond to these evolving laws and regulations by asking us to make certain privacy or data-related contractual commitments that we are unable or unwilling to make. This could lead to the loss of current or prospective patients or other business relationships.
Relatedly, following the United Kingdom’s withdrawal from the European Union (i.e., Brexit), and the expiry of the Brexit transition period, which ended on December 31, 2020, the European Union GDPR has been implemented in the United Kingdom (as the “UK GDPR”). The UK GDPR sits alongside the UK Data Protection Act 2018 which implements certain derogations in the European Union GDPR into United Kingdom law. Under the UK GDPR, companies not established in the UK but who process personal data in relation to the offering of goods or services to individuals in the UK, or to monitor their behavior will be subject to the UK GDPR – the requirements of which are (at this time) largely aligned with those under the EU GDPR and as such, may lead to similar compliance and operational costs with potential fines of up to £17.5 million or 4% of global turnover.
Inadequate funding for the FDA, the SEC and other government agencies could hinder their ability to hire and retain key leadership and other personnel, prevent our product candidates from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business rely, which could negatively impact our business.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory, and policy changes. Average review times at the agency have fluctuated in recent years as a result. In addition, government funding of the SEC and other government agencies on which our operations may rely, including those that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable. Disruptions at the FDA and other agencies may also slow the time necessary for new drugs and biologic products to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. For example, over the last several years, the U.S. government has shut down several times, including from December 22, 2018 through January 25, 2019, and congressional impasses periodically threaten to cause future government shutdowns. When a shutdown occurs, certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical activities. Moreover, government shutdowns or slowdowns can increase the time needed for an agency to complete its review or make final approvals or other administrative decisions. If a prolonged government shutdown or slowdown occurs, it could significantly affect the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business. Further, in our operations as a public company, future government shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.
Risks Related to Employee and Operations Matters, Managing Growth and Information Technology
Our business, operations and clinical development timelines and plans are subject to risks arising from epidemic or pandemic diseases.
The COVID-19 worldwide pandemic presented substantial public health and economic challenges and affected our employees, patients, physicians and other healthcare providers, communities and business operations, as well as the U.S. and global economies and financial markets. International and U.S. governmental authorities in impacted regions took multiple and diverse actions in an effort to slow the spread of COVID-19 and variants of the virus, including issuing varying forms of “stay-at-home” orders. To date we have not experienced material disruptions in our business operations due to COVID-19. Such measures taken by the governmental authorities to respond to any future epidemic or pandemic disease outbreaks could disrupt the supply chain and the manufacture or shipment of drug substances and finished drug products for clinical products for use in our clinical trials and research and nonclinical studies and, delay, limit or prevent our employees and CROs from continuing research and development activities, impede our clinical trial initiation and recruitment and the ability of patients to continue in clinical trials, including due to measures taken that may limit social interaction or prevent reopening of high-transmission settings, impede testing, monitoring, data collection and analysis and other related activities, any of which could delay our nonclinical studies and clinical trials and increase our development costs, and have a material adverse effect on our business, financial condition and results of operations. Any future epidemic or pandemic disease outbreak could also potentially further affect the business of the FDA, the European Medical Association (EMA) or other regulatory authorities, which could result in delays in meetings related to our planned clinical trials. Any future epidemic disease outbreak may have an adverse impact on global economic conditions which could have an adverse effect on our business and financial condition, including impairing our ability to raise capital when needed.
Our future success depends on our ability to retain our key executives and to attract, retain, and motivate qualified personnel.
We are highly dependent on the principal members of our senior management and scientific teams. Such principal members are employed “at will,” meaning we or they may terminate the employment relationship at any time. The
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loss of the services of any of these persons could impede the achievement of our research, development, and commercialization objectives.
Recruiting and retaining qualified scientific, clinical, manufacturing, business development, general and administrative and sales and marketing personnel will also be critical to our success. We may not be able to attract and retain these personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel. We also experience competition for the hiring of scientific and clinical personnel from universities and research institutions. In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development and commercialization strategy. Our consultants and advisors, including our scientific co-founder, may be employed by employers other than us and may have commitments under consulting or advisory contracts with other entities that may limit their availability to us. In addition, inflation has had, and we expect that it will continue to have, an impact on the costs that it incurs to attract and retain qualified personnel, and may make it more difficult for us to attract and retain such personnel. The inability to recruit, or loss of services of certain executives, key employees, consultants, or advisors, may impede the progress of our research, development, and commercialization objectives and have a material adverse effect on our business, financial condition, results of operations, and prospects.
If we are unable to hire additional qualified personnel, our ability to grow our business may be harmed.
Over time we will need to hire additional qualified personnel with expertise in drug development, product registration, clinical, preclinical and nonclinical research, quality compliance, government regulation, formulation and manufacturing, financial matters and sales and marketing. We compete for qualified individuals with numerous biopharmaceutical companies, universities and other research institutions. There is currently a shortage of highly qualified personnel in our industry, which is likely to continue. As a result, competition for personnel is intense and the turnover rate can be high. Attracting and retaining qualified personnel will be critical to our success. We may not be able to attract and retain personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for individuals with similar skill sets.
In addition, failure to succeed in development and commercialization of our product candidates may make it more challenging to recruit and retain qualified personnel. The inability to recruit and retain qualified personnel may impede the progress of our research, development and commercialization objectives and would negatively impact our ability to succeed in our product development effortsstrategy.
We expect to expand our development, regulatory, and stop usfuture sales and marketing capabilities, and as a result, we may encounter difficulties in managing our growth, which could disrupt our operations.
As of December 31, 2023, we had 32 full-time employees and, in connection with the growth and advancement of our pipeline and becoming a public company, we expect to increase the number of our employees and the scope of our operations, particularly in the areas of product development, regulatory affairs, and sales and marketing. To manage our anticipated future growth, we must continue to implement and improve our managerial, operational, and financial systems, expand our facilities, and continue to recruit and train additional qualified personnel. Due to our limited financial resources and the limited experience of our management team in managing a company with such anticipated growth, we may not be able to effectively manage the expected expansion of our operations or recruit and train additional qualified personnel. Moreover, the expected physical expansion of our operations may lead to significant costs and may divert our management and business development resources. Any inability to manage growth could delay the execution of our business plans or disrupt our operations.
As a growing biotechnology company, we are actively pursuing new platforms and product candidates in many therapeutic areas and across a wide range of diseases. Successfully developing product candidates for and fully understanding the regulatory and manufacturing pathways to all of these therapeutic areas and disease states requires a significant depth of talent, resources and corporate processes in order to allow simultaneous execution across multiple areas. Due to our limited resources, we may not be able to effectively manage this simultaneous execution and the expansion of our operations or recruit and train additional qualified personnel. This may result in weaknesses in our infrastructure, give rise to operational mistakes, legal or regulatory compliance failures, loss of business opportunities, loss of employees and reduced productivity among remaining employees. The physical expansion of our operations may lead to significant costs and may divert financial resources from commercializingother projects, such as the development of our product candidates. If our management is unable to effectively manage our expected development and expansion, our expenses may increase more than expected, our ability to generate or increase the costs of commercializingour revenue could be reduced, and we may not be able to implement our business strategy. Our future financial performance and our ability to compete effectively and commercialize our product candidates.
Our successcandidates, if approved, will depend in part on our ability to operate without infringing the proprietary rightseffectively manage our future development and expansion.
Our internal information technology systems, or those of third parties. We cannot guarantee that our products or product candidates, or their manufacture or use, will not infringe third-party patents. Furthermore, a third party may claim we or our manufacturing or commercializationvendors, collaborators are using inventions covered by the third party's patent rights. It is also possible a third party might allege our products or product candidates, or their manufacture or use, incorporate or rely on trade secrets improperly received from the third party. A third party alleging violations of their intellectual property rights may go to court to stop us from engaging in our normal operations and activities, including making or selling our product candidates. Defense of such claims, regardless of their merit, are costly and could affect our results of operations and divert the attention of managerial and scientific personnel.
There is a risk a court would decide that we or our commercialization collaborators are infringing the third party's intellectual property rights and would order us or our collaborators to stop relevant activities. In that event, we or our commercialization collaborators may not have a viable way to avoid the infringement and may need to halt commercialization of the relevant product. In addition, there is a risk a court will order us or our collaborators to pay the other party damages for having infringed the other party's intellectual property rights. In the future, we may agree to indemnify our commercial collaborators against certain intellectual property infringement claims brought by third parties. The pharmaceutical and biotechnology industries have produced a proliferation of patents, and it is not always clear to industry participants, including us, which patents cover various types of products or methods of use. The coverage of patents is subject to interpretation by the courts, and the interpretation is not always uniform.
If we are sued for patent or other intellectual property (e.g., trade secret, trademark, etc.) infringement, wecontractors or consultants, may fail or suffer cybersecurity incidents, loss of data, and other disruptions, which could incur significant costs, and delaysresult in a material disruption of our product development or commercialization.
For example, in order to prevail in a suit alleging patent infringement, we would need to demonstrate that our products or methods either do not infringe the claims of the relevant patent or that the patent claims are invalid, and we may not be able to do this. Proving invalidity of a patent is difficult. For example, in the United States, proving invalidity requires a showing of clear and convincing evidence to overcome the presumption of validity enjoyed by issued patents. If we are unable to avoid infringing the patent rights of others, we may be required to seek a license, which may not be available, defend an infringement action or challenge the validity of the patents in court. Patent litigation is costly and time consuming.
We cannot be certain others have not filed patent applications or obtained issued patents for technology that we need to use to commercialize our products, at least because:
some patent applications in the United States may be maintained in secrecy until the patents are issued;
patent applications in the United States are typically not published until 18 months after the priority date;programs, compromise sensitive information
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even published patent applicationsrelated to our business or prevent us from accessing critical information, potentially exposing us to liability or otherwise adversely affecting our business.
In the ordinary course of our business, we collect and patents maystore sensitive data, intellectual property, and proprietary business information. This data encompasses a wide variety of business-critical information including research and development information, clinical trial information, personal information, commercial information, and business and financial information. We face risks relative to protecting this critical information, including loss of access, unauthorized access or disclosure, unauthorized modification, and inadequate monitoring of our controls over these risks.
Despite the implementation of security measures, our internal information technology (“IT”) systems and those of our current and any future third-party vendors, collaborators and other contractors or consultants are vulnerable to risks and damages from a variety of sources, including, interruption, failure, damage, cybersecurity incidents, or data theft from computer viruses, computer hackers, malicious code, employee theft or misuse, malware, including ransomware, social engineering (including phishing attacks), denial-of-service attacks, sophisticated nation-state and nation-state-supported actors, unauthorized access, cyber-attacks, phishing schemes, breaches, interruptions due to employee error or malfeasance, damage from natural disasters, terrorism, war and telecommunication, network, and electrical failures. As use of digital technologies has increased, cybersecurity incidents, including deliberate attacks and attempts to gain unauthorized access to IT systems and networks, have increased in frequency and sophistication. These threats pose a risk to the security of our IT systems and networks and the confidentiality, availability, and integrity of our data. There can be difficultno assurance that we will be successful in detecting or impossible to identify ifpreventing cybersecurity incidents, or successfully mitigating their recordseffects.
Any such disruption or security incident could cause interruptions in available databases are incomplete or inaccurate, or areour operations, and result in a language that is not readily amendable to searching in English;disruption of our development programs and
publications in our business operations. For example, the scientific literature often lag behind actual discoveries.
Our most advanced programs are currently in clinical trials. Patent lawsloss of various jurisdictions, including the United States, exempt clinical trial activities,data from future clinical trials could result in delays in our regulatory approval efforts and mostsignificantly increase our costs to recover or all preclinical work, from patent infringement. These exemptions expire when clinical work is completedreproduce the data. If we were to experience a significant cybersecurity incident that impacts our IT systems or data, the costs associated with the investigation, remediation and application for a commercialization license (e.g., a New Drug Application) is submittedpotential notification of the cybersecurity incident to a relevantcounterparties, regulatory authority (e.g., the FDA). Accordingly, we cannot be confident that third parties will not allege patent infringement with respect to our existing products or programs merely because they have not yet done so.
Our competitors may have filed,authorities, and may in the future file, patent applications covering technology like ours. Any such patent application may have priority over our patent applications, which could further require us to obtain rights to issued patents covering such technologies. If another party has filed a United States patent application on inventions similar to ours, we may have to participate in an interference or derivation proceeding declared by the USPTO to determine priority of invention in the United States. The costs of these proceedingsdata subjects could be substantial,material. In addition, our remediation efforts may not be successful. Cybersecurity incidents could also lead to significant business disruption, including transaction errors, supply chain or manufacturing interruptions, processing inefficiencies, data loss or the loss of or damage to intellectual property or other proprietary information. In addition, our remote workforce could increase our cybersecurity risk, create data accessibility concerns, and it is possiblemake us more susceptible to communication disruption.
To the extent that such efforts would be unsuccessful if, unbeknownstany disruption or cybersecurity incident were to us, the other party had independently arrived at the same or similar invention prior to our own invention, resultingresult in a loss of, or damage to, our United States patentor our third-party vendors’, collaborators’ or other contractors’ or consultants’ data or applications, or inappropriate disclosure of confidential, proprietary, or other critical or sensitive information or data, we could incur liability including litigation exposure, penalties and fines, we could become the subject of regulatory actions or investigations, our competitive position with respectcould be harmed and the further development and commercialization of our product candidates could be delayed. For example, any such event that leads to such inventions, and granting such position to the third party, so that we may need to seek a license from such third party to continueunauthorized access, use or disclosure of personal information, including personal information regarding our use of the technologies, which license might not be available, or might impose significant costs.
Other countries have similar laws that permit secrecy of patent applications and may be entitled to priority over our applications in such jurisdictions.
In addition, we may be subject to claims that we are infringing other intellectual property rights, such as trademarks or copyrights, or misappropriating the trade secrets of others, andpatients, to the extent thatwe have such information, or our employees, consultants could harm our reputation, require us to comply with federal and/or contractors use intellectual propertystate data breach notification laws and foreign law equivalents, and potential contractual obligations, and otherwise subject us to liability under laws and regulations that protect the privacy and security of personal information. Despite our implementation of security and other protective measures, sustained or proprietary information owned by others in their work for us, disputes may arise asrepeated IT system failures that interrupt our ability to generate and maintain data could adversely affect our ability to operate our business. Any of the rights in related or resulting know-how and inventions.
We may not have sufficient resources to bring actions alleging intellectual property infringement to a successful conclusion. In addition, if we do not obtain a license, develop or obtain non-infringing technology, fail to defend an infringement action successfully or have infringed patents declared invalid, we may incur substantial monetary damages, encounter significant delays in bringing our product candidates to market and be precluded from manufacturing or selling our product candidates. Furthermore, even if we are successful in proceedings relating to alleged intellectual property infringement or misappropriation, we may incur substantial costs and divert management's time and attention in pursuing these proceedings, which could have a material adverse effect on us.
Some of our competitors may be able to sustain the costs of complex litigation more effectively than we can because they have substantially greater resources. In addition, any uncertainties resulting from the initiation and continuation of any litigationabove could have a material adverse effect on our ability to raise the funds necessary to continue our operations.
Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.
Periodic maintenance fees, renewal fees, annuity fees and various other governmental fees on patents and/or applications will be due to be paid to the USPTO and various governmental patent agencies outside of the United States in several stages over the lifetime of the patents and/or applications. We have systems in place to remind us to pay these fees, and we employ an outside firm and rely on our outside counsel to pay these fees due to the USPTO and non-United States patent agencies. The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. We employ reputable law firms and other professionals to help us comply, and in many cases, an inadvertent lapse can be cured by payment of a late fee or by other means in accordance with the applicable rules. However, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. In such
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an event, our competitors might be able to enter the market and this circumstance could have a material adverse effect on our business.

Risks Relating to Our Common Stock
Our stock price may be volatile and you may not be able to resell shares of our common stock at or above the price you paid.
The trading price of our common stock could be highly volatile and could be subject to wide fluctuations in response to various factors, some of which are beyond our control. These factors include those discussed in this "Risk Factors" section of this report and others such as:
results from, and any delays in, our clinical trials for ANG-3070;
results of clinical trials of our competitors' products;
competition from existing products or new products that may emerge;
announcements by academic, guideline publishers or other third parties challenging the fundamental premises underlying our approach to treating PPKDs like FSGS and IgAN or IPF;
failure or discontinuation of any of our research and development programs;
manufacturing setbacks or delays of or issues with the supply of the materials for ANG-3070;
announcements relating to future licensing, collaboration or development agreements;
sales of our common stock by or announcements relating to our existing collaborators, including Vifor Pharma;
acquisitions and sales of new products, technologies or businesses;
quarterly variations in ourbusiness, financial condition, reputation, competitive advantage, results of operations or those of our future competitors;
changes in earnings estimates or recommendations by securities analysts;
announcements by us or our competitors of new products, significant contracts, commercial relationships, acquisitions or capital commitments;
developments with respect to intellectual property rights;
our commencement of, or involvement in, litigation;
changes in financial estimates or guidance, including our ability to meet our future revenueprospects. While we maintain cyber-liability insurance (covering security and operating profit or loss estimates or guidance;
any major changes in our board of directors or management;
new legislation in the United States or relevant foreign jurisdictions relating to the sale or pricing of pharmaceuticals;
FDA or other U.S. or foreign regulatory actions affecting us or our industry;
product liability claims or other litigation or public concern about the safety of ANG-3070;
market conditions in the pharmaceutical and biotechnology sectors; and
general economic conditions in the United States and abroad.
In addition, the stock markets in general, and the markets for pharmaceutical and biotechnology stocks in particular, have experienced extreme volatility that may have been unrelated to the operating performance of the issuer. These broad market fluctuations may adversely affect the trading price or liquidity of our common stock. In the past, when the market price of a stock has been volatile, holders of that stock have sometimes instituted securities class action litigation against the issuer. If we were to become involved in securities litigation, we could incur substantial costs and resources and the attention of our management could be diverted from the operation of our business.
An active, liquid and orderly market for our common stockprivacy matters), such insurance may not be sustained.
Our common stock is currently listed on the Nasdaq Global Select Market under the symbol “ANGN”. The price for our common stock may vary and an active or liquid market in our common stock may not be sustained. The lack of an active market may impair your abilityadequate to sell your shares at the time you wish to sell them or at a price that you consider reasonable. An inactive market may also impair our ability to raise capital by selling shares and may impair our ability to acquire other businesses, applications, or technologies using our shares as consideration.
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If we sell shares of our common stock in future financings, stockholders may experience immediate dilution and, as a result, our stock price may decline.
We may, from time to time, issue additional shares of common stock at a discount from the current trading price of our common stock, including pursuant to our 2021 Incentive Award Plan and 2021 Employee Stock Purchase Plan. As a result, our stockholders would experience immediate dilution upon the purchase ofcover any shares of our common stock sold at such discount. In addition, as opportunities present themselves, we may enter into financing or similar arrangements in the future, including the issuance of debt securities, preferred stock or common stock. If we issue common stock or securities convertible into common stock, our common stockholders would experience additional dilution and, as a result, our stock price may decline.
We identified material weaknesses in our internal control over financial reporting and we may identify additional material weaknesses in the future that may cause us to fail to meet our reporting obligations or result in material misstatements of our financial statements. If we fail to remediate any material weaknesses or if we otherwise fail to establish and maintain effective control over financial reporting, our ability to accurately and timely report our financial results could be adversely affected.
We have identified control deficiencies in the design and operation of our internal control over financial reporting that constituted material weaknesses. A material weakness is a deficiency, or a combination of deficiencies, in internal control over financial reporting such that there is a reasonable possibility that a material misstatement of our financial statements will not be prevented or detected on a timely basis.
The material weaknesses identified in our internal control over financial reporting related to (i) insufficient resources with knowledge and expertise in U.S. GAAP to properly evaluate certain complex transactions, including debt instruments and equity instruments; and (ii) insufficient financial reporting and close controls to ensure that incurred expenses are accrued at period end and deliverables from third party contractors are reviewed for accuracy. We have taken a number of actions to remediate these material weaknesses, including engaging SEC compliance and technical accounting consultants to assist in evaluating transactions for conformity with U.S. GAAP; hiring additional finance and accounting personnel to augment accounting staff and to provide more resources for complex accounting matters and financial reporting; and strengthening our financial reporting and close relating to incurred expenses by ensuring our data capture procedures are clearly defined and that responsible personnel, including supervisory personnel, have adequate training regarding the process and expectation.
However, we are still in the process of implementing these processes and controls and we cannot assure you that these measures will be sufficient to remediate the material weaknesses that have been identified or prevent future material weaknesses or significant deficiencies from occurring.
If we are unable to successfully remediate the existing material weaknesses in our internal control over financial reporting, or discover additional material weaknesses in the future, the accuracy and timing of our financial reporting, and our stock price, may be adversely affected and we may be unable to maintain compliance with the applicable stock exchange listing requirements.
We are an "emerging growth company" andlosses experienced as a result of the reduced disclosure and governance requirements applicable to emerging growth companies, our common stock may be less attractive to investors.
We are an "emerging growth company," as defined in Jumpstart Our Business Act of 2012, (JOBS Act), and we intend to take advantage of certain exemptions from various reporting requirements that are applicable to other public companies that are not emerging growth companies including, but not limited to, not being required to comply with the auditor attestation requirements of Section 404, reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements, and exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and obtaining stockholder approval of any golden parachute payments not previously approved. In addition, as an "emerging growth company," the JOBS Act allows us to delay adoption of new or revised accounting pronouncements applicable to public companies until such pronouncements are made applicable to private companies. We have elected to use this extended transition period under the JOBS Act. As a result, our financial statements may not be comparable to the financial statements of issuers who are required to comply with the effective dates for new or revised accounting standards that are applicable to public companies, which may make comparison of our financials to those of other public companies more difficult. Even after we no longer qualify as an emerging growth company, we may still qualify as a "smaller reporting company"cybersecurity incident.
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which would allow us to take advantage of many of the same exemptions from disclosure requirements including not being required to comply for a period of time with the auditor attestation requirements of Section 404, and reduced disclosure obligations regarding executive compensation in this report and our periodic reports and proxy statements.
We cannot predict if investors will find our common stock less attractive because we will rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock price may be more volatile. We may take advantage of these reporting exemptions until we are no longer an emerging growth company or smaller reporting company.
We have completed and may in the future complete related party transactions that were not and may not be conducted on an arm's length basis.
We have in the past and continue to be party to certain transactions with certain entities affiliated with Dr. Goldberg, director and Chairman Emeritus on our Board, as well as certain of his immediate family members. For instance, in November 2013, we granted Ohr Cosmetics, LLC (Ohr), an affiliated company, an exclusive worldwide license, with the right to sublicense, under our patent rights covering one of our CYP26 inhibitors, ANG-3522, for the use in treating conditions of the skin or hair. We own, and the family of Dr. Goldberg, owns approximately 2.4% and 80.6%, respectively, of the membership interests in Ohr. Dr. Goldberg's son is the manager of Ohr.
In addition, we rent office and laboratory space in Uniondale, New York from NovaPark LLC (NovaPark), an affiliated company, under a lease that expires on June 20, 2026. The space that we rent is part of an approximately 110,000-square-foot general laboratory and development facility (NovaPark Facility) for biological and chemistry research owned by NovaPark. We own, and Dr. Goldberg, and Rina Kurz, Dr. Goldberg's spouse, own 10%, 45% and 45%, respectively, of the membership interests in NovaPark.
Provisions in our charter documents and under Delaware law could discourage a takeover that stockholders may consider favorable and may lead to entrenchment of management.
Our amended and restated certificate of incorporation and amended and restated bylaws contain provisions that could delay or prevent changes in control or changes in our management without the consent of our board of directors. These provisions include the following:
a classified board of directors with three-year staggered terms, which may delay the ability of stockholders to change the membership of a majority of our board of directors;
no cumulative voting in the election of directors, which limits the ability of minority stockholders to elect director candidates;
the exclusive right of our board of directors to elect a director to fill a vacancy created by the expansion of the board of directors or the resignation, death or removal of a director, which prevents stockholders from being able to fill vacancies on our board of directors;
the ability of our board of directors to authorize the issuance of shares of preferred stock and to determine the price and other terms of those shares, including preferences and voting rights, without stockholder approval, which could be used to significantly dilute the ownership of a hostile acquiror;
the ability of our board of directors to alter our amended and restated bylaws without obtaining stockholder approval;
the required approval of at least 66 2/3% of the shares entitled to vote at an election of directors to adopt, amend or repeal our amended and restated bylaws or repeal the provisions of our amended and restated certificate of incorporation regarding the election and removal of directors;
a prohibition on stockholder action by written consent, which forces stockholder action to be taken at an annual or special meeting of our stockholders;
the requirement that a special meeting of stockholders may be called only by our chief executive officer or president or chairperson of the board of directors or by the board of directors, which may delay the ability of our stockholders to force consideration of a proposal or to take action, including the removal of directors; and
advance notice procedures that stockholders must comply with in order to nominate candidates to our board of directors or to propose matters to be acted upon at a stockholders' meeting, which may discourage or deter a potential acquiror from conducting a solicitation of proxies to elect the acquiror's own slate of directors or otherwise attempting to obtain control of us.
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We are also subject to the anti-takeover provisions contained in Section 203 of the Delaware General Corporation Law. Under Section 203, a corporation may not, in general, engage in a business combination with any holder of 15% or more of its capital stock unless the holder has held the stock for three years or, among other exceptions, the board of directors has approved the transaction. For a description of our capital stock, see "Description of Capital Stock."
Our amended and restated certificate of incorporation and amended and restated bylaws provide for an exclusive forum in the Court of Chancery of the State of Delaware for certain disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.
Our amended and restated certificate of incorporation and amended and restated bylaws provide that the Court of Chancery of the State of Delaware (or, in the event that the Court of Chancery does not have jurisdiction, the federal district court for the District of Delaware or other state courts of the State of Delaware) is the exclusive forum for any derivative action or proceeding brought on our behalf, any action asserting a claim of breach of fiduciary duty, any action asserting a claim against us arising pursuant to the Delaware General Corporation Law, our amended and restated certificate of incorporation or our amended and restated bylaws, or any action asserting a claim against us that is governed by the internal affairs doctrine; provided that, the exclusive forum provision will not apply to suits brought to enforce any liability or duty created by the Exchange Act or any other claim for which the federal courts have exclusive jurisdiction; and provided further that, if and only if the Court of Chancery of the State of Delaware dismisses any such action for lack of subject matter jurisdiction, such action may be brought in another state or federal court sitting in the State of Delaware. Our amended and restated certificate of incorporation and amended and restated bylaws also provide that the federal district courts of the United States of America will be the exclusive forum for the resolution of any complaint asserting a cause of action against us or any of our directors, officers, employees or agents and arising under the Securities Act. Nothing in our amended and restated certificate of incorporation or amended and restated bylaws precludes stockholders that assert claims under the Exchange Act from bringing such claims in state or federal court, subject to applicable law.
We believe these provisions may benefit us by providing increased consistency in the application of Delaware law and federal securities laws by chancellors and judges, as applicable, particularly experienced in resolving corporate disputes, efficient administration of cases on a more expedited schedule relative to other forums and protection against the burdens of multi-forum litigation. This choice of forum provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or any of our directors, officers, other employees or stockholders, which may discourage lawsuits with respect to such claims, although our stockholders will not be deemed to have waived our compliance with federal securities laws and the rules and regulations thereunder. Furthermore, the enforceability of similar choice of forum provisions in other companies’ certificates of incorporation has been challenged in legal proceedings, and it is possible that a court could find these types of provisions to be inapplicable or unenforceable. While the Delaware courts have determined that such choice of forum provisions are facially valid, a stockholder may nevertheless seek to bring a claim in a venue other than those designated in the exclusive-forum provisions, and there can be no assurance that such provisions will be enforced by a court in those other jurisdictions. If a court were to find the choice of forum provision contained in our amended and restated certificate of incorporation and amended and restated bylaws to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could adversely affect our business and financial condition.
General Risk Factors
Unstable market and economic conditions may have serious adverse consequences on our business, financial condition and stock price.
The global credit and financial markets have recently experienced extreme volatility and disruptions, in the past several years, including most recently as a result of the COVID-19 pandemic and the Russian invasion of Ukraine. Such volatility and disruptions have caused and may continue to cause severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates and uncertainty about economic stability. The financial markets and the global economy may also be adversely affected by the current or anticipated impact of military conflict, including the conflicts in the Middle East and between Russia and Ukraine, geopolitical tensions with China, terrorism or other geopolitical events. Sanctions imposed by the United States and other countries in response to such conflicts, including the ones in the Middle East and in Ukraine, may also adversely impact the financial markets and the global economy, and any economic countermeasures by the affected countries or others could exacerbate market and economic instability. There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur. Our general business strategy may be adversely affected by any
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such economic downturn, volatile business environment or continued unpredictable and unstable market conditions. If the current equity and credit markets deteriorate, it may make any necessary debt or equity financing more difficult, more costly and more dilutive. Failure to secure any necessary financing in a timely manner and on
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favorable terms could have a material adverse effect on our growth strategy, financial performance and stock price and could require us to delay, limit, reduce, or abandon clinicalterminate our product development plans.or future commercialization efforts or grant rights to develop and market our product candidates even if we would otherwise prefer to develop and market such product candidates ourselves, or on less favorable terms than we would otherwise choose. In addition, there is a risk that one or more of our current service providers, manufacturers and other partners may not survive an economic downturn, which could directly affect our ability to attain our operatingclinical development goals on schedule and on budget.
OurUncertainty about global economic conditions could result in increased costs related to the manufacture of our product candidates and, if our product candidates are approved and made available for sale, customers may postpone purchases of our product candidates in response to tighter credit, unemployment, negative financial news and/or declines in income or asset values and other macroeconomic factors, which could have a material adverse effect on demand for our product candidates.
Inflation could adversely affect our business could be affected by litigation, government investigations and enforcement actions.results of operations.
We currently operate in a number of jurisdictions in a highly regulated industry and we could be subject to litigation, government investigation and enforcement actions on a variety of mattersWhile inflation in the United States. or foreign jurisdictions,States has been relatively low in recent years, during 2021 and 2022, the economy in the United States encountered a material level of inflation. The impact of COVID-19, geopolitical developments such as the Russia-Ukraine and Middle East conflicts, geopolitical tensions with China, and global supply chain disruptions continue to increase uncertainty in the outlook of near-term and long-term economic activity, including without limitation, intellectual property, regulatory, product liability, environmental, whistleblower, false claims, privacy, anti-kickback, anti-bribery, securities, commercial, employment,whether inflation will continue and how long, and at what rate. Increases in inflation raise our costs for commodities, labor, materials and services and other claimscosts required to grow and legal proceedingsoperate our business, and failure to secure these on reasonable terms may adversely impact our financial condition. Additionally, increases in inflation, along with the uncertainties surrounding COVID-19, geopolitical developments and global supply chain disruptions, have caused, and may in the future cause, global economic uncertainty and uncertainty about the interest rate environment, which may arise from conductingmake it more difficult, costly or dilutive for us to secure additional financing. A failure to adequately respond to these risks could have a material adverse impact on our business. Any determination that ourfinancial condition, results of operations or activitiescash flows.
U.S. federal income tax reform could adversely affect our business and financial condition.
The rules dealing with U.S. federal, state, and local income taxation are not in compliance with existing laws or regulations could resultconstantly under review by persons involved in the imposition of fines, civillegislative process and criminal penalties, equitable remedies, including disgorgement, injunctive relief, and/by the Internal Revenue Service and the U.S. Treasury Department. Changes to tax laws (which changes may have retroactive application) could adversely affect us or other sanctions against us, and remediation of any such findings could have an adverse effect on our business operations.
Legal proceedings, government investigations and enforcement actions can be expensive and time consuming. An adverse outcome resulting from any such proceeding, investigations or enforcement actions could result in significant damages awards, fines, penalties, exclusion from the federal healthcare programs, healthcare debarment, injunctive relief, product recalls, reputational damage and modificationsholders of our business practices,common stock. In recent years, many such changes have been made and changes are likely to continue to occur in the future. For example, on March 27, 2020, former President Trump signed into law the CARES Act which included certain changes in tax law intended to stimulate the U.S. economy in light of the COVID-19 coronavirus outbreak, including temporary beneficial changes to the treatment of net operating losses (“NOLs”), interest deductibility limitations and payroll tax matters. Additionally, on December 22, 2017, former President Trump signed into law the Tax Cuts and Jobs Act of 2017 (“TCJA”), which significantly reformed the Internal Revenue Code. The TCJA included significant changes to corporate and individual taxation, some of which could adversely impact an investment in our common stock. Under the TCJA, in general, NOLs generated in taxable years beginning after December 31, 2017 may offset no more than 80 percent of such year’s taxable income and there is no ability for such NOLs to be carried back to a prior taxable year. The CARES Act modifies the TCJA with respect to the TCJA’s limitation on the deduction of NOLs and provides that NOLs arising in taxable years beginning after December 31, 2017 and before January 1, 2021, may be carried back to each of the five taxable years preceding the tax year of such loss, but NOLs arising in taxable years beginning after December 31, 2020 may not be carried back. In addition, the CARES Act eliminates the limitation on the deduction of NOLs to 80 percent of current year taxable income for taxable years beginning before January 1, 2021. As a result of such limitation, we may be required to pay federal income tax in some future year notwithstanding that we had a net loss for all years in the aggregate. Future changes in tax laws could have a material adverse effect on our business, andcash flow, financial condition or results of operations. We urge investors to consult with their legal and tax advisers regarding the implications of potential changes in tax laws on an investment in our common stock.
Our employees, principal investigators, consultantsThe market price of our common stock is expected to be volatile, and the market price of our common stock may drop.
The market price of our common stock could be subject to significant fluctuations. Market prices for securities of early-stage pharmaceutical, biotechnology and other life sciences companies have historically been particularly volatile. Some of the factors that may cause the market price of our common stock to fluctuate include:
our ability to obtain regulatory approvals for our product candidates, and delays or failures to obtain such approvals;
failure of any of our product candidates, if approved, to achieve commercial success;
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failure by us to maintain our existing third-party license and supply agreements;
failure by us or our licensors to prosecute, maintain, or enforce our intellectual property rights;
changes in laws or regulations applicable to our product candidates;
any inability to obtain adequate supply of our product candidates or the inability to do so at acceptable prices;
adverse regulatory authority decisions;
adverse results, clinical holds, or delays in the clinical trials of our product candidates or any future clinical trials we may conduct, or changes in the development status of our product candidates;
introduction of new products, services or technologies by our competitors;
failure to meet or exceed financial and development projections we may provide to the public;
failure to meet or exceed the financial and development projections of the investment community;
the perception of the pharmaceutical industry by the public, legislatures, regulators and the investment community;
announcements of significant acquisitions, strategic collaborations, joint ventures or capital commitments by us or our competitors;
disputes or other developments relating to proprietary rights, including patents, litigation matters, and our ability to obtain patent protection for our technologies;
additions or departures of key personnel;
significant lawsuits, including patent or stockholder litigation;
if securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our business and stock;
changes in the market valuations of similar companies;
general market or macroeconomic conditions;
sales of its common stock by us or our stockholders in the future;
trading volume of our common stock;
failure to maintain compliance with the listing requirements of The Nasdaq Global Select Market;
announcements by commercial partners or competitors of new commercial products, clinical progress or the lack thereof, significant contracts, commercial relationships or capital commitments;
adverse publicity generally, including with respect to other products and potential products in such markets;
the introduction of technological innovations or new therapies that compete with our potential products;
changes in the structure of health care payment systems;
disruptions in the financial markets;
the impact of political instability and military conflict, such as geopolitical tensions between the United States and China, the conflicts in the Middle East, and the conflict in Ukraine, which has resulted in instability in the global financial markets and export control; and
period-to-period fluctuations in our financial results.
Moreover, the stock markets in general have experienced substantial volatility that has often been unrelated to the operating performance of individual companies. These broad market fluctuations may engagealso adversely affect the trading price of our common stock.
In the past, following periods of volatility in misconduct or other improper activities, including noncompliance with regulatorythe market price of a company’s securities, stockholders have often instituted class action securities litigation against those companies. Such litigation, if instituted, could result in substantial costs and diversion of management attention and resources, which could significantly harm our profitability and reputation.
Additionally, a decrease in our stock price may cause our common stock to no longer satisfy the continued listing standards of Nasdaq. If we are not able to maintain the requirements for listing on Nasdaq, we could be delisted, which could have a materially adverse effect on our ability to raise additional funds as well as the price and requirements and insider trading.liquidity of our common stock.
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We are exposedwill continue to the riskincur costs and demands upon management as a result of fraud or other misconduct by our employees, principal investigators, consultants and commercial partners. Misconduct by these parties could include intentional failures, reckless and/or negligent conduct or unauthorized activities that violates (i)complying with the laws, rules and regulations affecting public companies.
We will continue to incur significant legal, accounting and other expenses that we did not incur as a private company, including costs associated with public company reporting requirements. We will also incur costs associated with corporate governance requirements, including requirements under the laws, rules and regulations of the FDASEC as well as the Nasdaq rules. These laws, rules and regulations are expected to increase our legal and financial compliance costs and to make some activities more time consuming and costly. For example, some members of our management team have not previously managed and operated a public company. These executive officers and other regulatory authorities,personnel will need to devote substantial time to gaining expertise regarding operations as a public company and compliance with applicable laws and regulations. These laws, rules and regulations also may make it difficult and expensive for us to maintain directors’ and officers’ liability insurance. As a result, it may be more difficult for us to attract and retain qualified individuals to serve on our board of directors or as executive officers, which may adversely affect investor confidence and could cause our business or stock price to suffer.
We may become involved in securities litigation that could divert management’s attention and harm our business, and insurance coverage may not be sufficient to cover all costs and damages.
We may be exposed to securities litigation even if no wrongdoing occurred. Litigation is usually expensive and diverts management’s attention and resources, which could adversely affect our business and cash resources. We may become involved in such litigation, and our stock price may fluctuate for many reasons, including those lawsas a result of public announcements regarding the progress of our development efforts or the development efforts of current or future collaboration partners or competitors, the addition or departure of our key personnel, the announcement of the strategic restructuring, variations in our quarterly operating results and changes in market valuations of biopharmaceutical and biotechnology companies. This risk is especially relevant to us because biopharmaceutical and biotechnology companies have experienced significant stock price volatility in recent years. When the market price of a stock has been volatile, as our stock price may be, holders of that stock have occasionally brought securities class action litigation against the company that issued the stock. If any of our stockholders were to bring a lawsuit of this type against us, even if the lawsuit is without merit, it could result in substantial costs for defending the lawsuit and diversion of the time, attention and resources of our board of directors and management, which could significantly harm our profitability and reputation.
Anti-takeover provisions in our charter documents and under Delaware law could make an acquisition of us more difficult and may prevent attempts by our stockholders to replace or remove our management.
Provisions in our certificate of incorporation and bylaws may delay or prevent an acquisition or a change in management. In addition, because we will be incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law (“DGCL”), which prohibits stockholders owning in excess of 15% of or outstanding voting stock from merging or combining with us. Although we believe these provisions collectively will provide for an opportunity to receive higher bids by requiring potential acquirors to negotiate with our board of directors, they would apply even if the reportingoffer may be considered beneficial by some stockholders. In addition, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove then current management by making it more difficult for stockholders to replace members of true, completethe board of directors, which is responsible for appointing the members of management.
Our amended and accurate informationrestated certificate of incorporation provides that the Court of Chancery of the State of Delaware is the exclusive forum for substantially all disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or other employees, and could make it more costly for stockholders to bring a claim against us.
Our amended and restated certificate of incorporation and amended and restated bylaws, provide, among other things, that that the Court of Chancery of the State of Delaware (or, in the event that the Court of Chancery does not have jurisdiction, the federal district court for the District of Delaware or other state courts of the State of Delaware) generally will be the exclusive forum for any derivative action or proceeding brought on our behalf, any action asserting a claim of breach of fiduciary duty, any action asserting a claim against us arising pursuant to the DGCL, our amended and restated certificate of incorporation or our amended and restated bylaws, or any action asserting a claim against us that is governed by the internal affairs doctrine; provided that, the exclusive forum provision will not apply to suits brought to enforce any liability or duty created by the Exchange Act or any other claim for which the federal courts have exclusive jurisdiction; and provided further that, if and only if the Court of Chancery of the State of Delaware dismisses any such authorities, (ii) manufacturing standards, (iii)action for lack of subject matter jurisdiction, such action may be brought in another state or federal court sitting in the State of Delaware.
To prevent having to litigate claims in multiple jurisdictions and the threat of inconsistent or contrary rulings by different courts, among other considerations, our amended and restated certificate of incorporation and the amended and restated bylaws further provide that the federal district courts of the United States of America will be
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the exclusive forum for resolving any complaint asserting a cause of action arising under the Securities Exchange Act of 1934 (the “Securities Act”). However, Section 22 of the Securities Act creates concurrent jurisdiction for federal and state data privacy, security, fraudcourts over all such Securities Act actions. Accordingly, both state and abusefederal courts have jurisdiction to entertain such claims, and other healthcareinvestors cannot waive compliance with the federal laws and rules and regulations thereunder. While the Delaware courts have determined that such choice of forum provisions are facially valid and several state trial courts have enforced such provisions and required that suits asserting Securities Act claims be filed in federal court, there is no guarantee that courts of appeal will affirm the enforceability of such provisions and a stockholder may nevertheless seek to bring a claim in a venue other than those designated in the United Statesexclusive forum provisions. In such instance, we would expect to vigorously assert the validity and abroadenforceability of the exclusive forum provisions of our amended and (iv) lawsrestated certificate of incorporation and amended and restated bylaws. This may require significant additional costs associated with resolving such action in other jurisdictions and there is uncertainty that require the true, complete and accurate reporting of financial information or data. In particular, sales, marketing and business arrangementsprovision would be enforced by a court in the healthcare industry are subjectthose other jurisdictions. If a court were to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. Such misconduct also could involve the improper use of individually identifiable information, including, without limitation, information obtained in the course of clinical trials, creating fraudulent datafind either exclusive forum provision in our preclinical studiesamended and restated certificate of incorporation or clinical trialsamended and restated bylaws to be inapplicable or illegal misappropriation of drug product,unenforceable in an action, we may incur further significant additional costs associated with litigating Securities Act claims in state court, or both state and federal court, which could result in regulatory sanctions and cause seriousseriously harm to our reputation. It is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from government investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations. Additionally, we are subject to the risk that a person or government could allege such fraud or other misconduct, even if none occurred. If any such actions are instituted against us and we are not successful in defending ourselves or asserting our rights, those actions could result in significant civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, exclusion from participating in government-funded healthcare programs, such as Medicare and Medicaid, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of noncompliance with these laws, contractual damages, reputational harm and the curtailment or restructuring of our operations, any of which could have a negative impact on our business, financial condition, results of operations, and prospects.
If we engage This exclusive forum provision may make it more expensive for stockholders to bring a claim than if the stockholders were permitted to select another jurisdiction and may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers or other employees or stockholders, which may discourage such lawsuits against us and our directors, officers and other employees and stockholders. Alternatively, if a court were to find the choice of forum provision contained in our amended and restated certificate of incorporation or amended and restated bylaws to be inapplicable or unenforceable in an acquisition, reorganization or business combination, we will incur a variety of risks potentially adversely affecting our business operations or our stockholders.
From time to time we have considered, and we will continue to consider in the future, strategic business initiatives intended to further the expansion and development of our business. These initiatives may include
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acquiring businesses, technologies, or products or entering into a business combination with another company. If we pursue such a strategy, we could, among other things:
issue equity securities dilutive to our current stockholders' percentage ownership;
incur substantial debt straining our operations;
spend substantial operational, financial, and management resources to integrate new businesses, technologies, and products;
assume substantial actual or contingent liabilities;
reprioritize our development programs and even cease development and commercialization of our product candidates; or
merge with, or otherwise enter into a business combination with, another company in which our stockholders would receive cash and/or shares of the other company on terms certain of our stockholders may not deem desirable.
Although we intend to evaluate and consider acquisitions, reorganizations, and business combinations in the future, we have no agreements or understandings with respect to any acquisition, reorganization, or business combination at this time.
Security breaches, cyber-attacks or other disruptions or incidents could expose us to liability and affect our business and reputation.
We are increasingly dependent on our information technology systems and infrastructure for our business. We, our collaborators and our service providers collect, store, and transmit sensitive information including intellectual property, proprietary business information, clinical trial data and personal information in connection with our business operations. The secure maintenance of this information is critical to our operations and business strategy. Some of this information could be an attractive target of criminal attack by third parties with a wide range of motives and expertise, including organized criminal groups, "hacktivists," patient groups, disgruntled current or former employees, nation-state and nation-state supported actors and others. Cyber-attacks are of ever-increasing levels of sophistication, and despite our security measures, our information technology and infrastructure may be vulnerable to such attacks or may be breached, including due to employee error or malfeasance. We have implemented information security measures to protect our systems, proprietary information and sensitive data, including the personal information of clinical trial participants against the risk of inappropriate and unauthorized external use and disclosure and other types of compromise. However, despite these measures, and due to the ever changing information cyber-threat landscape, we cannot guarantee that these measures will be adequate to detect, prevent or mitigate security breaches and other incidents andaction, we may be subject to data breaches through cyber-attacks, malicious code (such as viruses and worms), phishing attacks, social engineering schemes, and insider theft or misuse. Anyincur additional costs associated with resolving such breach could compromise our networks and the information stored there could be accessed, modified, destroyed, publicly disclosed, lost or stolen. If our systems become compromised, we may not promptly discover the intrusion. Likeaction in other companies in our industry, we have experienced attacks to our data and systems, including malware and computer viruses. Any security breach of other incident, whether real or perceived, would cause us to lose product sales, and suffer reputational damage and loss of customer confidence. Such incidents could result in costs to respond to, investigate and remedy such incidents, notification obligations to affected individuals, government agencies, credit reporting agencies and other third parties, legal claims or proceedings, and liability under our contracts with other parties and federal and state laws that protect the privacy and security of personal information. If a security breach, cyber-attack, or other disruption is the result of state-sponsored activities, it may be considered an "act-of-war", potentially making us ineligible for reimbursement under our insurance policies covering such attacks. Any one of these events could cause our business to be materially harmed and our results of operations would be adversely impacted.
The occurrence of natural disasters, including a tornado, an earthquake, or fire, or any material failure, weakness, interruption, cyber-attack, security incident, war or any other catastrophic event, could disrupt our operations or the operations of third parties who provide vital support functions to us,jurisdictions, which could have a material adverse effect on our business, results of operations,materially and financial condition.
We and the third-party service providers on which we depend for various support functions, such as data storage, are vulnerable to damage from catastrophic events, such as power loss, natural disasters, terrorism, physical theft, power loss, war, state-sponsored attacks, telecommunications failure and similar unforeseen events beyond our control, as well as from internal and external security breaches, malware and viruses, denial or degradation of service attacks, ransomware, cyber events and other disruptive problems. Such events could
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severely disrupt our operations and have a material adverse effect on our business, results of operations, financial condition, and prospects.
If a natural disaster, power outage, security incident or other event occurred that prevented us from using all or a significant portion of our offices or other facilities, damaged critical infrastructure such as our data storage facilities, financial systems, or manufacturing resource planning and quality systems, or that otherwise disrupted operations, it may be difficult or, in certain cases, impossible for us to continue our business for a substantial period of time. The disaster recovery and business continuity plans we have in place currently are limited and are unlikely to prove adequate in the event of a serious disaster or similar event. We may incur substantial expenses as a result of the limited nature of our disaster recovery and business continuity plans, which could have a material adverse effect on our business. In addition, the failure of our systems to operate effectively, maintenance problems, upgrading or transitioning to new platforms, or a breach in security could result in delays and reduce efficiency in our operations. Remediation of such problems could result in significant, unplanned capital investments.
Furthermore, parties in our supply chain may be operating from single sites, increasing their vulnerability to natural disasters or other sudden, unforeseen, and severe adverse events. If such an event were to affect our supply chain, it could have a material adverse effect on our business.
We are subject to numerous and varying data privacy and security laws, regulations and standards, and our failure to comply could result in penalties and reputational damage.
We are subject to domestic and foreign laws and regulations concerning data privacy, information security and the protection of personal information including health information. The legislative and regulatory landscape for privacy and data protection continues to evolve, and there has been an increasing focus on privacy and data protection issues which may affect our business and is expected to increase our compliance costs and exposure to liability. In the United States, numerous federal and state laws and regulations, including state security breach notification laws, federal and state health information privacy laws (including HIPAA), and federal and state consumer protection laws, govern the collection, use, disclosure, and protection of personal information. Each of these laws is subject to varying interpretations by courts and government agencies, creating complex compliance issues for us. For example, the California Consumer Privacy Act (CCPA) went into effect January 1, 2020. The CCPA, among other things, imposes new data privacy obligations on covered companies and provides expanded privacy rights to California residents, including the right to access, delete and opt out of certain disclosures of their information. The CCPA provides for civil penalties for violations, as well as a private right of action with statutory damages for certain data breaches, which may increase the frequency and likelihood of data breach litigation. Although the law includes limited exceptions, including for "protected health information" maintained by a covered entity or business associate, such exceptions may not apply to all of our operations and processing activities. Further, the California Privacy Rights Act (CPRA), recently passed in California. The CPRA imposes additional data protection obligations on covered businesses, including additional consumer rights processes, limitations on data uses, new audit requirements for higher risk data, and opt outs for certain uses of sensitive data. It also creates a new California data protection agency authorized to issue substantive regulations and could result in increased privacy and information security enforcement. The majority of the provisions will go into effect on January 1, 2023, and additional compliance investment and potential business process changes may be required. In addition, the CCPA has prompted a number of proposals for new federal and state privacy legislation that, if passed, could increase our potential liability, increase our compliance costs and adversely affect our business. If we fail to comply with applicable laws and regulations we could be subject to penalties or sanctions, including criminal penalties if we knowingly obtain or disclose individually identifiable health information in a manner that is not authorized or permitted by HIPAA or applicable state laws.
We are also or may become subject to rapidly evolving data protection laws, rules and regulations in foreign jurisdictions, including Canada, Australia, Brazil, Georgia and Europe. For example, the European Union General Data Protection Regulation (GDPR) governs certain collection and other processing activities involving personal data about individuals in the European Economic Area and the United Kingdom. Among other things, the GDPR imposes requirements regarding the security of personal data, the rights of data subjects to access and delete personal data, requires having lawful bases on which personal data can be processed and transferred outside of the European Economic Area, requires changes to informed consent practices, and requires more detailed notices for clinical trial participants and investigators. In addition, the GDPR imposes substantial fines for breaches and violations (up to the greater of €20 million or 4% of our annual global revenue). The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies and obtain compensation for damages resulting from violations of the GDPR. Relatedly, following
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the United Kingdom's withdrawal from the European Economic Area and the European Union, and the expiry of the transition period, companies will have to comply with the GDPR and the GDPR as incorporated into United Kingdom national law, the latter regime having the ability to separately fine up to the greater of £17.5 million or 4% of global turnover. The relationship between the United Kingdom and the European Union in relation to certain aspects of data protection law remains unclear, for example around how data can lawfully be transferred between each jurisdiction, which exposes us to further compliance risk.
Compliance with U.S. and foreign privacy and security laws, rules and regulations could require us to take on more onerous obligations in our contracts, require us to engage in costly compliance exercises, restrict our ability to collect, use and disclose data, or in some cases, impact our or our partners' or suppliers' ability to operate in certain jurisdictions. Each of these constantly evolving laws can be subject to varying interpretations. If we fail to comply with any such laws, rules or regulations, we may face government investigations and/or enforcement actions, fines, civil or criminal penalties, private litigation or adverse publicity that could adversely affect our business, financial condition and results of operations.
U.S. tax legislationWe do not anticipate that we will pay any cash dividends in the foreseeable future.
The current expectation is that we will retain our future earnings, if any, to fund the development and future changesgrowth of our business. As a result, capital appreciation, if any, of our common stock will be our stockholders’ sole source of gain, if any, for the foreseeable future.
An active trading market for our common stock may not develop and our stockholders may not be able to applicable U.S. tax laws and regulationsresell their shares of common stock for a profit, if at all.
An active trading market for our shares of common stock may never develop or be sustained. If an active market for our common stock does not develop or is not sustained, it may be difficult for our stockholders to sell their shares at an attractive price or at all.
Future sales of a substantial number of shares by existing stockholders, or the perception that such sales could occur, could cause our stock price to decline.
If our existing stockholders sell, or indicate an intention to sell, substantial amounts of our common stock in the public market, the trading price of our common stock could decline. We are unable to predict the effect that sales may have a material adverse effect on the prevailing market price of our common stock. In addition, shares of our common stock that are either subject to outstanding options or reserved for future issuance under our equity incentive plan will be eligible for sale in the public market to the extent permitted by the provisions of various vesting schedules. If these additional shares of common stock are sold, or if it is perceived that they will be sold, in the public market, the trading price of our common stock could decline.
If equity research analysts do not publish research or reports, or publish unfavorable research or reports, about us, our business financial conditionor our market, our stock price and results of operations.trading volume could decline.
Changes in laws and policy relating to taxes may have an adverse effect onThe trading market for our business, financial condition and results of operations. For example, the U.S. government enacted significant tax reform legislation in 2017, which, as modifiedcommon stock is influenced by the CARES Act, contains, certain provisions whichresearch and reports that equity research analysts publish about us and our business. Equity research analysts may elect not to provide research coverage of our common stock, and such lack of research coverage may adversely affect us. Changes include, but arethe market price of our common stock. In the event we do have equity research analyst coverage, we will not limitedhave any control over the analysts, or the content and opinions included in their reports. The price of our common stock could decline if one or more equity research analysts downgrade our stock or issue other unfavorable commentary or research. If one or more equity research analysts ceases coverage of us or fails to a federal corporate income tax ratepublish reports on us regularly, demand for our common stock could decrease, which in turn could cause our stock price or trading volume to 21% for tax years beginning after December 31, 2017, a reduction to the maximum deduction allowed for net operating losses generated in tax years after December 31, 2017, eliminating carrybacks of net operating losses for tax years beginning after December 31, 2020, providing for indefinite carryforwards for losses generated in tax years after December 31, 2017, imposing significant additional limitations on the deductibility of interest, allowing for the accelerated expensing of capital expenditures, and putting into effect the migration from a "worldwide" system of taxation to a largely territorial system. The legislation is unclear in many respects and may continue to be subject to potential amendments, technical corrections, interpretations and implementing regulations by the Treasury and Internal Revenue Service, any of which may mitigate or increase certain adverse effects of the legislation. In addition, it is unclear how these U.S. federal income tax changes will affect state and local taxation. Generally, future changes in applicable U.S. tax laws and regulations, or their interpretation and application could have an adverse effect on our business, financial condition and results of operations.decline.
We may be subjectare expected to claims that our employees have wrongfully used or disclosed alleged trade secretstake advantage of their former employers. If we are not ablereduced disclosure and governance requirements applicable to adequately prevent disclosure of trade secretssmaller reporting companies and other proprietary information, the value of our technology and products could be significantly diminished.
As is common in the biotechnology and pharmaceutical industries, we employ individuals who were previously employed at other biotechnology or pharmaceuticalemerging growth companies, including our competitors or potential competitors. Although we seek to protect our ownership of intellectual property rights by ensuring that our agreements with our employees, collaborators and other third parties with whom we do business include provisions requiring such parties to assign rights in inventions to us, we may be subject to claims that these employees, or we, have inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former employers. We may also be subject to claims that former employers or other third parties have an ownership interest in our patents. Litigation may be necessary to defend against these claims. There is no guarantee of success in defending these claims, and if we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, validity or enforceability of, or right to use, valuable intellectual property. Even if we are successful in defending against these claims, litigationwhich could result in substantial costs and be a distractionour common stock being less attractive to management.investors.
We rely on trade secretshave a public float of less than $250 million and therefore qualify as a smaller reporting company under the rules of the SEC. As a smaller reporting company, we are able to protect our proprietary technologies, especially where we do not believe patent protection is appropriate or obtainable. However, trade secrets are difficult to protect. We rely in part on confidentiality agreements with our employees, consultants, outside scientific collaborators, sponsored researchers and other advisors to protect our trade secrets and other proprietary information. These agreements may not effectively preventtake advantage of reduced disclosure of confidential information and may not provide an adequate remedy in the event of unauthorized disclosure of confidential information. In addition, others may independently discover our trade secrets and proprietary information. For example, the FDA, as part of its Transparency Initiative, is currently considering whether to make additional information publicly available on a routine basis, including information that we may
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considerrequirements, such as simplified executive compensation disclosures and reduced financial statement disclosure requirements in our SEC filings. Decreased disclosures in our SEC filings due to our status as a smaller reporting company may make it harder for investors to analyze our results of operations and financial prospects. We cannot predict if investors will find our common stock less attractive if we rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock price may be more volatile. We may take advantage of the reporting exemptions applicable to a smaller reporting company until we are no longer a smaller reporting company, which status would end once we have a public float greater than $250 million. In that event, we could still be a smaller reporting company if our annual revenues were below $100 million and we have a public float of less than $700 million.
We are an emerging growth company (“EGC”), as defined in the Jumpstart Our Business Startups Act of 2012, as amended. For as long as we continue to be trade secretsan EGC, we may take advantage of exemptions from various reporting requirements that are applicable to other public companies that are not EGCs, including not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act, reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements and exemptions from the requirements of holding nonbinding advisory votes on executive compensation and stockholder approval of any golden parachute payments not previously approved. We may remain an EGC or other proprietary information,until the earlier of (a) December 31, 2026, (b) the last day of the fiscal year in which we have total annual gross revenue of at least $1.235 billion or more, (c) the date we are deemed to be a large accelerated filer, which requires the market value of our common stock that is held by non-affiliates to exceed $700.0 million as of the prior June 30th, and it is not clear at(d) the present time howdate on which we have issued more than $1.0 billion in non-convertible debt during the FDA's disclosure policiesprior three-year period.
Changes in tax laws may change in the future, if at all. Costlymaterially adversely affect our business, prospects, financial condition and time-consuming litigationoperating results.
New tax laws, statutes, rules, regulations or ordinances could be necessary to enforce and determine the scope of our proprietary rights, and failure to obtain or maintain trade secret protectionenacted at any time, which could adversely affect our competitive business, position.prospects, financial condition and operating results. Further, existing tax laws, statutes, rules, regulations or ordinances could be interpreted, changed, modified or applied adversely to us. For example, the Tax Act, the CARES Act, and the IRA enacted many significant changes to the U.S. tax laws. Future guidance from the Internal Revenue Service and other tax authorities with respect to such legislation may affect us, and certain aspects of such legislation could be repealed or modified in future legislation. Such tax law changes could have a material adverse impact on us. In addition, it is uncertain if and to what extent various states will conform to newly enacted federal tax legislation. While it is too early to assess the overall impact of these changes, as these and other tax laws and related regulations are revised, enacted, and implemented, our financial condition, results of operations, and cash flows could be materially adversely impacted.
The laws of some foreign countriesOur ability to use NOL carryforwards and other tax attributes may be limited.
We have incurred losses during our history, and we do not protect proprietary rightsexpect to become profitable in the samenear future and may never achieve profitability. To the extent as dothat we continue to generate taxable losses, unused losses will carry forward to offset future taxable income, if any, until such unused losses expire, if at all. As of December 31, 2023, we had U.S. federal NOL carryforwards and state NOL carryforwards of approximately $237.8 million and $170.4 million, respectively. Under current law, U.S. federal NOL carryforwards generated in taxable periods beginning after December 31, 2017, may be carried forward indefinitely, but the lawsdeductibility of such NOL carryforwards is limited to 80% of taxable income. It is uncertain if and to what extent various states will conform to federal law. In addition, under Sections 382 and 383 of the United States,Code, federal NOL carryforwards and weother tax attributes may encounter significant problemsbecome subject to an annual limitation in securing and defending our intellectual property rights outside the United States.
Many companies have encountered significant problems in protecting and defending intellectual property rights in certain countries. The legal systemsevent of certain countries, particularly certain developing countries, do not always favorcumulative changes in ownership. An “ownership change” pursuant to Section 382 of the enforcementCode generally occurs if one or more stockholders or groups of patents, trade secrets,stockholders who own at least 5% of a company’s stock increase their ownership by more than 50 percentage points over their lowest ownership percentage within a rolling three-year period. Our ability to utilize our NOL carryforwards and other intellectual property rights, particularly those relatingtax attributes to pharmaceutical products, which could make it difficult for us to stop infringementoffset future taxable income or tax liabilities may be limited as a result of our patents, misappropriation of our trade secrets,ownership changes or marketing of competing products in violation of our proprietary rights. Proceedings to enforce our intellectual property rights in foreign countriesother transactions. Similar rules may apply under state tax laws. If we earn taxable income, such limitations could result in substantial costs, divertincreased future income tax liability to us, and our efforts and attention from other aspects of our business, and put our patents in these territories at risk of being invalidated or interpreted narrowly, or our patent applications at risk of not being granted, andfuture cash flows could provoke third parties to assert claims against us. We may not prevail in all legal or other proceedings that we may initiate and, if we were to prevail, the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.adversely affected.

Item 1B. Unresolved Staff Comments
None.

Item 1C. Cybersecurity
We recognize the critical importance of protecting the confidentiality, integrity and availability of our business operations and systems. With this in mind, we have implemented and maintain an ongoing cybersecurity risk management program, under the oversight of our Board of Directors that is focused on identifying, assessing,
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managing, and mitigating cybersecurity risk. Our cybersecurity policies, standards, processes and practices incorporate several standards, specifications, and requirements from the National Institute of Standards and Technology (“NIST”) Cybersecurity Framework, and other applicable industry standards. In general, we seek to address cybersecurity risks through a cross-functional approach that is focused on preserving the confidentiality, security and availability of the information that we collect and store by identifying, preventing and mitigating cybersecurity threats and effectively responding to cybersecurity incidents if they occur.
Cybersecurity Risk Management and Strategy; Effect of Risk
To identify and assess material risks from cybersecurity threats, we maintain a cybersecurity program to ensure our systems are effective and prepared for information security risks. We consider risks from cybersecurity threats alongside other company risks as part of our overall risk assessment process. We employ a range of tools and services, including regular network and endpoint monitoring to inform our risk identification and assessment, as well as undertaking the following activities:
monitor emerging data protection laws and implement changes to our processes that are designed to comply with such laws;
through our policies, practices and contracts (as applicable), require employees, as well as third parties that provide services on our behalf, to treat confidential information and data with care;
employ technical safeguards that are designed to protect our information systems from cybersecurity threats, including firewalls, device encryption, multi-factor authentication, advanced threat protection for emails, anti-virus and anti-malware functionality and access controls, which are evaluated and improved from time to time;
conduct regular phishing email simulations and cybersecurity training for all employees and contractors with access to our email systems to enhance awareness and responsiveness to possible threats; and
employ multiple backup systems for our data stored on our servers or other information systems.

As part of the above processes, we regularly engage with third-party cybersecurity vendors to provide a range of services in furtherance of our cybersecurity program, including monitoring our cybersecurity systems and processes to help identify areas for continued focus, improvement and compliance. In addition, we also have a process to assess and review the cybersecurity practices of third-party vendors and service providers, including through the use of contractual security requirements and performing diligence, as appropriate.
We face risks from cybersecurity threats that, if realized, are reasonably likely to materially affect us, including our operations, business strategy, results of operations, or financial condition. For more information, see the section in our risk factors under the heading “Our internal information technology systems, or those of our vendors, collaborators or other contractors or consultants, may fail or suffer cybersecurity incidents, loss of data, and other disruptions, which could result in a material disruption of our product development programs, compromise sensitive information related to our business or prevent us from accessing critical information, potentially exposing us to liability or otherwise adversely affecting our business.” which disclosures are incorporated by reference herein.
Cybersecurity Governance; Management
Cybersecurity is an important part of our risk management processes and an area of focus for our Board of Directors and management. Our Board of Directors has delegated the oversight of cybersecurity risks to our Audit Committee, which oversees management’s implementation of our cybersecurity program.
Our Audit Committee receives periodic updates from management of our cybersecurity program and risks, including, as necessary, any material cybersecurity threat risks or incidents, as well as the steps management has taken to respond to such risks. Members of our Audit Committee are also encouraged to engage in conversations with management on cybersecurity-related news events and discuss any updates to our cybersecurity risk management and strategy programs. The Committee reports to the full Board of Directors regarding its activities and risk management functions, including those related to cybersecurity.
Our cybersecurity program, which is discussed in greater detail above, is led by our Chief Financial Officer with the help of our legal and human resources teams. Such individual has prior work experience in various roles involving managing information security and developing cybersecurity strategy and is responsible for supervising both our internal personnel and our retained third-party cybersecurity vendors. As discussed above, this management team member reports to the Audit Committee of our Board of Directors about cybersecurity related matters, periodically.
Our management team is informed about and monitors the prevention, mitigation, detection, and remediation of cybersecurity incidents through their management of, and participation in, the cybersecurity risk management and strategy processes described above. In the last three fiscal years, we have not experienced any material cybersecurity incidents.
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Item 2. Properties

Our corporate operations are based in San Francisco, California, our clinical and regulatory operations are based in Newton, Massachusetts, and our discovery and research programs are based in Uniondale, New York. We currently occupy 100 square feet of temporary corporate office space in San Francisco under a bi-monthly lease. We also currently lease 6,157 square feet of clinical and regulatory space in Newton, Massachusetts underIn July 2021, we entered into a lease that expires in June 2024 and 43,000 square feet of research and discovery space in Uniondale, New York under a lease that expires in June 2026 from NovaPark LLC, a related party. See "Certain Relationships and Related Party Transactions". In addition to these facilities, we rentagreement for approximately 2,10513,424 square feet of office and laboratory space in Fort Lee, New Jersey underBoston, Massachusetts, which serves as our corporate headquarters.The lease commenced in February 2022. The lease term is for eight years and expires February 28, 2030 and does not contain an option to renew. The initial annual rent was $1,235,008 with a lease expiring in March 2022 and will not be renewed.

3% annual increase. We believe substantially all of our facilities are suitableproperty and adequate for our current needs,equipment is in good condition and that we will be ablehave sufficient capacity to obtainmeet our current operational needs. See Note 11 to our consolidated financial statements included in Item 8 of this Annual Report on Form 10-K for additional space, as needed, on commercially reasonable terms.information.

Item 3. Legal Proceedings
We are not currently a party to any material legal proceedings. From time to time, we may be involved inare subject to various legal proceedings, or subject to claims incident toand administrative proceedings that arise in the ordinary course of our business activities. Although the results of the litigation and claims cannot be predicted with certainty, as of the date of this report, we do not believe we are party to any claim, proceeding or litigation the outcome of which, if determined adversely to us, would individually or in the aggregate be reasonably expected to have a material adverse effect on our business. Regardless of the outcome, such proceedings or claimslitigation can have an adverse impact on us because of defense and settlement costs, diversion of management resources and other factors, and there can be no assurances that favorable outcomes will be obtained.factors.
Item 4. Mine Safety Disclosures
None.Not applicable.
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Part II
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
Market Information
Our common stock trades under the symbol “ANGN”“ELTX” on the Nasdaq Global Select Market and has been publicly traded under this symbol since February 5, 2021. Prior to this time, there was no public market for our common stock.
Use of Proceeds from the Initial Public Offering and the Concurrent Private Placement
On February 9, 2021, we closed our Initial Public Offering of 5,750,000 shares of our common stock at a public offering price of $16.00 per share, which includes the full exercise by the underwriters (Cowen and Company, LLC, Stifel, Nicolaus & Company, Incorporated, H.C. Wainwright & Co., LLC and Oppenheimer & Co. Inc) of their option to purchase an additional 750,000 shares of common stock. Concurrently, we entered into a stock purchase agreement (the “Stock Purchase Agreement”) with Vifor Pharma, pursuantJune 1, 2023, prior to which we agreed to sell 1,562,500 shares of our common stock to Vifor Pharma at a purchase price of $16.00 per share (the Concurrent Private Placement), equal to the offering price per share in our IPO. All of the shares of common stock issued and sold in our IPO were registeredit was traded under the Securities Act pursuant to registration statements on Form S-1, as amended (Registration No. 333-252177), which were declared effective by the SEC on February 4, 2021.
The Initial Public Offering and Concurrent Private Placement, which both closed on February 9, 2021, generated aggregate net proceeds of approximately $107.0 million, after deducting the underwriting discounts and commissions, private placement fee and estimated offering expenses of $10.0 million. As of December 31, 2021, we have used approximately 50% of the aggregate net proceeds from our IPO.
There has been no material changes in the planned use of proceeds from our IPO as described in our final prospectus filed with the SEC on February 5, 2021 pursuant to Rule 424(b)(4), except that given the clinical trial data on ANG-3777 reported in the fourth quarter of 2021, we no longer intend to use the Use of Proceeds for the clinical development of ANG-3777.There are no funds budgeted for additional clinical trials of ANG-3777.symbol “ANGN”.
Holders of Record
As of March 30, 2022,26, 2024, there were approximately 150245 holders of record of shares of our common stock. This number does not reflect the beneficial holders of our common stock who hold shares in street name through brokerage accounts or other nominees.
Unregistered Sales of Equity Securities

On
December 22, 2023, we entered into a Subscription Agreement (the “Subscription Agreement”) with GKCC, LLC (the “Purchaser”), an entity controlled by one of our directors, providing for the issuance and sale by us to the Purchaser of an aggregate of 1,213,000 shares of our common stock, par value $0.01 per share, at a purchase price per share of $5.81 (the “Offering”). The gross proceeds were approximately $7.0 million.
The issuance of these shares was pursuant to a private placement exemption from registration afforded by Section 4(a)(2) of the Securities Act of 1933, as amended, and Rule 506 of Regulation D thereunder and similar exemptions under applicable state laws. We plan to use the proceeds of the Offering for the advancement of our development pipeline, as well as for working capital and general corporate purposes.
Repurchases of Equity Securities
None.
Dividend Policy
We have never declared or paid cash dividends on our common stock. We intend to retain all available funds and any future earnings, if any, to fund the development and expansion of our business and we do not anticipate paying any cash dividends in the foreseeable future. Any future determination related to dividend policy will be made at the discretion of our board of directors after considering our financial condition, results of operations, capital requirements, business prospects and other factors the board of directors deems relevant, and subject to the restrictions contained in any future financing instruments.

Item 6. Reserved[Reserved]

Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations
You should read the following discussion and analysis of our financial condition and results of operations together with our consolidated financial statements and the related notes appearing elsewhere in this Annual Report on Form 10-K. In addition to the historical financial information, this discussion contains forward-looking statements that involve risk, assumptions and uncertainties, such as statements of our plans, objectives, expectations, intentions, forecasts and projections. Our actual results and the timing of selected events could differ materially from those discussed in these forward-looking statements as a result of several factors, including those set forth under the section of this Annual Report on Form 10-K titled "Risk Factors," which you should read carefully read to gain an
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understanding of the important factors that could cause actual results to differ materially from our forward-looking statements. Please also see the section titled "Forward-Looking Statements" at the beginning of this report.
Overview
We are a clinical-stage biopharmaceuticalbiotechnology company focused onpioneering the discovery, development and commercialization of novel small molecule therapeutics to address chronic and progressive fibrotic diseases. Our goal is to transform the treatment paradigmimmunotherapies for patients with limited treatment options and poor outcomes suffering from these potentially life-threatening conditions for which there are no approved medicines or where existing approved medicinescancer and infectious disease. Our proprietary Amphiphile (“AMP”) technology is designed to mobilize the body’s immune response by preferentially targeting our product candidates to the lymph nodes with the goal of generating a robust T cell response.Recent advances have limitations. Our lead product candidate, ANG-3070, is a highly selective oral tyrosine kinase receptor inhibitor (TKI) in developmentidentified T cell responses as a key component of effective cancer immunotherapy and we believe our AMP technology can generate a robust T cell response that can potentially provide meaningful clinical benefit.
We believe the therapeutic utility of currently approved and development stage immunotherapies are limited in many cases due to their inability to sufficiently localize to lymph nodes and adequately engage with the critical immune cells responsible for stimulating adaptive immunity.Our AMP technology is specifically intended to localize
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payloads to lymph nodes leading to the generation of a robust T cell response that we believe is critical to generate an anticancer immune response.
We have developed our cancer vaccine product candidates to target biologically validated tumor mutation drivers using known neoantigens.This strategy results in an “off-the-shelf” therapeutic option allowing patients to receive treatment for fibrotic diseases, particularly inwithout delay due to manufacturing timelines and costs associated with personalized vaccine approaches.
Our clinical and preclinical pipeline includes the kidney and lung. Enrollment is ongoinglymph node targeted therapeutic cancer vaccines ELI-002, currently being evaluated in a dose-finding Phase 2 trial of ANG-3070clinical program, designed to stimulate an immune response against mutant KRAS cancers, ELI-007, currently being evaluated in primary proteinuric kidney diseases (PPKD) and we expect to file an IND in idiopathic pulmonary fibrosis (IPF) by the end of 2022. We are also continuing to develop oura preclinical programs. Our ROCK2 program is targeted towards the treatment of fibrotic diseases. Our CYP11B2 program is targeted towards diseases related to aldosterone synthase dysregulation.
Prior to January 2022 our lead product was ANG-3777, a hepatocyte growth factor (HGF) mimetic we were evaluating in multiple indications of acute organ injury, including delayed graft function (DGF) andstudy for the treatment of AKI associated with cardiac surgery involving cardiopulmonary bypass (CSA-AKI). In 2021, we also studied ANG-3777mutant v-raf murine sarcoma viral oncogene homolog B1 (“BRAF”)-driven cancers, and ELI-008, currently being evaluated in a preclinical study for use in the treatment of mutated tumor protein p53 (“TP53”) expressing cancers.We believe that each of our cancer vaccine product candidates, if approved, have the potential to improve the lives of patients with severe COVID-19 related pneumonia at high risk for acute respiratory distress syndrome (ARDS). On October 26, 2021, we announcedsuffering from solid tumors arising due to specific oncogenic driver mutations.
Our operations to date have been financed primarily by aggregate net proceeds of $106.6 million from the Phase 3 trialissuance of ANG-3777 in DGF did not achieve its primary endpointcommon stock, convertible preferred stock, convertible notes, and the data were not expected to be sufficient evidence to support an indication inexercise of stock options and common stock warrants and proceeds from the studied DGF population. On December 9, 2021,Merger. Since inception, we announced the Phase 2 trial of ANG-3777 in CSA-AKI did not achieve its primary endpoint. We do not intend to continue the clinical development plan for ANG-3777 set forth in the Vifor License, whichhave had included a Phase 3 study in CSA-AKI and a Phase 4 confirmatory study in donor kidney transplant patients who were at risk for developing DGF, given we do not believe the earlier Phase 2 and Phase 3 clinical trial results in the respective indications support a regulatory approval. We have no funds budgeted for additional clinical trials for ANG-3777.
We do not have any products approved for sale and have not generated any revenue from product sales since our inception and do not expect to generate revenue from product sales unless we successfully develop and we or our collaborators commercialize our product candidates, which we do not expect to occur for several years, if ever.significant annual operating losses. Our net losses were $54.6loss was $35.2 million and $80.1$28.2 million for the years ended December 31, 20212023 and 2020,2022, respectively. As of December 31, 2021,2023, we had an accumulated deficit of $215.1 million.$142.2 million and $12.9 million in cash and cash equivalents.
Elicio Operating Company, Inc. (“Former Elicio”) was incorporated in Delaware as Vedantra Pharmaceuticals Inc. in August 2011. In December 2018, Former Elicio formed a wholly owned subsidiary, Elicio Securities Corporation, a Massachusetts corporation.
On January 17, 2023, Former Elicio entered into a definitive merger agreement (the “Merger Agreement”) with Angion Biomedica Corp (“Angion”), a clinical-stage biotechnology company, and Arkham Merger Sub, Inc., a wholly owned subsidiary of Angion (“Merger Sub”), pursuant to which Merger Sub merged with and into Former Elicio, with Former Elicio surviving the merger as a wholly owned subsidiary of Angion (the “Merger”).
On June 1, 2023, the Merger was completed in accordance with the terms and conditions of the Merger Agreement and Angion changed its name from “Angion Biomedica Corp.” to “Elicio Therapeutics, Inc.” Immediately following the consummation of the Merger, there were approximately 9.7 million shares of our common stock outstanding on a fully-diluted basis, with Former Elicio equity holders collectively owning approximately65.2% of the Company and Angion equity holders collectively owning approximately34.8%of the Company, in each case on a fully diluted basis. The Merger was accounted for as a reverse recapitalization, with Former Elicio being treated as the acquirer for accounting purposes. As a result of the Merger, the net assets of Angion were recorded at their acquisition-date fair value, which approximated book value due to the short-term nature of the instruments, in the financial statements of Former Elicio and the reported operating results prior to the Merger were those of Former Elicio.
We are currently facing substantial doubt about our ability to continue as a going concern, given our cash position and cash runway. We believe that our cash on hand will enable us to fund our operations into the third quarter of 2024 based on our current plan. This period could be shortened if there are any significant increases in planned or actual spending on development programs or more rapid progress of development programs than anticipated. There is no assurance that financing will be available when needed to allow us to continue as a going concern. Our losses from operations, negative operating cash flows and accumulated deficit, as well as the additional capital needed to fund operations for at least twelve months following the issuance of the consolidated financial statements, raise substantial doubt about our ability to continue as a going concern. We expect to incur substantial expenditures in the foreseeable future for the development of our product candidates and will require additional financing to continue this development. We plan to address this condition through the sale of common stock in public offerings and/or private placements, debt financings, or through other capital sources, including licensing arrangements, partnerships and collaborations with other companies or other strategic transactions, but there is no assurance these plans will be completed successfully or at all.If we are unable to obtain additional capital when and as needed to continue as a going concern, we might have to further reduce or scale back our operations and/or liquidate our assets, and the values we receive for our assets in liquidation or dissolution could be significantly lower than the values reflected in our financial statements.
Our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K have been prepared on a basis that assumes that we will continue as a going concern, which contemplates the realization of assets and satisfaction of liabilities in the normal course of business. Our consolidated financial statements do not include any adjustments relating to the recoverability and classification of recorded asset amounts or the amounts and classification of liabilities that might be necessary should we be unable to continue as a going concern.
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Cash used to fund operating expenses is impacted by the timing of when we pay these expenses, as reflected in the change in our accounts payable and accrued expenses. We expect to continue to incur net losses for the foreseeable future. Asfuture, and we expect our research and development expenses, general and administrative expenses, and capital expenditures will continue to increase. In particular, we expect our expenses to increase as we continue our development of, and seek regulatory approvals for, our product candidates, as well as hire additional personnel, pay fees to outside consultants, attorneys and accountants, and incur other increased costs associated with being a public company. In addition, if and when we seek and obtain regulatory approval to advance ANG-3070commercialize any product candidate, we will also incur increased expenses in connection with commercialization and marketing of any such product. Our net losses may fluctuate significantly from quarter-to-quarter and year-to-year, depending on the timing of our clinical trials and our expenditures on other product candidates through preclinicalresearch and development activities. We anticipate that our expenses will increase significantly in connection with our ongoing activities, as we:
• advance our lead product candidate, ELI-002, to late stage clinical trials;
• advance our preclinical programs to clinical trials;
• expand our pipeline of product candidates;
• seek regulatory approval for our investigational medicines;
• maintain, expand, protect and defend our intellectual property portfolio;
• acquire or in-license technology;
• expand our clinical, scientific, management and administrative teams; and
• operate as a public company.
We believe that our cash on hand will enable us to fund our operations into the third quarter of 2024 based on our current plan. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. To finance our operations beyond that point we will need to raise additional capital, which cannot be assured. Our losses from operations, negative operating losses may increase over time.cash flows and accumulated deficit, as well as the additional capital needed to fund operations for at least twelve months following the issuance of the consolidated financial statements, raise substantial doubt about our ability to continue as a going concern.
In addition, ifWe have not had any products approved for sale. We do not expect to generate any product sales unless and until we seeksuccessfully complete development and obtain regulatory approval for one or more of our product candidates. If we obtain regulatory approval for any of our wholly-owned product candidates, or those for which we retain the rightexpect to commercialize in the future, we would need to incur additional expenses as we expand our clinical, regulatory, quality, manufacturing and commercialization capabilities, incur significant commercialization expenses forrelated to product sales, marketing, sales, manufacturing and distributiondistribution. As a result, until such time, if ever, that we obtain marketing approval for suchcan generate substantial product candidates.
We rely on third parties in the conduct of our preclinical studies and clinical trials and for manufacturing and supply of our product candidates. We have no internal manufacturing capabilities, andrevenue, we expect to continuefinance our cash needs through equity offerings, debt financings or other capital sources, including collaborations, licenses or similar arrangements. However, we may be unable to relyraise additional funds or enter into such other arrangements when needed or on third parties, many of whom are single-source suppliers, for our preclinical studyfavorable terms, if at all. Any failure to raise capital as and clinical trial materials. In addition, we do not yetwhen needed could have a marketing or sales organization or commercial infrastructure. Accordingly,negative impact on our financial condition and on our ability to pursue our business plans and strategies, including our research and development activities. If we will incur significant expensesare unable to develop a marketing and sales organization and commercial infrastructure in advance of generating any product sales of wholly-owned product candidates or those for which we retain the right to commercialize. Furthermore,raise capital, we will need to make continued investment in development studies, registrationdelay, reduce or terminate planned activities and the development of commercial support functions including quality assurance and safety pharmacovigilance before we will be in a position to sell any of our product candidates, if approved.

reduce costs.
The Initial Public Offering and Concurrent Private Placement
The Initial Public Offering (IPO) and Concurrent Private Placement, which both closed on February 9, 2021, generated aggregate net proceeds of approximately $107.0 million, after deducting the underwriting discounts and commissions, private placement fee and estimated offering expenses payable by us.
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COVID-19 Update
The COVID-19 pandemic has placed strains on the providers of healthcare services, including the healthcare institutions where we conduct our clinical trials. These strains have resulted in institutions prohibiting the initiation of new clinical trials, enrollment in existing trials and restricting the on-site monitoring of clinical trials. We also follow FDA guidance on clinical trial conduct during the COVID-19 pandemic, including the remote monitoring of clinical data.
The global pandemic of COVID-19 continues to rapidly evolve. The extent to which COVID-19 may continue impact our business, including our clinical trials, and financial condition will depend on future developments, which are highly uncertain due to the continuing emergence of new variants and cannot be predicted with confidence, such as the ultimate duration of the pandemic and the effectiveness of actions taken in the United States and other countries to contain and treat the disease.
At this time, we do not expect any disruption in our supply chain of drugs necessary to conduct our clinical trials, and we believe we will be able to supply the drug needs of our clinical trials in 2022. However, we are continuing to evaluate our clinical supply chain in light of the COVID-19 pandemic.
License, Collaboration and Grant Agreements
License Agreement with Vifor Pharma
In November 2020, we granted Vifor Pharma, an exclusive, global (excluding Greater China), royalty-bearing license, for the commercialization of ANG-3777 in all Renal Indications, beginning with DGF and CSA-AKI. The Vifor License also grants Vifor Pharma exclusive rights, with a right to sublicense subject to our consent for certain specified conditions, to develop and manufacture ANG-3777 for commercialization in Renal Indications worldwide (excluding Greater China) in cooperation with us or independently. We retain the right to develop and commercialize combination therapy products combining ANG-3777 with our other proprietary molecules, subject to Vifor Pharma's right of first negotiation with respect to global (excluding Greater China) rights to such combination therapy products in the Renal Indications.
Pursuant to the Vifor License and specifically based upon the clinical development plan for ANG-3777 set forth in the Vifor License, we are entitled to receive $80 million in upfront and near-term clinical milestone payments, including $30 million in up-front cash that was received in November 2020, and a $30 million equity investment, a $5 million convertible note that subsequently converted into common stock with the IPO and $25 million of which was received in the Concurrent Private Placement with our IPO. We are also eligible to receive post-approval milestones of up to approximately $260.0 million and sales-related milestones of up to $1.585 billion, providing a total potential deal value of up to $1.925 billion (subject to certain specified reductions and offsets), plus tiered royalties on net sales of ANG-3777 at royalty rates of up to 40%. Under the Vifor License, we are responsible for executing a pre-specified clinical development plan designed to obtain regulatory approvals of ANG-3777 for DGF and CSA-AKI. For the years ended December 31, 2021 and 2020, we recognized license revenue related to the Vifor License of $27.5 million and $0.2 million, respectively. As of December 31, 2021, we recorded $2.3 million as the current portion of deferred revenue on the consolidated balance sheet related to the Vifor License. As of December 31, 2020, we recorded $29.8 million as deferred revenue on the consolidated balance sheet related to the Vifor License.
On October 26, 2021, we announced that the Phase 3 trial of ANG-3777 in DGF did not achieve its primary endpoint and the data were not expected to be sufficient evidence to support an indication in the studied DGF population. On December 14, 2021, we announced that the Phase 2 trial of ANG-3777 in CSA-AKI did not achieve its primary endpoint. The Vifor License includes additional milestone and royalty objectives related to the clinical development plan for ANG-3777 and we do not expect to receive any clinical, post-approval, or sales milestones, or royalties, as we do not intend to continue to pursue such clinical development plan for ANG-3777, which had included a Phase 3 study for CSA-AKI and a Phase 4 confirmatory study in DGF. In 2022, we and Vifor Pharma continue to work to complete the planned analyses of the results of the clinical trials announced in the fourth quarter of 2021 and to discuss the future of the collaboration based upon such analyses. As of December 31, 2021, we recorded the remaining performance obligation as current deferred revenue of $2.3 million which is expected to be completed by the end of 2022.
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Components of Results of Operations
The following discussion summarizes the key factors our management believes are necessary for an understanding of our financial statements.
Revenue
We do not have any products approved for sale and have not generated any revenue from product sales. Our revenue to date primarily has been derived from government funding consisting of U.S. government grants and contracts, and revenue under our license agreements, specifically the Vifor License.
Grant Revenue
Our grants and contracts reimburse us for direct and indirect costs relating to the grant projects and also provide us with a pre-negotiated profit margin on total direct and indirect costs of the grant award, excluding subcontractor costs, after giving effect to directly attributable costs and allowable overhead costs. Funds received from grants and contracts are generally deemed to be earned and recognized as revenue as allowable costs are incurred during the grant or contract period and the right to payment is realized.
Contract Revenue
Our license agreements comprise elements of upfront license fees, milestone payments based on development and royalties based on net product sales. The timing of our operating cash flows may vary significantly from the recognition of the related revenue. Income from upfront payments is recognized when we satisfy the performance obligations in the contract, which can result in recognition at either a point in time or over the period of continued involvement. Other revenue, such as milestone payments, are recognized when achieved.
Our revenue to date has been generated from payments received pursuant to the Vifor License Agreement. We recognize revenue from upfront payments over the term of our estimated period of performance using a cost-based input method under Topic 606, Revenue from Contracts with Customers.
In addition to receiving an upfront payment, we may also be entitled to milestones and other contingent payments upon achieving predefined objectives. If a milestone is considered probable of being reached, and if it is probable that a significant revenue reversal would not occur, the associated milestone amount would also be included in the transaction price.
We expect that any license revenue we generate from any future collaboration partners, will fluctuate in the future as a result of the timing and amount of upfront, milestones and other collaboration agreement payments and other factors.
Operating Expenses
CostOur operating expenses since inception have consisted primarily of Grant Revenue
Our cost of grant revenue primarily relates to personnel-related costsresearch and development expenses for grant projects.and general and administrative costs.
Research and Development Expenses
To date, our research and development expenses have primarily related to discovery efforts and preclinical and clinical development of our product candidates. We recognize research and development expenses as they are incurred and payments made prior to the receipt of goods or services to be used in research and development are capitalized until the goods or services are received. Our research and development expenses consist primarily of:of costs incurred for the development of our product candidates and our drug discovery efforts, which include:
personnel costs, includingwhich include salaries, payroll taxes, employee benefits and stock-basedequity-based compensation for personnel in research and development functions;expense;
costs associated• expenses incurred under agreements with medical affairs activities;
fees paid to consultants clinical testing sites and contract research organizations (CROs), including in connection with our preclinical studies and clinical trials, and other related clinical trial fees, such as for investigator grants, patient screening, laboratory work, clinical trial database management, clinical trial material management and statistical compilation, analysis and reporting;
contractedthat conduct research and license agreement fees with no alternative future use;
development activities on our behalf;
• costs related to sponsored research service agreements;
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costs related to acquiring, manufacturingproduction of preclinical and maintaining clinical trial materials, including fees paid to contract manufacturers;
• laboratory and laboratory supplies;
depreciation of equipment and facilities;
legalvendor expenses related to the execution of preclinical studies and planned clinical trial agreementstrials; and material transfer agreements;
• laboratory supplies and equipment used for internal research and development activities.
We expense all research and development costs relatedin the periods in which they are incurred. Costs for certain research and development activities are recognized based on an evaluation of the progress to preparationcompletion of regulatory submissionsspecific tasks using information and compliance with regulatory requirements.data provided to us by our vendors and service providers.

Other than with respect to reimbursable expenses required to be recorded under our government grants and contracts, we do not allocate our expenses by product candidates. A significant amount of our directOur research and development expenses include payrollare not currently tracked on a program-by-program basis. We use our personnel and other personnel expenses for our departments that supportinfrastructure resources across multiple product candidate research and development programs directed toward identifying and other than as specified above, we do not recorddeveloping product candidates. Substantially all our research and development expenses by product. However, research and development expenses were primarily driven by expenses relating tocosts are incurred on the development of ANG-3777ELI-002 and ANG-3070 in 2021ELI-004, an AMP adjuvant that is a significant component of ELI-002, and 2020. Of our total
research and development expenses for the years ended December 31, 2021 and 2020, 62% and 73%, respectively, of such expenses were from external third-party sources and the remaining 38% and 27%, respectively, were from internal sources.preclinical candidates.
We expect our research and development expenses to be slightly lower inincrease substantially for the near term, even thoughforeseeable future as we will continue the development of our product candidates and continue to invest in research and development activities.activities related to developing our product candidates, including investments in conducting clinical trials, manufacturing and otherwise advancing our programs. The process of conducting the necessary clinical research necessary to obtain regulatory approval is costly and time consuming,time-consuming, and the successful development of our product candidates is highly uncertain. At this time, we cannot reasonably estimate the nature, timing orand costs of the efforts that will be necessaryneeded to complete the remainder of the development of, any of our clinical or preclinical product candidates or the period, if any, in which material net cash inflows may commence from these product candidates may commence.ELI-002 or any of our preclinical candidates. This is due to the numerous risks and uncertainties associated with developing drugs, including the uncertainty of:
the scope, rate of progress and expense of our ongoing, as well as any additional, clinical trials and other research and development activities;
future preclinicalclinical trials and clinical trialearly-stage results;
obtaining market accessthe terms and reimbursementtiming of regulatory approvals; and
the timingability to market, commercialize and receiptachieve market acceptance for ELI-002, or any of any regulatory approvals.
A changeour preclinical candidates that we or our future collaboration partners may develop in the outcome of anyfuture.
Any of these variables with respect to the development of a product candidateELI-002, or any other of our preclinical candidates that we may develop could meanresult in a significant change in the costs and timing associated with the development of that product candidate.such candidates. For example, if the FDA or anotherother regulatory authority were to require us to conduct preclinical orand clinical trialsstudies beyond those thatwhich we currently anticipate will be required for the completion of clinical development of a product candidate, or if we experience significant delays in enrollment in any of our preclinical or clinical trials, we could be required to expend significant additional financial resources and time on the completion of our clinical development programs.
General and Administrative Expenses
GeneralOur general and administrative expenses consist primarily of personnel-relatedpersonnel costs, including equity-based compensation, and other expenses such as salaries, payroll taxes, employee benefitsfor outside professional services, including marketing, legal, audit and stock-based compensation, for personnelaccounting, facility-related costs not otherwise included in executive, operational, financeresearch and human resources functions. Other significant generaldevelopment expenses, and administrative expenses include allocation of facilities costs, accounting and legal services and expenses associated with obtaining and maintaining patents. A portion of the general and administrative expenses are reimbursed through the overhead rates contained in our grants with the U.S. Government.
recruiting. We expect that our general and administrative expenses to be generally consistent inincrease over the near termnext several years to support our continued research and development activities. We also expect to generally maintainactivities, manufacturing activities, increased costs of expanding our current level of expenses associated withoperations and operating as a public company, including expensescompany. These increases will likely include increases related to audit,the hiring of additional personnel and legal, regulatory and tax-relatedother fees and services associated with maintaining compliance with Nasdaq Stock Market LLC (“Nasdaq”), Marketplace Rules, or the rulesNasdaq Listing Rules and regulations of the SECSecurities and standards applicable to companies listed on a national securities exchange,Exchange Commission (“SEC”) requirements, accounting and audit fees, director and officer insurance expenses,costs and investor relations activities and other administrative and professional services.
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costs associated with being a public company.
Other Income (Expense)
Convertible Notes Recorded at Fair Value
We electedFor the fair value option for recognitionyears ended December 31, 2023 and 2022, other income and expense consisted primarily of our convertible notes. Our convertible notes were subject to re-measurement each reporting period with gains andinterest income, foreign exchange transaction losses, reported through our consolidated statementsloss on sale of operations. All of our convertible notes were converted into shares of our common stock upon the closing of our initial public offering.
Liability Classified Series C Convertible Preferred Stock Recorded at Fair Value
Series C convertible preferred stock includes settlement features that resultequipment, interest expense, changes in liability classification. The initial carrying value of the Series C convertible preferred stock was accreted to the settlement value, the fair value of the securities to be issued upon the conversionembedded derivative, gain on extinguishment of the Series C Preferred Stock. The discount to the settlement value was accreted to interest expense using the effective interest method. During 2020, certain of the convertiblepromissory notes, were exchanged for Series C convertible preferred stock. As the exchange was accounted for as a modification, the Series C convertible preferred stock that was exchanged for the convertible notes (the Exchanged Series C Shares) continued to be recorded at fair value. The Exchanged Series C Shares were subject to re-measurement each reporting withand gains and losses reported through our consolidated statements of operations. All sharesrelated to the re-measurement of our Series C convertible preferred stock converted into common stock in connection with the IPO.warrant liabilities.
Warrant Liability
We have accounted for certain of our freestanding warrants to purchase shares of our common stock as liabilities measured at fair value, in accordance with ASC 815, Derivatives and Hedging (ASC 815). The warrants are subject to re-measurement at each reporting period with gains and losses reported through our consolidated statements of operations.
Foreign Exchange Transaction Gain
Foreign currency transaction gains, primarily related to intercompany loans, are recorded as a component of other income (expense) in our consolidated statements of operations.
Earnings in Equity Method Investment
Earnings in equity method investment represents our 10% interest in NovaPark that is accounted for under the equity method.
Interest Income
Interest income consists of interest earned on our cash and cash equivalents.
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Results of Operations
Comparison for the Years Ended December 31, 20212023 and 20202022
The following table summarizes our results of operations for the periods indicated:
Year Ended December 31,
20212020$ Change% Change
(In thousands, except percentages)
Revenue:
Contract revenue$27,506 $193 $27,313 *
Grant revenue806 2,687 (1,881)(70.0)%
Total revenue28,312 2,880 25,432 883.1 %
Year Ended December 31,
2023
2023
20232022$ Change% Change
(In thousands, except percentages)(In thousands, except percentages)
Operating expenses:Operating expenses:
Cost of grant revenue433 1,190 (757)(63.6)%
Research and development
Research and development
Research and developmentResearch and development48,698 38,977 9,721 24.9 %$23,849 $$18,103 $$5,746 31.7 31.7 %
General and administrativeGeneral and administrative18,488 17,986 502 2.8 %General and administrative11,896 5,630 5,630 6,266 6,266 111.3 111.3 %
Total operating expensesTotal operating expenses67,619 58,153 9,466 16.3 %Total operating expenses35,745 23,733 23,733 12,012 12,012 50.6 50.6 %
Loss from operationsLoss from operations(39,307)(55,273)15,966 (28.9)%Loss from operations(35,745)(23,733)(23,733)(12,012)(12,012)50.6 50.6 %
Other income (expense), netOther income (expense), net(15,266)(24,834)9,568 *Other income (expense), net550 (4,475)(4,475)5,025 5,025 (112.3)(112.3)%
Net lossNet loss$(54,573)$(80,107)$25,534 (31.9)%Net loss$(35,195)$$(28,208)$$(6,987)24.8 24.8 %
_______________________
*Not meaningful
Contract Revenue
Contract revenue increased by $27.3 million, from the year ended December 31, 2020 to the year ended December 31, 2021. The increase is attributable to revenue recognized related to the upfront payment from Vifor Pharma pursuant to the Vifor License Agreement entered into in 2020. As of December 31, 2021, we have substantially satisfied the performance obligation under the Agreement which caused an acceleration of the deferred revenue. We do not expect to receive any further substantial revenues under the Vifor License Agreement and we expect the remaining unearned revenue under the Vifor License Agreement to be recognized by the end of 2022.
Grant Revenue
Grant revenue decreased by $1.9 million, or 70.0%, from the year ended December 31, 2020 to the year ended December 31, 2021. The decrease is primarily attributable to a decrease in reimbursable costs relating to our grant from the U.S. Department of Defense for the year ended December 31, 2021. We do not expect to receive any further substantial grant revenues for the foreseeable future.

Cost of Grant Revenue
Cost of grant revenue decreased by $0.8 million, or 63.6%, from the year ended December 31, 2020 to the year ended December 31, 2021. The decrease is primarily attributable to a decrease in personnel-related costs and expenses applied for the year ended December 31, 2021.
Research and Development Expenses
Research and development expenses increased by $9.7$5.7 million, or 24.9%31.7%, fromfor the year ended December 31, 20202023 compared to the year ended December 31, 2021.2022. The net increase in research and development expenses was primarily due to an increase of $8.5 million in personnel-related expenses, including salaries, benefitsexternal costs associated with ELI-002 manufacturing and stock-based compensation expenses, as a result from increases in headcount and an increase of $1.0 million in CRO and CMO expenses from increased clinical and non-clinical trial activities, primarily related to the development of ANG-3777 and ANG-3070. These increases were partially offset by an employee retention credit of $1.2 million received in 2021 as a reduction to payroll taxes.
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trials.
General and Administrative Expenses
General and administrative expenses increased by $0.5$6.3 million, or 2.8%111.3%, fromfor the year ended December 31, 20202023 compared to the year ended December 31, 2021.2022. The increase in general and administrative expenses was primarily due to an increasehigher personnel-related costs in support of $2.5 million of personnel-related expenses, including salaries, benefitsorganizational growth and stock-based compensation expenses, resulting from increases in headcount and vesting of performance-based stock units upon IPO, and an increase of $2.7 million of corporate fees mainly due to purchase of business insurance, offset by a reduction of $5.1 million ofhigher professional fees for legal, consulting, accounting, taxincurred in connection with the Merger and other services primarily associated with preparing us for our IPO in 2020.operating as a public company.
Other Income (Expense), Net
Other income (expense), net changedincreased by a reduction in expense of $9.6$5.0 million fromfor the year ended December 31, 20202023 compared to the year ended December 31, 2021. This decrease in expense is2022. The increase was primarily attributabledue to a reduction inreduced interest expense of $7.0 million due to interest associated with convertible notes and Series C convertible preferred stock in 2020 that were converted into equity upon our IPO in February 2021 and an increase of $2.6 million in fair value of our warrant liability, convertible notes, and Series C convertible preferred stock for which we have elected the fair value option. The convertible notes and warrants both require re-measurement at each balance sheet date with gains and losses reported through our consolidated statement of operations.promissory notes.
Liquidity and Capital Resources
Sources and Uses of Liquidity
WeOur operations through December 31, 2023 have incurred losses and negative cash flows from operations since inception, and we anticipate that we will incur losses for at least the next several years. To date, we have not generated any revenue from product sales. We have funded our operationsbeen financed primarily through the receipt of grants, the sale of debt and equity securities, and proceeds from license agreements. In February 2021, we generatedby aggregate net proceeds of approximately $107.0$106.6 million from our IPOthe issuance of common stock, convertible preferred stock, convertible notes, the exercise of stock options and Concurrent Private Placement, after deductingcommon stock warrants and proceeds from the underwriting discountsMerger. Since inception, we have had significant operating losses. Our net loss was $35.2 million and commissions.$28.2 million for the years ended December 31, 2023 and 2022, respectively. As of December 31, 2021,2023, we had $88.8 million of cash and cash equivalents and an accumulated deficit of $215.1 million.
Prior to our IPO, we issued $36.2$142.2 million and $12.9 million in aggregate principalcash and cash equivalents. Our primary use of cash is to fund operating expenses, which consist primarily of research and development expenditures, and to a lesser extent, general and administrative expenditures. Cash used to fund operating expenses is impacted by the timing of when we pay these expenses, as reflected in the change in our outstanding accounts payable and accrued expenses.
Our losses from operations, negative operating cash flows and accumulated deficit, as well as the additional capital needed to fund operations for at least twelve months following the issuance of the consolidated financial statements, raise substantial doubt about our ability to continue as a going concern. We expect to incur substantial expenditures in the foreseeable future for the development of our product candidates and will require additional financing to continue this development. The consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K have been prepared on a basis that assumes that we will continue as a going concern, which contemplates the realization of assets and satisfaction of liabilities in the normal course of business. The consolidated financial statements do not include any adjustments relating to the recoverability and classification of recorded asset amounts or the amounts and classification of liabilities that might be necessary should we be unable to continue as a going concern. We plan to address this condition through the sale of common stock in public
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offerings and/or private placements, debt financings, or through other capital sources, including licensing arrangements, partnerships and collaborations with other companies or other strategic transactions. However, there is no assurance that we will be successful in raising additional capital or that such additional funds will be available on acceptable terms, if at all. Should we be unable to raise this amount of convertiblecapital our operating plans will be limited to the amount of capital that we can access. We may also consider steps to reduce our operating expenses. There can be no assurances that we will be successful in any of the foregoing.
Summary Statement of Cash Flows
The following table sets forth a summary of our net cash flow activity for the years ended December 31, 2023 and 2022 (in thousands):
Year Ended December 31,
20232022
Net cash provided by (used in)
Operating activities$(32,694)$(22,179)
Investing activities(32)(654)
Financing activities38,613 21,202 
Effect of foreign currency on cash— — 
Net (decrease) increase in cash$5,887 $(1,631)
Operating activities
For the year ended December 31, 2023, net cash used in operating activities was $32.7 million, which primarily consisted of a net loss of $35.2 million and the change in net operating assets and liabilities of $0.1 million partially offset by the net non-cash charges of $2.6 million. The change in net operating assets and liabilities of $0.1 million was the result of a $0.7 million decrease in the deferred research obligation, $0.8 million decrease in prepaid assets, and $0.8 million decrease in the operating lease liability offset by an increase in accounts payable and accrued expenses of $2.2 million. The $2.6 million of net non-cash charges were related to $1.1 million of interest expense related to the accretion of promissory notes payable, $1.2 million of stock-based compensation, $0.8 million related to various investorsthe amortization of the right-of-use asset, $0.4 million of depreciation, $0.1 million loss on disposal of property and we also issued 34,928 sharesequipment partially offset by $0.4 million increase in the fair value of the embedded derivative associated with the promissory notes payable and $0.6 million of gain on the extinguishment of the promissory notes payable.
For the year ended December 31, 2022, net cash used in operating activities was $22.2 million, which primarily consisted of a net loss of $28.2 million and a change in net operating assets and liabilities of $0.2 million, partially offset by net non-cash charges of $6.2 million. The change in net operating assets and liabilities of $0.2 million was the result of a $1.8 million decrease in prepaid assets and a $0.5 million decrease in the operating lease liability offset by an increase in accounts payable and accrued expenses of $0.8 million, and an increase of the deferred research obligation of $1.4 million. The net non-cash charges of $6.2 million were primarily related to $3.6 million of non-cash interest expense, $0.9 million of non-cash change in the fair value of the embedded derivative, $0.4 million of depreciation expense, $0.7 million related to amortization of the right-of-use asset associated with our operating leases and $0.6 million of stock-based compensation expense.
Investing activities
For the year ended December 31, 2023, an immaterial amount of cash was provided or used in investing activities, and for the year ended December 31, 2022, net cash used in investing activities was $0.7 million, primarily used to purchase capital equipment.
Financing activities
For the year ended December 31, 2023, net cash provided by financing activities was $38.6 million, comprised of $31.6 million of net proceeds from the Merger and $7.0 million of proceeds from the sale of common stock. For the year ended December 31, 2022, net cash provided by financing activities was $21.2 million, comprised of $21.1 million of net proceeds from the issuance of Series C convertible preferred stock at $642.75 per share for grossand $0.1 million of proceeds from the exercise of approximately $22.3 million. Upon the closing of our IPO, all then outstanding convertible notes and shares of convertible preferredcommon stock were converted into 5,870,829 shares of our common stock.
In April 2020, we were approved for and received a loan of approximately $0.9 million from Hanmi Bank under the Coronavirus Aid, Relief and Economic Security Act (the CARES Act) and the Paycheck Protection Program (PPP) offered by the U.S. Small Business Administration (SBA). The loan was evidenced by a promissory note and agreement, dated April 21, 2020 (the PPP Note). The PPP Note proceeds were available to be used to pay for payroll costs, including salaries, commissions, and similar compensation, group health care benefits, and paid leaves; rent; utilities; and interest on certain other outstanding debt, if any. The interest rate on the PPP Note was a fixed rate of 1% per annum. The SBA approved our PPP Loan forgiveness application on May 26, 2021 for the entire principal amount of the PPP Loan and accrued interest.

options.
Future Cash Needs and Funding Requirements

Based on our current operating plan, we believe that our cash and cash equivalents will be sufficient to fund our planned operations for at least 12 months, well into 2023, following the issuance datethird quarter of our consolidated financial statements.2024. However, we have based our projections of operating capital requirements on assumptions that may prove to be incorrect and we may use all our available capital resources
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sooner than we expect. Because of the numerous risks and uncertainties associated with research, development and commercialization of biotechnology products, weWe are unable to estimate the exact amount of our operating capital requirements. The amount and timing of our future funding requirements will depend on many factors, including, but not limited to:
the scope, progress, results and costs of researching and developing ANG-3070 or any other product candidates, and conducting preclinical studies and clinical trials;
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the outcome of our ongoing andany future clinical trials, including our Phase 2 clinical trial of ANG-3070 in patients with PPKD;for any existing or future product candidates;
whether we are able to take advantage of any FDA expedited development and approval programs for any of our product candidates;
the extent to which COVID-19 may impact our business, including our clinical trials and financial condition;
the willingness of the FDA and foreign regulatory authorities to accept the results of our completed, ongoing, and planned clinical trials and preclinical studies and other work, as the basis for review and approval of ANG-3070;
the outcome, costs and timing of seeking and obtaining and maintaining FDA and any foreign regulatory approvals;
the costs associated with any delays we may encounter as a result of evolving regulatory requirements or adverse results with respect to any of our product candidates;
the number and characteristics of product candidates that we pursue, including our product candidates in preclinical development;
the ability of our product candidates to progress through clinical development successfully;
our need to expand our research and development activities, including to conduct additional clinical trials;
market acceptance of our product candidates, including physician adoption, market access, pricing and reimbursement;
the costs of acquiring, licensing or investing in businesses, products, product candidates and technologies;
our ability to maintain, expand and defend the scope of our intellectual property portfolio, including the amount and timing of any payments we may bepotentially required to make, or that we may receive, in connection with the licensing, filing, prosecution, defense and enforcement of any patents or other intellectual property rights;
our need and ability to hire additional personnel, including management, clinical development, medical and commercial personnel;
the effect of competing technological, market developments and government policy;
the costs associated with being a public company, including our need to implement additional internal systems and infrastructure, including financial and reporting systems;
the costs associated with securing and establishing commercialization and manufacturing capabilities, as well as those associated with packaging, warehousing and distribution;
the costs associated with being a commercial company with approved products for sale, including our obligation to meet applicable healthcare laws and regulations and implement robust compliance programs;
the economic and other terms, timing of and success of our existing licensing arrangements and any collaboration, licensing or other arrangements into which we may enter in the future and timing and amount of payments thereunder; and
the timing, receipt and amount of sales and general commercial success of any future approved products, if any.
Until such time as we or our collaborators can generate significant revenue from sales of ANG-3070 or any other product candidate,candidates, if ever, we expect to finance our operations through the sale of common stock in public offerings and/or private equity offerings orplacements, debt financings, or through other capital sources, of capital, including licensing arrangements, partnerships and collaborations licenses, creditwith other companies or loan facilities, receipt of research contributions or grants, tax credit revenue or a combination of one or more of these funding sources.other strategic transactions. Adequate funding may not be available to us on acceptable terms, or at all. To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our stockholders will be or could be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our common stockholders. Debt financing and equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we raise funds through additional collaborations, or other similar arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us and/or may reduce the value of our common stock. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or commercialization efforts or grant rights to develop and market our product candidates even if we would otherwise prefer to develop and market such product candidates ourselves.
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Summary Statement of Cash Flows
The following table sets forth a summary of our net cash flow activity for the years ended December 31, 2021 and 2020 (in thousands):
Year Ended December 31,
20212020
Net cash provided by (used in)
Operating activities$(52,643)$(22,888)
Investing activities(382)(41)
Financing activities107,171 52,409 
Effect of foreign currency on cash(444)
Net increase in cash$54,149 $29,036 
Operating activities
For the year ended December 31, 2021, net cash used in operating activities was $52.6 million, which primarily consisted of a net loss of $54.6 million and a change in net operating assets and liabilities of $26.0 million, partially offset by net non-cash charges of $27.8 million. The net non-cash charges were primarily related to a $14.0 million change in fair value of convertible notes, Series C convertible preferred stock and warrant liabilities, amortization of debt issuance costs of $1.9 million, and stock-based compensation expense of $12.0 million, partially offset by a gain of $0.9 million from the forgiveness of our PPP loan. The change in net operating assets and liabilities was due to a decrease of $27.5 million in deferred revenue due to substantial satisfaction of our performance obligation under the Vifor License Agreement, a decrease of $0.9 million in accounts payable and accrued expenses due to timing of invoices and an increase of $0.8 million in grants receivable due to the recognition of the qualified Australian tax credit, partially offset by a decrease of $4.0 million in prepaid expenses and other current assets, primarily due to the subsequent receipt of $5.0 million convertible note receivable under Vifor License Agreement in 2021.
For the year ended December 31, 2020, net cash used in operating activities was $22.9 million, which primarily consisted of a net loss of $80.1 million, partially offset by net non-cash charges of $31.5 million and a change in net operating assets and liabilities of $25.8 million. The net non-cash charges were primarily related to a $16.5 million change in fair value of convertible notes, Series C convertible preferred stock and warrant liabilities, amortization of debt issuance costs of $7.7 million, stock-based compensation expense of $4.7 million and placement agent fees of $1.7 million. The change in net operating assets and liabilities was due to an increase of $29.8 million in deferred revenue due to the upfront fee from the Vifor License Agreement and $3.7 million in accrued expenses due to increased clinical-related activities, partially offset by an increase of $2.0 million in prepaid expenses and other current assets and a decrease of $5.6 million in accounts payable due to our overall growth, increased research and development spending and timing of payments.
Investing activities
For the years ended December 31, 2021 and 2020, net cash used in investing activities of $0.4 million and $41,000, respectively, was primarily used to purchase of fixed assets for research activities.
Financing activities
For the year ended December 31, 2021, net cash provided by financing activities was $107.2 million, primarily due to net proceeds of $107.5 million from the IPO and Concurrent Private Placement, $1.8 million from the exercise of warrants and stock options, and $0.3 million from a sale and leaseback arrangement, partially offset by taxes paid related to net share settlement upon vesting of restricted stock awards of $2.5 million.
For the year ended December 31, 2020, net cash provided by financing activities was $52.4 million, primarily due to net proceeds of $31.2 million from the issuance of convertible notes and warrants, $20.0 million from the issuance of liability classified Series C convertible preferred stock net of issuance costs and $0.9 million in proceeds from our PPP loan.

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Critical Accounting Policies and Significant Judgments and Estimates
Our management’s discussion and analysis of our financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with U.S. generally accepted accounting principles (“GAAP”). The preparation of these consolidated financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the consolidated financial statements, as well as the reported expenses incurred during the reporting periods. Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. We believe that the accounting policies discussed below are critical to understanding our historical and future performance, as these policies relate to the more significant areas involving management’s judgments and estimates.
Going Concern
Our evaluation of our ability to continue as a going concern requires us to evaluate our future sources and uses of cash sufficient to fund our currently expected operations in conducting research and development activities one year from the date our audited consolidated financial statements are issued. We evaluate the probability associated with each source and use of cash resources in making our going concern determination. The research and development of pharmaceutical products is inherently subject to uncertainty.
Research and Development Costs
We will incur substantial expenses associated with manufacturing and clinical trials. Accounting for clinical trials relating to activities performed by contract research organizations (“CROs”) and other external vendors requires management to exercise significant estimates in regard to the timing and accounting for these expenses. We estimate costs of research and development activities conducted by service providers, which include the conduct of sponsored research, preclinical studies and contract manufacturing activities. The diverse nature of services being provided under CROs and other arrangements, the different compensation arrangements that exist for each type of service and the lack of timely information related to certain clinical activities complicates the estimation of accruals for services rendered by CROs and other vendors in connection with clinical trials. We record the estimated costs of research and development activities based upon the estimated amount of services provided but not yet invoiced and include these costs in the accrued expenses or prepaid expenses on the balance sheets and within research and development expense on the consolidated statements of operations and comprehensive loss. In estimating the duration of a clinical study, we evaluate the start-up, treatment and wrap-up periods, compensation arrangements and services rendered attributable to each clinical trial and fluctuations are regularly tested against payment plans and trial completion assumptions.
We estimate these costs based on factors such as estimates of the work completed and budget provided and in accordance with agreements established with our collaboration partners and third-party service providers. We make significant judgments and estimates in determining the accrued liabilities and prepaid expense balances in each reporting period. As actual costs become known, we adjust our accrued liabilities or prepaid expenses. We have not experienced any material differences between accrued costs and actual costs incurred since our inception.
Our expenses related to clinical trials will be based on estimates of patient enrollment and related expenses at clinical investigator sites as well as estimates for the services received and efforts expended pursuant to contracts with multiple research institutions and CROs that may be used to conduct and manage clinical trials on our behalf. We will accrue expenses related to clinical trials based on contracted amounts applied to the level of patient enrollment and activity. If timelines or contracts are modified based upon changes in the clinical trial protocol or scope of work to be performed, we will modify our estimates of accrued expenses accordingly on a prospective basis.
Leases
ASU No. 2016-02, Leases (ASC 842) establishes a right-of-use model (“ROU”) that requires a lessee to recognize a ROU asset and corresponding lease liability on the balance sheet for all leases with a term longer than 12 months. Leases will be classified as finance or operating, with classification affecting the pattern and classification of expense recognition in the consolidated statements of operations and comprehensive loss as well as the reduction of the right of use asset.
At the inception of an arrangement, we determine whether the arrangement is or contains a lease based on specific facts and circumstances, the existence of an identified asset(s), if any, and our control over the use of the identified asset(s), if applicable. Operating lease liabilities and their corresponding ROU assets are recorded based on the present value of future lease payments over the expected lease term. The interest rate implicit in lease contracts is typically not readily determinable. As such, we will utilize the incremental borrowing rate, which is the
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rate incurred to borrow on a collateralized basis over a similar term an amount equal to the lease payments in a similar economic environment.
We have elected to combine lease and non-lease components as a single component. Operating leases are recognized on the consolidated balance sheet as ROU lease assets, current lease liabilities and non-current lease liabilities. Fixed rents are included in the calculation of the lease balances, while variable costs paid for certain operating and pass-through costs are excluded. Lease expense is recognized over the expected term on a straight-line basis.
Stock-based Compensation
Prior to the Merger, we issued equity-based compensation awards through the granting of options, which generally vest over four years. We account for equity-based compensation in accordance with Accounting Standards Codification 718, Compensation - Stock Compensation (“ASC 718”). In accordance with ASC 718, compensation cost is measured at estimated fair value at grant date and is included as compensation expense over the vesting period during which service is provided in exchange for the award. Compensation cost of awards that contain a performance condition are recognized when success is considered probable during the performance period.
We use the Black-Scholes option pricing model (“Black-Scholes”) to determine fair value of our options. Black-Scholes includes various assumptions, including the fair value of common shares, expected life of incentive shares, the expected volatility, expected dividend yield, and the expected risk-free interest rate. These assumptions reflect our best estimates, but they involve inherent uncertainties based on market conditions generally outside our control. As a result, if other assumptions had been used, equity-based compensation cost could have been materially impacted. Furthermore, if we use different assumptions for future grants, equity-based compensation cost could be materially impacted in future periods.
The risk-free interest rate is estimated using the weighted average rate of return on U.S. Treasury notes with a life that approximates the expected life of the option. The expected term of options granted to employees was calculated using the simplified method, which represents the average of the contractual term of the option and the weighted-average vesting period of the option. We use the simplified method because we do not have sufficient historical option exercise data to provide a reasonable basis upon which to estimate expected term. The contractual life of the option was used for the expected life of options granted to non-employees. Expected volatility is based on the weighted average of the historical volatility of a peer group of publicly traded companies. The assumed dividend yield is based upon our expectation of not paying dividends in the foreseeable future.
We will continue to use judgment in evaluating the assumptions utilized for our equity-based compensation expense calculations on a prospective basis. In addition to the assumptions used in the Black-Scholes model, the amount of equity-based compensation expense we recognize in our consolidated financial statements includes incentive share forfeitures as they occurred.
Subsequent to the effective date of the Merger, we determine the fair value of our common stock based on the closing price of our common stock as reported by Nasdaq on the date of grant.
Derivative Financial Instruments
The convertible notes include an embedded derivative requiring bifurcation in accordance with Accounting Standards Codification (“ASC”) 815, Derivatives and Hedging. The valuation of this instrument is determined using widely accepted valuation technique including the probability weighted expected return model. The fair value was determined using a model with the assumptions for equity value proceeds, probability of occurrence of various liquidation scenarios, timeline to liquidity and risk-free interest rate. The fair value of this derivative instrument is measured at each reporting period with changes in fair value reported in earnings. On October 18, 2022, in conjunction with the shares of Series C preferred stock issued on this same date, the convertible notes payable totaling $14.5 million and the related accrued interest totaling $1.1 million automatically converted into 1,370,187 shares of Series C preferred stock at an 80% discount to the Series C preferred stock issuance price per share of $14.23, or $11.39 per share. Just prior to settlement, the fair value of the embedded derivative was marked to market a final time to the aggregate value of $3.9 million. We recorded an immaterial gain on extinguishment related to the difference in the total of convertible notes payable, total accrued interest and the final fair value of the embedded derivative versus the value of the Series C preferred stock shares issued based on the original issuance price of $14.23 per share.
Contractual Obligations and Other Commitments
The following table summarizes our contractual obligations as of December 31, 2021 (in thousands):
For the Year Ended Payments due by period
(in thousands)Less than 1 year1 to 3 years3 to 5 yearsMore than 5 yearsTotal
Operating lease obligations$1,289 $3,618 $516 $— $5,423 
Financing obligations$94 $219 $— $— $313 
2023:

Critical Accounting Policies and Significant Judgments and Estimates
A description of recently issued accounting pronouncements that may potentially impact our financial position and results of operations is disclosed in Note 2 to our consolidated financial statements appearing elsewhere in this Annual Report.
The critical accounting policies requiring estimates, assumptions, and judgments that we believe have the most significant impact on our consolidated financial statements are described below.
Contract Revenue
We account for revenue earned from contracts with customers under Accounting Standards Update ("ASU") No. 2014-09, Revenue from Contracts with Customers (Topic 606) ("ASC 606"). Under ASC 606, we recognize revenue when a customer obtains control of promised goods or services, in an amount that reflects the consideration we expect to receive in exchange for those goods or services. To determine revenue recognition for arrangements within the scope of ASC 606, we perform the following five steps:     
(1)    Identify the contract(s) with a customer;
(2)    Identify the performance obligations in the contract;
(3)    Determine the transaction price;
(4)    Allocate the transaction price to the performance obligations in the contract; and
(5)    Recognize revenue when (or as) we satisfy a performance obligation.
At contract inception, we assess the goods or services promised within each contract, whether each promised good or service is distinct, and determine those that are performance obligations. We then recognize as revenue the amount of the transaction price that is allocated to the respective performance obligation when or as the performance obligation is satisfied.
We enter into agreements under which it may obtain upfront payments, milestone payments, royalty payments and other fees. Promises under these arrangements may include licenses of intellectual property, research services, including selection campaign research services for certain replacement targets, the obligation to share information during the research and the participation of alliance managers and in joint research committees, joint patent committees and joint steering committees. We assess these promises within the context of the agreements to determine the performance obligations.
Licenses of Intellectual Property: If a license to our intellectual property is determined to be distinct from the other promises or performance obligations identified in the arrangement, we recognize revenue from non-refundable, upfront fees allocated to the license when the license is transferred to the customer and the customer is able to use and benefit from the license. For licenses that are bundled with other promises, we utilize judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, the appropriate method of measuring proportional performance for purposes of recognizing revenue from non-refundable, upfront payments. We evaluate the measure of proportional performance each reporting period and, if necessary, adjust the measure of performance and related revenue recognition.
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Payments due by period
(in thousands)TotalLess than one yearOne to two yearsThree to four yearsFive and more years
Leases$8,817 $1,427 $1,350 $2,808 $3,232 
Milestone payments
:
We evaluate whetherenter into contracts in the regulatorynormal course of business with third-party service providers for clinical trials, preclinical research studies and development milestonestesting, manufacturing and other services and products for operating purposes. We have not included our payment obligations under these contracts in the table as these contracts generally provide for termination upon notice, and therefore, we believe that our non-cancelable obligations under these agreements are considered probable of being reachednot material and we cannot reasonably estimate the amounts to be included in the transaction price using the most likely amount method. We evaluate factors such as the scientific, clinical, regulatory, commercial and other risks that must be overcome to achieve the particular milestone in making this assessment. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price. At the endtiming of each reporting period, we re-evaluate the probability of achievement of milestones and any related constraint, and if necessary, adjusts the estimate of the overall transaction price.
Sales-based milestones and royalties: For sales-based royalties, including milestone payments based on the level of sales, we determine whether the sole or predominant item to which the royalties relate is a license. When the license is the sole or predominant item to which the sales-based royalty relates, we recognize revenue at the later of: (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied). To date, we have not recognized any sales-based royalty revenue resulting from any license agreement.
Deferred revenue, which is a contract liability, represents amounts received by us for which the related revenues have not been recognized because one or more of the revenue recognition criteria have not been met. The current portion of deferred revenue represents the amount expected to be recognized within one year from the consolidated balance sheet date based on the estimated performance period of the underlying performance obligation. The noncurrent portion of deferred revenue represents amounts expected to be recognized after one year through the end of the performance period of the performance obligation.
Using the cost-based input method, we recognize revenue based on actual costs incurred as a percentage of total estimated costs as we complete each performance obligation. As such, we use significant assumptions to determine the total estimated costs for us to complete the performance obligation identified under the Vifor License Agreement as well as the performance period. We reassess the total estimated costs and performance period at each reporting period. We changed the estimated costs significantly from $231.5 million at inception (November 2020) to $26.0 million as of December 31, 2021 and revised the performance period from 9.5 years to 2.2 years due to new information available at each reporting period. As of December 31, 2021, we determined we have substantially completed our performance obligation under the Vifor License Agreement. The effect of this change in estimate was an increase in contract revenue by $24.2 million, a reduction in net loss by $24.2 million and an increase in basic and diluted earnings per share by $0.86 for the year ended December 31, 2021. See Note 3 in this Annual Report on Form 10-K for more information.
Grant Revenue
We concluded that our government grants are not within the scope of ASC 606 as they do not meet the definition of a contract with a customer. We have concluded that the grants meet the definition of a contribution and are non-reciprocal transactions, and have also concluded that Subtopic 958-605, Not-for-Profit-Entities-Revenue Recognition, does not apply, as we are a business entity and the grants are with governmental agencies.
In the absence of applicable guidance under GAAP, we developed a policy for the recognition of grant revenue when the allowable costs are incurred and the right to payment is realized.
We believe this policy is consistent with the overarching premise in ASC 606, to ensure that revenue recognition reflects the transfer of promised goods or services to customers in an amount that reflects the consideration that we expect to be entitled to in exchange for those goods or services, even though there is no exchange as defined in ASC 606. We believe the recognition of revenue as costs are incurred and amounts become realizable is analogous to the concept of transfer of control of a service over time under ASC 606.
Research and Development
Research and development costs include, but are not limited to, payroll and personnel expenses, laboratory supplies, preclinical studies, compound manufacturing costs, consulting costs and allocated overhead, including rent, equipment, depreciation and utilities. Research and development cost may be offset by research and development refundable tax rebates received by our wholly-owned Australian subsidiary.
We have agreements with various Contract Research Organizations ("CROs") and third-party vendors. We estimate research and development accruals of amounts due to the CRO based on the level of services performed, progress of the studies, including the phase or completion of events, and contracted costs. We include the
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estimated costs of research and development provided, but not yet invoiced, in accrued liabilities on the consolidated balance sheet. We record payments made to CROs under this arrangement in advance of the performance of the related services as prepaid expenses and other current assets until the services are rendered. We make judgments and estimates in determining the accrued liabilities balance in each reporting period. As actual costs become known, we adjust our accrued liabilities. For the years ended December 31, 2021 and 2020, we have not experienced any material differences between accrued costs and actual costs incurred.
Stock-Based Compensation
We account for all stock-based payments to employees and non-employees, including grants of stock options, restricted stock awards ("RSAs"), restricted stock units ("RSUs"), including restricted stock units with non-market performance and service conditions ("PSUs") to be recognized in the financial statements, based on their respective grant date fair values. We estimate the fair value of stock option grants using the Black-Scholes option pricing model. We value the RSAs, RSUs and PSUs based on the fair value of our common stock on the date of grant. The assumptions used in calculating the fair value of stock-based awards represent management's best estimates and involve inherent uncertainties and the application of management's judgment. We record expense for stock-based compensation related to stock options, RSAs and RSUs over the requisite service period. As the PSUs have a performance condition, we recognize compensation expense for each vesting tranche over the respective requisite service period of each tranche if and when our management deems probable that the performance conditionsthey will be satisfied.occur. We may recognize a cumulative true-up adjustment related to PSUs once a condition becomes probable of being satisfied if the related service period had commenced in a prior period. We record all stock-based compensation costs in generalcould also enter into additional research, manufacturing, supplier and administrative or research and development costsother agreements in the consolidated statementsfuture, which may require up-front payments and even long-term commitments of operations based upon the respective employee or non-employee's roles within our company. We record forfeitures as they occur.cash.
See Note 9 in this Annual ReportIn January 2016, we licensed certain intellectual property from MIT on Form 10-K for more information concerning certain of the specific assumptions we used in applying the Black-Scholes option pricing model to determine the estimated fair value of our stock options. Certain of such assumptions involve inherent uncertainties and the application of significant judgment. As a result, if factors or expected outcomes change and we use significantly different assumptions or estimates, our stock-based compensation could be materially different.
Warrant Liability
We account for certain common stock warrants outstanding as a liability, in accordance with ASC 815, at fair value and adjust the instruments to fair value at each reporting period. This liability is subject to re-measurement at each reporting period until exercised, and we recognize any change in fair value in the consolidated statements of operations as a component of other income (expense). We have estimated the fair value of the warrants issued by us using a variant of the Black Scholes option pricing model. We valued the underlying equity included in the Black Scholes option pricing model based on the equity value implied from sales of preferred and common stock.
Income Taxes
We record income taxes in accordance with ASC 740, Income Taxes (ASC 740), which provides for deferred taxes using an asset and liability approach. We recognize deferred tax assets and liabilities for the expected future tax consequences of eventsterms that have been includedamended from time to time. The license term extends until terminated by either party under certain provisions. We are required to pay certain contractual maintenance and milestone payments related to clinical trials and royalties on product sales over the term of the contract, with minimum annual royalty payments commencing in the consolidated financial statements or tax returns. We determine deferred tax assets and liabilities based on the difference between the financial statement and tax bases of assets and liabilities using enacted tax rates in effect for thecalendar year in which we expect the differences to reverse. We provide valuation allowances if, based upon the weight of available evidence, it is more likely than not that some or all of the deferred tax assets will not be realized.
We account for uncertain tax positions in accordance with the provisions of ASC 740. When uncertain tax positions exist, we recognize the tax benefit of tax positions to the extent that the benefit would more likely than not be realized assuming examination by the taxing authority. The determination as to whether the tax benefit will more likely than not be realized is based upon the technical merits of the tax position as well as consideration of the available facts and circumstances. To date, there have been no interest or penalties charged in relation to the unrecognized tax benefits.

after commercialization.
Recent Accounting Pronouncements
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See Note 2, “Summary of Significant Accounting Policies” in the Notes to the Consolidated Financial Statements set forth in Item 8 of this Annual Report on Form 10-K for a full description of recent accounting standards.
Emerging Growth Company and Smaller Reporting Company Status
We are a smaller reporting company and an emerging growth company, as defined inunder the JOBS Act. Under the JOBS Act, emerging growth companies can delay the adoption of new or revised accounting standards issued subsequent to the enactment of the JOBS Act until such time as those standards apply to private companies. Other exemptions and reduced reporting requirements under the JOBS Act for emerging growth companies include presentation of only two years of audited financial statements in a registration statement for an initial public offering, an exemption from the requirement to provide an auditor's report on internal controls over financial reporting pursuant to Sarbanes-Oxley Act of 2002, as amended (Sarbanes-Oxley)(“Sarbanes-Oxley”) an exemption from any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation, and less extensive disclosure about our executive compensation arrangements. We have elected to use the extended transition period for complying with new or revised accounting standards that have different effective dates for public and private companies until the earlier of the date that (i) we are no longer an emerging growth company or (ii) we affirmatively and irrevocably opt out of the extended transition period provided in the JOBS Act. As a result, our consolidated financial statements may not be comparable to companies that comply with new or revised accounting standards as of public company effective dates.
We will remain an emerging growth company until the earliest of (i) December 31, 2026, (ii) the last day of our first fiscal year in which we have total annual gross revenue of $1.07$1.235 billion or more, (iii) the date on which we are deemed to be a "large accelerated filer," as defined in Rule 12b-2 under the Securities Exchange Act of 1934, as amended (Exchange Act)(the “Exchange Act”), which means the market value of equity securities that is held by non-affiliates exceeds $700 million as of the last business day of our most recently completed second fiscal quarter and (iv) the date on which we have issued more than $1.0 billion in non-convertible debt securities during the prior three-year period.
Even after we no longer qualify as an emerging growth company, we may still qualify as a "smaller reporting company" and/or “non-accelerated filer” which may allow us to take advantage of many of the same exemptions from disclosure requirements including not being required to comply for a period of time with the auditor attestation requirements of Section 404 of Sarbanes-Oxley, and reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements.
Item7A.Item 7A. Quantitative and Qualitative Disclosures About Market Risk
We are a smaller reporting company as defined by Rule 12b-2 of the Exchange Act and are not required to provide the information required under this item.
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Item 8. Financial Statements and Supplementary Data.

The financial statements of Angion Biomedica Corp,Elicio Therapeutics, Inc., listed below are set forth in Item 8 of this Annual Report for the years ended December 31, 20212023 and 2020:2022:
ANGION BIOMEDICA CORP.ELICIO THERAPEUTICS, INC.
INDEX TO CONSOLIDATED FINANCIAL STATEMENTS
Page
Report of Independent Registered Public Accounting Firm (Moss Adams(Baker Tilly US, LLP, Seattle, Washington,Tewksbury, Massachusetts, PCAOB ID: 659)23)
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REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
To the Stockholders and the Board of Directors and Stockholders of
Angion Biomedica Corp. Elicio Therapeutics, Inc.
Opinion on the Financial Statements
We have audited the accompanying consolidated balance sheets of Angion Biomedica Corp.Elicio Therapeutics, Inc. (the “Company”) as of December 31, 20212023 and 2020,2022, the related consolidated statements of operations and comprehensive loss, convertible preferred stock and stockholders’ equity (deficit), and cash flows, for each of the two years thenin the period ended December 31, 2023, and the related notes (collectively referred to as the “consolidated financial statements”). In our opinion, the consolidated financial statements present fairly, in all material respects, the consolidated financial position of the Company as of December 31, 20212023 and 2020,2022, and the consolidated results of its operations and its cash flows for each of the two years thenin the period ended December 31, 2023, in conformity with accounting principles generally accepted in the United States of America.
Going Concern Uncertainty
The accompanying consolidated financial statements have been prepared assuming that the Company will continue as a going concern. As discussed in Note 1 to the consolidated financial statements, the Company has suffered losses and negative cash flow from operations, and has an accumulated deficit as of December 31, 2023, that raises substantial doubt about its ability to continue as a going concern. Management’s plans in regard to these matters are described in Note 1. The consolidated financial statements do not include any adjustments that might result from the outcome of this uncertainty.
Basis for Opinion
These consolidated financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s consolidated financial statements based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (“PCAOB”) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the consolidated financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor were we engaged to perform, an audit of its internal control over financial reporting. As part of our audit,audits we are required to obtain an understanding of internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company’s internal control over financial reporting. Accordingly, we express no such opinion.
Our audits included performing procedures to assess the risks of material misstatement of the consolidated financial statements, whether due to error or fraud, and performing procedures to respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the consolidated financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the consolidated financial statements. We believe that our audits provide a reasonable basis for our opinion.
/s/ Moss AdamsBaker Tilly US, LLP
Seattle, Washington
March 30, 2022
We have served as the Company's auditor since 2018.2019.

Tewksbury, Massachusetts
March 29, 2024

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ANGION BIOMEDICA CORP.ELICIO THERAPEUTICS, INC.
Consolidated Balance SheetsLiquidity and Capital Resources
(Sources and Uses of Liquidity
Our operations through December 31, 2023 have been financed primarily by aggregate net proceeds of $106.6 million from the issuance of common stock, convertible preferred stock, convertible notes, the exercise of stock options and common stock warrants and proceeds from the Merger. Since inception, we have had significant operating losses. Our net loss was $35.2 million and $28.2 million for the years ended December 31, 2023 and 2022, respectively. As of December 31, 2023, we had an accumulated deficit of $142.2 million and $12.9 million in thousands, except sharecash and per share amounts)cash equivalents. Our primary use of cash is to fund operating expenses, which consist primarily of research and development expenditures, and to a lesser extent, general and administrative expenditures. Cash used to fund operating expenses is impacted by the timing of when we pay these expenses, as reflected in the change in our outstanding accounts payable and accrued expenses.
December 31,
20212020
ASSETS
Current assets
Cash and cash equivalents$88,756 $34,607 
Grants receivable806 — 
Prepaid expenses and other current assets1,685 7,690 
Total current assets91,247 42,297 
Property and equipment, net451 156 
Right of use assets3,986 4,072 
Investments in related parties723 822 
Other assets106 — 
Total assets$96,513 $47,347 
LIABILITIES AND STOCKHOLDERS' EQUITY (DEFICIT)
Current liabilities
Accounts payable$4,710 $5,578 
Accrued expenses3,219 6,665 
Lease liability—current894 611 
Financing obligation—current58 — 
Deferred revenue—current2,301 3,942 
Warrant liability114 10,704 
Convertible promissory notes payable at fair value— 51,170 
Series C convertible preferred stock at amortized cost— 26,001 
Series C convertible preferred stock at fair value— 2,518 
Other short-term debt— 260 
Total current liabilities11,296 107,449 
Lease liability—noncurrent3,475 3,847 
Financing obligation—noncurrent235 — 
Deferred revenue—noncurrent— 25,865 
Other long-term debt— 635 
Total liabilities15,006 137,796 
Commitments and contingencies—Note 1100
Stockholders' equity (deficit)
Common stock, $0.01 par value per share; 30,000,000 authorized shares; 29,959,060 and 15,632,809 shares issued as of December 31, 2021 and 2020, respectively; 29,959,060 and 15,316,721 shares outstanding as of December 31, 2021 and 2020, respectively300 156 
Treasury stock, zero and 316,088 shares outstanding as of December 31, 2021 and 2020, respectively— (1,846)
Additional paid-in capital296,445 72,136 
Accumulated other comprehensive loss(103)(333)
Accumulated deficit(215,135)(160,562)
Total stockholders' equity (deficit)81,507 (90,449)
Total liabilities and stockholders' equity (deficit)$96,513 $47,347 
Our losses from operations, negative operating cash flows and accumulated deficit, as well as the additional capital needed to fund operations for at least twelve months following the issuance of the consolidated financial statements, raise substantial doubt about our ability to continue as a going concern. We expect to incur substantial expenditures in the foreseeable future for the development of our product candidates and will require additional financing to continue this development. The consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K have been prepared on a basis that assumes that we will continue as a going concern, which contemplates the realization of assets and satisfaction of liabilities in the normal course of business. The consolidated financial statements do not include any adjustments relating to the recoverability and classification of recorded asset amounts or the amounts and classification of liabilities that might be necessary should we be unable to continue as a going concern. We plan to address this condition through the sale of common stock in public
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offerings and/or private placements, debt financings, or through other capital sources, including licensing arrangements, partnerships and collaborations with other companies or other strategic transactions. However, there is no assurance that we will be successful in raising additional capital or that such additional funds will be available on acceptable terms, if at all. Should we be unable to raise this amount of capital our operating plans will be limited to the amount of capital that we can access. We may also consider steps to reduce our operating expenses. There can be no assurances that we will be successful in any of the foregoing.
Summary Statement of Cash Flows

The following table sets forth a summary of our net cash flow activity for the years ended December 31, 2023 and 2022 (in thousands):
Year Ended December 31,
20232022
Net cash provided by (used in)
Operating activities$(32,694)$(22,179)
Investing activities(32)(654)
Financing activities38,613 21,202 
Effect of foreign currency on cash— — 
Net (decrease) increase in cash$5,887 $(1,631)
Operating activities
For the year ended December 31, 2023, net cash used in operating activities was $32.7 million, which primarily consisted of a net loss of $35.2 million and the change in net operating assets and liabilities of $0.1 million partially offset by the net non-cash charges of $2.6 million. The change in net operating assets and liabilities of $0.1 million was the result of a $0.7 million decrease in the deferred research obligation, $0.8 million decrease in prepaid assets, and $0.8 million decrease in the operating lease liability offset by an increase in accounts payable and accrued expenses of $2.2 million. The $2.6 million of net non-cash charges were related to $1.1 million of interest expense related to the accretion of promissory notes payable, $1.2 million of stock-based compensation, $0.8 million related to the amortization of the right-of-use asset, $0.4 million of depreciation, $0.1 million loss on disposal of property and equipment partially offset by $0.4 million increase in the fair value of the embedded derivative associated with the promissory notes payable and $0.6 million of gain on the extinguishment of the promissory notes payable.
For the year ended December 31, 2022, net cash used in operating activities was $22.2 million, which primarily consisted of a net loss of $28.2 million and a change in net operating assets and liabilities of $0.2 million, partially offset by net non-cash charges of $6.2 million. The change in net operating assets and liabilities of $0.2 million was the result of a $1.8 million decrease in prepaid assets and a $0.5 million decrease in the operating lease liability offset by an increase in accounts payable and accrued expenses of $0.8 million, and an increase of the deferred research obligation of $1.4 million. The net non-cash charges of $6.2 million were primarily related to $3.6 million of non-cash interest expense, $0.9 million of non-cash change in the fair value of the embedded derivative, $0.4 million of depreciation expense, $0.7 million related to amortization of the right-of-use asset associated with our operating leases and $0.6 million of stock-based compensation expense.
Investing activities
For the year ended December 31, 2023, an immaterial amount of cash was provided or used in investing activities, and for the year ended December 31, 2022, net cash used in investing activities was $0.7 million, primarily used to purchase capital equipment.
Financing activities
For the year ended December 31, 2023, net cash provided by financing activities was $38.6 million, comprised of $31.6 million of net proceeds from the Merger and $7.0 million of proceeds from the sale of common stock. For the year ended December 31, 2022, net cash provided by financing activities was $21.2 million, comprised of $21.1 million of net proceeds from the issuance of Series C preferred stock and $0.1 million of proceeds from the exercise of common stock options.
Future Cash Needs and Funding Requirements
Based on our current operating plan, we believe our cash and cash equivalents will be sufficient to fund our planned operations into the third quarter of 2024. However, we have based our projections of operating capital requirements on assumptions that may prove to be incorrect and we may use all our available capital resources
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sooner than we expect. We are unable to estimate the exact amount of our operating capital requirements. The amount and timing of our future funding requirements will depend on many factors, including, but not limited to:
the scope, progress, results and costs of researching and developing product candidates, and conducting preclinical studies and clinical trials;

the outcome of any future clinical trials, for any existing or future product candidates;
The accompanying noteswhether we are an integral partable to take advantage of any FDA expedited development and approval programs for any of our product candidates;
the outcome, costs and timing of seeking and obtaining and maintaining FDA and any foreign regulatory approvals;
the costs associated with any delays we may encounter as a result of evolving regulatory requirements or adverse results with respect to any of our product candidates;
the number and characteristics of product candidates we pursue, including product candidates in preclinical development;
the ability of our product candidates to progress through clinical development successfully;
our need to expand our research and development activities, including to conduct additional clinical trials;
market acceptance of our product candidates, including physician adoption, market access, pricing and reimbursement;
the costs of acquiring, licensing or investing in businesses, products, product candidates and technologies;
our ability to maintain, expand and defend the scope of our intellectual property portfolio, including the amount and timing of any payments potentially required to make, or that we may receive, in connection with the licensing, filing, prosecution, defense and enforcement of any patents or other intellectual property rights;
our need and ability to hire additional personnel, including management, clinical development, medical and commercial personnel;
the effect of competing technological, market developments and government policy;
the costs associated with being a public company, including our need to implement additional internal systems and infrastructure, including financial and reporting systems;
the costs associated with securing and establishing commercialization and manufacturing capabilities, as well as those associated with packaging, warehousing and distribution;
the economic and other terms, timing of and success of our existing licensing arrangements and any collaboration, licensing or other arrangements into which we may enter in the future and timing and amount of payments thereunder; and
the timing, receipt and amount of sales and general commercial success of any future approved products, if any.
Until such time as we can generate significant revenue from sales of product candidates, if ever, we expect to finance our operations through the sale of common stock in public offerings and/or private placements, debt financings, or through other capital sources, including licensing arrangements, partnerships and collaborations with other companies or other strategic transactions. Adequate funding may not be available to us on acceptable terms, or at all. To the extent we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our stockholders will be or could be diluted, and the terms of these consolidated financial statements.securities may include liquidation or other preferences that adversely affect the rights of our common stockholders. Debt financing and equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we raise funds through additional collaborations, or other similar arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to and/or may reduce the value of our common stock. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or commercialization efforts or grant rights to develop and market our product candidates even if we would otherwise prefer to develop and market such product candidates ourselves.
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ANGION BIOMEDICA CORP.Critical Accounting Policies and Significant Judgments and Estimates
Consolidated StatementsOur management’s discussion and analysis of Operationsour financial condition and Comprehensive Loss
(results of operations is based on our consolidated financial statements, which have been prepared in thousands, except share and per share amounts)
Year Ended December 31,
20212020
Revenue:
Contract revenue$27,506 $193 
Grant revenue806 2,687 
Total revenue28,312 2,880 
Operating expenses:
Cost of grant revenue433 1,190 
Research and development48,698 38,977 
General and administrative18,488 17,986 
Total operating expenses67,619 58,153 
Loss from operations(39,307)(55,273)
Other income (expense)
Change in fair value of warrant liability(2,919)(4,910)
Change in fair value of convertible notes(7,469)(11,353)
Change in fair value of Series C convertible preferred stock(3,592)(264)
Foreign exchange transaction gain (loss)(245)668 
Loss on disposal of fixed assets— (58)
Gain upon debt extinguishment905 — 
Losses in equity method investment(99)(71)
Interest income (expense), net(1,847)(8,846)
Total other income (expense)(15,266)(24,834)
Net loss(54,573)(80,107)
Other comprehensive loss:
Foreign currency translation adjustment230 (333)
Comprehensive loss$(54,343)$(80,440)
Net loss per common share, basic and diluted$(1.93)$(5.43)
Weighted average common shares outstanding, basic and diluted28,244,825 14,762,120 


accordance with U.S. generally accepted accounting principles (“GAAP”). The accompanying notes are an integral partpreparation of these consolidated financial statements.statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the consolidated financial statements, as well as the reported expenses incurred during the reporting periods. Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. We believe that the accounting policies discussed below are critical to understanding our historical and future performance, as these policies relate to the more significant areas involving management’s judgments and estimates.
Going Concern
Our evaluation of our ability to continue as a going concern requires us to evaluate our future sources and uses of cash sufficient to fund our currently expected operations in conducting research and development activities one year from the date our audited consolidated financial statements are issued. We evaluate the probability associated with each source and use of cash resources in making our going concern determination. The research and development of pharmaceutical products is inherently subject to uncertainty.
Research and Development Costs
We will incur substantial expenses associated with manufacturing and clinical trials. Accounting for clinical trials relating to activities performed by contract research organizations (“CROs”) and other external vendors requires management to exercise significant estimates in regard to the timing and accounting for these expenses. We estimate costs of research and development activities conducted by service providers, which include the conduct of sponsored research, preclinical studies and contract manufacturing activities. The diverse nature of services being provided under CROs and other arrangements, the different compensation arrangements that exist for each type of service and the lack of timely information related to certain clinical activities complicates the estimation of accruals for services rendered by CROs and other vendors in connection with clinical trials. We record the estimated costs of research and development activities based upon the estimated amount of services provided but not yet invoiced and include these costs in the accrued expenses or prepaid expenses on the balance sheets and within research and development expense on the consolidated statements of operations and comprehensive loss. In estimating the duration of a clinical study, we evaluate the start-up, treatment and wrap-up periods, compensation arrangements and services rendered attributable to each clinical trial and fluctuations are regularly tested against payment plans and trial completion assumptions.
We estimate these costs based on factors such as estimates of the work completed and budget provided and in accordance with agreements established with our collaboration partners and third-party service providers. We make significant judgments and estimates in determining the accrued liabilities and prepaid expense balances in each reporting period. As actual costs become known, we adjust our accrued liabilities or prepaid expenses. We have not experienced any material differences between accrued costs and actual costs incurred since our inception.
Our expenses related to clinical trials will be based on estimates of patient enrollment and related expenses at clinical investigator sites as well as estimates for the services received and efforts expended pursuant to contracts with multiple research institutions and CROs that may be used to conduct and manage clinical trials on our behalf. We will accrue expenses related to clinical trials based on contracted amounts applied to the level of patient enrollment and activity. If timelines or contracts are modified based upon changes in the clinical trial protocol or scope of work to be performed, we will modify our estimates of accrued expenses accordingly on a prospective basis.
Leases
ASU No. 2016-02, Leases (ASC 842) establishes a right-of-use model (“ROU”) that requires a lessee to recognize a ROU asset and corresponding lease liability on the balance sheet for all leases with a term longer than 12 months. Leases will be classified as finance or operating, with classification affecting the pattern and classification of expense recognition in the consolidated statements of operations and comprehensive loss as well as the reduction of the right of use asset.
At the inception of an arrangement, we determine whether the arrangement is or contains a lease based on specific facts and circumstances, the existence of an identified asset(s), if any, and our control over the use of the identified asset(s), if applicable. Operating lease liabilities and their corresponding ROU assets are recorded based on the present value of future lease payments over the expected lease term. The interest rate implicit in lease contracts is typically not readily determinable. As such, we will utilize the incremental borrowing rate, which is the
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rate incurred to borrow on a collateralized basis over a similar term an amount equal to the lease payments in a similar economic environment.
We have elected to combine lease and non-lease components as a single component. Operating leases are recognized on the consolidated balance sheet as ROU lease assets, current lease liabilities and non-current lease liabilities. Fixed rents are included in the calculation of the lease balances, while variable costs paid for certain operating and pass-through costs are excluded. Lease expense is recognized over the expected term on a straight-line basis.
Stock-based Compensation
Prior to the Merger, we issued equity-based compensation awards through the granting of options, which generally vest over four years. We account for equity-based compensation in accordance with Accounting Standards Codification 718, Compensation - Stock Compensation (“ASC 718”). In accordance with ASC 718, compensation cost is measured at estimated fair value at grant date and is included as compensation expense over the vesting period during which service is provided in exchange for the award. Compensation cost of awards that contain a performance condition are recognized when success is considered probable during the performance period.
We use the Black-Scholes option pricing model (“Black-Scholes”) to determine fair value of our options. Black-Scholes includes various assumptions, including the fair value of common shares, expected life of incentive shares, the expected volatility, expected dividend yield, and the expected risk-free interest rate. These assumptions reflect our best estimates, but they involve inherent uncertainties based on market conditions generally outside our control. As a result, if other assumptions had been used, equity-based compensation cost could have been materially impacted. Furthermore, if we use different assumptions for future grants, equity-based compensation cost could be materially impacted in future periods.
The risk-free interest rate is estimated using the weighted average rate of return on U.S. Treasury notes with a life that approximates the expected life of the option. The expected term of options granted to employees was calculated using the simplified method, which represents the average of the contractual term of the option and the weighted-average vesting period of the option. We use the simplified method because we do not have sufficient historical option exercise data to provide a reasonable basis upon which to estimate expected term. The contractual life of the option was used for the expected life of options granted to non-employees. Expected volatility is based on the weighted average of the historical volatility of a peer group of publicly traded companies. The assumed dividend yield is based upon our expectation of not paying dividends in the foreseeable future.
We will continue to use judgment in evaluating the assumptions utilized for our equity-based compensation expense calculations on a prospective basis. In addition to the assumptions used in the Black-Scholes model, the amount of equity-based compensation expense we recognize in our consolidated financial statements includes incentive share forfeitures as they occurred.
Subsequent to the effective date of the Merger, we determine the fair value of our common stock based on the closing price of our common stock as reported by Nasdaq on the date of grant.
Derivative Financial Instruments
The convertible notes include an embedded derivative requiring bifurcation in accordance with Accounting Standards Codification (“ASC”) 815, Derivatives and Hedging. The valuation of this instrument is determined using widely accepted valuation technique including the probability weighted expected return model. The fair value was determined using a model with the assumptions for equity value proceeds, probability of occurrence of various liquidation scenarios, timeline to liquidity and risk-free interest rate. The fair value of this derivative instrument is measured at each reporting period with changes in fair value reported in earnings. On October 18, 2022, in conjunction with the shares of Series C preferred stock issued on this same date, the convertible notes payable totaling $14.5 million and the related accrued interest totaling $1.1 million automatically converted into 1,370,187 shares of Series C preferred stock at an 80% discount to the Series C preferred stock issuance price per share of $14.23, or $11.39 per share. Just prior to settlement, the fair value of the embedded derivative was marked to market a final time to the aggregate value of $3.9 million. We recorded an immaterial gain on extinguishment related to the difference in the total of convertible notes payable, total accrued interest and the final fair value of the embedded derivative versus the value of the Series C preferred stock shares issued based on the original issuance price of $14.23 per share.
Contractual Obligations and Commitments
The following table summarizes our contractual obligations as of December 31, 2023:

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Payments due by period
(in thousands)TotalLess than one yearOne to two yearsThree to four yearsFive and more years
Leases$8,817 $1,427 $1,350 $2,808 $3,232 

We enter into contracts in the normal course of business with third-party service providers for clinical trials, preclinical research studies and testing, manufacturing and other services and products for operating purposes. We have not included our payment obligations under these contracts in the table as these contracts generally provide for termination upon notice, and therefore, we believe that our non-cancelable obligations under these agreements are not material and we cannot reasonably estimate the timing of if and when they will occur. We could also enter into additional research, manufacturing, supplier and other agreements in the future, which may require up-front payments and even long-term commitments of cash.
In January 2016, we licensed certain intellectual property from MIT on terms that have been amended from time to time. The license term extends until terminated by either party under certain provisions. We are required to pay certain contractual maintenance and milestone payments related to clinical trials and royalties on product sales over the term of the contract, with minimum annual royalty payments commencing in the calendar year after commercialization.
Recent Accounting Pronouncements
See Note 2, “Summary of Significant Accounting Policies” in the Notes to the Consolidated Financial Statements set forth in Item 8 of this Annual Report on Form 10-K for a full description of recent accounting standards.
Emerging Growth Company and Smaller Reporting Company Status
We are a smaller reporting company and an emerging growth company, as defined under the JOBS Act. Under the JOBS Act, emerging growth companies can delay the adoption of new or revised accounting standards issued subsequent to the enactment of the JOBS Act until such time as those standards apply to private companies. Other exemptions and reduced reporting requirements under the JOBS Act for emerging growth companies include presentation of only two years of audited financial statements in a registration statement for an initial public offering, an exemption from the requirement to provide an auditor's report on internal controls over financial reporting pursuant to Sarbanes-Oxley Act of 2002, as amended (“Sarbanes-Oxley”) an exemption from any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation, and less extensive disclosure about our executive compensation arrangements. We have elected to use the extended transition period for complying with new or revised accounting standards that have different effective dates for public and private companies until the earlier of the date that (i) we are no longer an emerging growth company or (ii) we affirmatively and irrevocably opt out of the extended transition period provided in the JOBS Act. As a result, our consolidated financial statements may not be comparable to companies that comply with new or revised accounting standards as of public company effective dates.
We will remain an emerging growth company until the earliest of (i) December 31, 2026, (ii) the last day of our first fiscal year in which we have total annual gross revenue of $1.235 billion or more, (iii) the date on which we are deemed to be a "large accelerated filer," as defined in Rule 12b-2 under the Securities Exchange Act of 1934, as amended (the “Exchange Act”), which means the market value of equity securities that is held by non-affiliates exceeds $700 million as of the last business day of our most recently completed second fiscal quarter and (iv) the date on which we have issued more than $1.0 billion in non-convertible debt securities during the prior three-year period.
Even after we no longer qualify as an emerging growth company, we may still qualify as a "smaller reporting company" and/or “non-accelerated filer” which may allow us to take advantage of many of the same exemptions from disclosure requirements including not being required to comply for a period of time with the auditor attestation requirements of Section 404 of Sarbanes-Oxley, and reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements.
Item 7A. Quantitative and Qualitative Disclosures About Market Risk
We are a smaller reporting company as defined by Rule 12b-2 of the Exchange Act and are not required to provide the information required under this item.
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ANGION BIOMEDICA CORP.
ConsolidatedItem 8. Financial Statements of Stockholders' Equity (Deficit)
(in thousands, except share amounts)


Common StockTreasury Stock
Additional
Paid-in
Capital
Accumulated Other Comprehensive loss
Accumulated
Deficit
Total
Stockholders'
Equity
(Deficit)
SharesAmountSharesAmount
Balance as of December 31, 201914,758,718$148 (312,164)$(1,810)$63,531 $— $(80,455)$(18,586)
Issuance of broker warrants3,0953,095
Exercise of broker warrants572,9466(2)4
Exercise of warrants93,3491750751
Exercise of stock options194,42714647
Restricted stock units releases13,369
Return of common stock to pay withholding taxes on restricted stock(3,924)(36)(36)
Stock-based compensation4,7164,716
Foreign currency translation adjustment(333)(333)
Net loss(80,107)(80,107)
Balance as of December 31, 202015,632,809$156 (316,088)$(1,846)$72,136 $(333)$(160,562)$(90,449)















and Supplementary Data.

The accompanying notesfinancial statements of Elicio Therapeutics, Inc., listed below are an integral partset forth in Item 8 of these consolidated financial statements.this Annual Report for the years ended December 31, 2023 and 2022:
ELICIO THERAPEUTICS, INC.
INDEX TO CONSOLIDATED FINANCIAL STATEMENTS
Page
Report of Independent Registered Public Accounting Firm (Baker Tilly US, LLP, Tewksbury, Massachusetts, PCAOB ID: 23)
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ANGION BIOMEDICA CORP.
Consolidated Statements of Stockholders' Equity (Deficit)
(in thousands, except share amounts)

Common StockTreasury Stock
Additional
Paid-in
Capital
Accumulated Other Comprehensive loss
Accumulated
Deficit
Total
Stockholders'
Equity
(Deficit)
SharesAmountSharesAmount
Balance as of December 31, 202015,632,809$156 (316,088)$(1,846)$72,136 $(333)$(160,562)$(90,449)
Issuance of common stock upon initial public offering, net of issuance costs, discount, and commissions of $9.3 million5,750,0005882,65782,715
Issuance of common stock upon Concurrent Private Placement, net of issuance costs of $0.7 million1,562,5001624,23424,250
Conversion of convertible preferred stock into common stock upon IPO2,234,6402235,73235,754
Conversion of convertible notes into common stock upon initial public offering3,636,1893658,14358,179
Conversion of convertible notes prior to IPO33,978460460
Net exercise of warrants upon initial public offering844,335913,50013,509
Fractional shares paid out related to the forward stock split(10)(10)
Exercise of broker warrants47,188
Exercise of warrants130,5292859861
Exercise of stock options152,9391979980
Restricted stock units releases414,89641418
Return of common stock to pay withholding taxes on restricted stock(164,855)(2,364)(94)(2,458)
Retirement of treasury stock(480,943)(4)480,9434,210(4,206)
Stock-based compensation12,04112,041
Foreign currency translation adjustment230230
Net loss(54,573)(54,573)
Balance as of December 31, 202129,959,060$300 $— $296,445 $(103)$(215,135)$81,507 

The accompanying notes are an integral part of these consolidated financial statements.
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ANGION BIOMEDICA CORP.REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
ConsolidatedTo the Stockholders and the Board of Directors of Elicio Therapeutics, Inc.
Opinion on the Financial Statements
We have audited the accompanying consolidated balance sheets of Cash FlowsElicio Therapeutics, Inc. (the “Company”) as of December 31, 2023 and 2022, the related consolidated statements of operations and comprehensive loss, convertible preferred stock and stockholders’ equity (deficit), and cash flows, for each of the two years in the period ended December 31, 2023, and the related notes (collectively referred to as the “consolidated financial statements”). In our opinion, the consolidated financial statements present fairly, in all material respects, the financial position of the Company as of December 31, 2023 and 2022, and the results of its operations and its cash flows for each of the two years in the period ended December 31, 2023, in conformity with accounting principles generally accepted in the United States of America.
(Going Concern Uncertainty
The accompanying consolidated financial statements have been prepared assuming that the Company will continue as a going concern. As discussed in thousands)Note 1 to the consolidated financial statements, the Company has suffered losses and negative cash flow from operations, and has an accumulated deficit as of December 31, 2023, that raises substantial doubt about its ability to continue as a going concern. Management’s plans in regard to these matters are described in Note 1. The consolidated financial statements do not include any adjustments that might result from the outcome of this uncertainty.
Basis for Opinion
These consolidated financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s consolidated financial statements based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (“PCAOB”) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the consolidated financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits we are required to obtain an understanding of internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company’s internal control over financial reporting. Accordingly, we express no such opinion.
Our audits included performing procedures to assess the risks of material misstatement of the consolidated financial statements, whether due to error or fraud, and performing procedures to respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the consolidated financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the consolidated financial statements. We believe that our audits provide a reasonable basis for our opinion.
/s/ Baker Tilly US, LLP
We have served as the Company's auditor since 2019.

Year Ended December 31,
20212020
Cash flows from operating activities
Net loss$(54,573)$(80,107)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation91 98 
Amortization of right of use assets710 530 
Amortization of debt issuance costs1,884 7,661 
Non-cash placement agent fee— 1,683 
PPP Loan forgiveness(905)— 
Stock-based compensation12,041 4,716 
Change in fair value of convertible notes7,469 11,353 
Change in fair value of Series C convertible preferred stock3,592 264 
Change in fair value of warrant liability2,919 4,910 
Impairment of leased assets— 58 
Losses from equity investment96 71 
Distribution from equity investment106 
Changes in operating assets and liabilities:
Grants receivable(806)440 
Prepaid expenses and other current assets4,016 (2,020)
Other assets(106)— 
Accounts payable(866)(5,607)
Accrued expenses11 3,709 
Lease liabilities(713)(560)
Deferred revenue(27,506)29,807 
Net cash used in operating activities(52,643)(22,888)
Cash flows from investing activities
Purchase of fixed assets(382)(41)
Net cash used in investing activities(382)(41)
Cash flows from financing activities
Net proceeds from issuance of common stock upon IPO and Concurrent Private Placement, net of discount, commissions and offering costs107,487 (522)
Proceeds from issuance of convertible notes and warrants— 31,223 
Proceeds from issuance of Series C convertible preferred stock, net of issuance costs— 20,047 
Proceeds from loan from PPP— 895 
Proceeds from financing obligation302 — 
Proceeds from RSU settlement18 — 
Payment of financing obligation(9)0
Fractional share payments related to the forward stock split(10)— 
Taxes paid related to net share settlement upon vesting of restricted stock awards(2,458)(36)
Exercise of broker warrants— 
Exercise of warrants861 751 
Exercise of stock options980 47 
Net cash provided by financing activities107,171 52,409 
Effect of foreign currency on cash(444)
Net increase in cash and cash equivalents54,149 29,036 
Cash and cash equivalents at the beginning of the period34,607 5,571 
Cash and cash equivalents at the end of the period$88,756 $34,607 
Supplemental disclosure of cash flow information:
Cash paid for interest$7 $ 
Supplemental disclosure of noncash investing and financing activities:
Retirement of treasury stock$4,210 $— 
Conversion of convertible notes into common stock prior to IPO$460 $— 
Tewksbury, Massachusetts
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Conversion of convertible notes to common stock$58,639 $— 
Conversion of Series C preferred stock to common stock upon IPO$35,754 $— 
Net exercise of warrants upon IPO$13,509 $— 
Issuance of broker warrants with Series C convertible preferred stock$— $1,412 
Conversion of convertible notes to Series C convertible preferred stock$— $2,254 
Accrued interest premium for Series C convertible preferred stock$— $295 
Right of use assets exchanged for operating lease liabilities$624 $88 
Convertible notes issued in receivable$— $5,000 
Deferred offering costs in accrued expenses or accounts payable$— $1,443 
Fixed assets purchased in accrued expenses or accounts payable$$
March 29, 2024

The accompanying notes are an integral part of these consolidated financial statements.
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ANGION BIOMEDICA CORP.
Notes to Consolidated Financial StatementsELICIO THERAPEUTICS, INC.


Note 1—Description of the Business and Financial Condition

Angion Biomedica Corp. ("Angion" or", the "Company") is a clinical biopharmaceutical company focused on the discovery, development and commercialization of novel small molecule therapeutics to address acute organ injuries and fibrotic diseases. The Company was incorporated in Delaware in 1998.
Forward Stock Split
On January 25, 2021, the board of directors of the Company approved an amendment to the Company's certificate of incorporation to effect a forward stock split ("Forward Split") of shares of the Company's common stock on a one-for 1.55583 basis, which was effected on February 1, 2021. All references to common stock, convertible preferred stock, warrants to purchase common stock, stock options, restricted stock awards ("RSAs"), restricted stock units ("RSUs"), including restricted stock units with non-market performance and service conditions ("PSUs"), per share amounts and related information contained in the consolidated financial statements have been retroactively adjusted to reflect the effect of the forward stock split for all periods presented. No fractional shares of the Company's common stock were issued in connection with the Forward Split. Any fractional share resulting from the Forward Split was rounded down to the nearest whole share, and any stockholder entitled to fractional shares as a result of the Forward Split will received a cash payment in lieu of receiving fractional shares.
Initial Public Offering and the Concurrent Private Placement
On February 9, 2021, the Company’s registration statement on Form S-1 (File No. 333-252177) relating to its initial public offering (IPO) of common stock became effective. The IPO closed on February 9, 2021 at which time the Company issued 5,750,000 shares of its common stock at a price to the public of $16.00 per share, which includes the full exercise by the underwriters of their option to purchase an additional 750,000 shares of common stock. In addition to the shares being sold in the IPO, the Company sold an additional 1,562,500 shares of its common stock at the public offering price of $16.00 per share to entities affiliated with Vifor International, Ltd., an existing stockholder (the “Concurrent Private Placement”) for gross proceeds of $25.0 million. Subsequent to the closing of the IPO, all of the outstanding shares of convertible preferred stock and outstanding convertible notes automatically converted into shares of common stock.
The IPO and Concurrent Private Placement generated aggregate net proceeds of approximately $107.0 million, after deducting the underwriting discounts and commissions, private placement fee and estimated offering expenses payable by the Company.
Subsequent to the closing of the IPO, there were no shares of convertible preferred stock outstanding and there were no convertible notes outstanding. In connection with the closing of the IPO, the Company restated its Restated Certificate of Incorporation to change the authorized capital stock to 300,000,000 shares designated as common stock, and 10,000,000 shares designated as preferred stock, with a par value of $0.01 per share and $0.01 per share, respectively.
Liquidity and Capital Resources
Sources and Uses of Liquidity
Our operations through December 31, 2023 have been financed primarily by aggregate net proceeds of $106.6 million from the issuance of common stock, convertible preferred stock, convertible notes, the exercise of stock options and common stock warrants and proceeds from the Merger. Since inception, the Company has devoted substantially all of its effortswe have had significant operating losses. Our net loss was $35.2 million and financial resources to conducting research and development activities, including drug discovery and pre-clinical studies and clinical trials, establishing and maintaining its intellectual property portfolio, organizing and staffing the Company, business planning, raising capital and providing general and administrative support for these operations. The Company has incurred losses from operations and negative cash flows from operating activities since inception and expects to continue to incur substantial losses$28.2 million for the next several years as it continues to fully developended December 31, 2023 and if approved, commercialize its product candidates.2022, respectively. As of December 31, 2021, the Company2023, we had $88.8an accumulated deficit of $142.2 million and $12.9 million in cash and cash equivalentsequivalents. Our primary use of cash is to fund operating expenses, which consist primarily of research and andevelopment expenditures, and to a lesser extent, general and administrative expenditures. Cash used to fund operating expenses is impacted by the timing of when we pay these expenses, as reflected in the change in our outstanding accounts payable and accrued expenses.
Our losses from operations, negative operating cash flows and accumulated deficit, of $215.1 million. Prioras well as the additional capital needed to its IPO, the Company has funded itsfund operations through United States government grants,for at least twelve months following the issuance of convertible notes (see Note 6), salesthe consolidated financial statements, raise substantial doubt about our ability to continue as a going concern. We expect to incur substantial expenditures in the foreseeable future for the development of convertible preferred stockour product candidates and will require additional financing to continue this development. The consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K have been prepared on a basis that assumes that we will continue as a going concern, which contemplates the realization of assets and satisfaction of liabilities in the normal course of business. The consolidated financial statements do not include any adjustments relating to the recoverability and classification of recorded asset amounts or the amounts and classification of liabilities that might be necessary should we be unable to continue as a going concern. We plan to address this condition through the sale of common stock (see Notes 7) and warrants (see Note 10) and licensing agreements (see Note 12).
The planned expansion of the Company's clinical and discovery programs will require significant funds. Management expects to continue to incur significant expenses and to incur operating losses for the foreseeablein public
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ANGION BIOMEDICA CORP.
offerings and/or private placements, debt financings, or through other capital sources, including licensing arrangements, partnerships and collaborations with other companies or other strategic transactions. However, there is no assurance that we will be successful in raising additional capital or that such additional funds will be available on acceptable terms, if at all. Should we be unable to raise this amount of capital our operating plans will be limited to the amount of capital that we can access. We may also consider steps to reduce our operating expenses. There can be no assurances that we will be successful in any of the foregoing.
Summary Statement of Cash Flows
The following table sets forth a summary of our net cash flow activity for the years ended December 31, 2023 and 2022 (in thousands):
Year Ended December 31,
20232022
Net cash provided by (used in)
Operating activities$(32,694)$(22,179)
Investing activities(32)(654)
Financing activities38,613 21,202 
Effect of foreign currency on cash— — 
Net (decrease) increase in cash$5,887 $(1,631)
Operating activities
For the year ended December 31, 2023, net cash used in operating activities was $32.7 million, which primarily consisted of a net loss of $35.2 million and the change in net operating assets and liabilities of $0.1 million partially offset by the net non-cash charges of $2.6 million. The change in net operating assets and liabilities of $0.1 million was the result of a $0.7 million decrease in the deferred research obligation, $0.8 million decrease in prepaid assets, and $0.8 million decrease in the operating lease liability offset by an increase in accounts payable and accrued expenses of $2.2 million. The $2.6 million of net non-cash charges were related to $1.1 million of interest expense related to the accretion of promissory notes payable, $1.2 million of stock-based compensation, $0.8 million related to the amortization of the right-of-use asset, $0.4 million of depreciation, $0.1 million loss on disposal of property and equipment partially offset by $0.4 million increase in the fair value of the embedded derivative associated with the promissory notes payable and $0.6 million of gain on the extinguishment of the promissory notes payable.
For the year ended December 31, 2022, net cash used in operating activities was $22.2 million, which primarily consisted of a net loss of $28.2 million and a change in net operating assets and liabilities of $0.2 million, partially offset by net non-cash charges of $6.2 million. The change in net operating assets and liabilities of $0.2 million was the result of a $1.8 million decrease in prepaid assets and a $0.5 million decrease in the operating lease liability offset by an increase in accounts payable and accrued expenses of $0.8 million, and an increase of the deferred research obligation of $1.4 million. The net non-cash charges of $6.2 million were primarily related to $3.6 million of non-cash interest expense, $0.9 million of non-cash change in the fair value of the embedded derivative, $0.4 million of depreciation expense, $0.7 million related to amortization of the right-of-use asset associated with our operating leases and $0.6 million of stock-based compensation expense.
Investing activities
For the year ended December 31, 2023, an immaterial amount of cash was provided or used in investing activities, and for the year ended December 31, 2022, net cash used in investing activities was $0.7 million, primarily used to purchase capital equipment.
Financing activities
For the year ended December 31, 2023, net cash provided by financing activities was $38.6 million, comprised of $31.6 million of net proceeds from the Merger and $7.0 million of proceeds from the sale of common stock. For the year ended December 31, 2022, net cash provided by financing activities was $21.2 million, comprised of $21.1 million of net proceeds from the issuance of Series C preferred stock and $0.1 million of proceeds from the exercise of common stock options.
Future Cash Needs and Funding Requirements
Based on our current operating plan, we believe our cash and cash equivalents will be sufficient to fund our planned operations into the third quarter of 2024. However, we have based our projections of operating capital requirements on assumptions that may prove to be incorrect and we may use all our available capital resources
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sooner than we expect. We are unable to estimate the exact amount of our operating capital requirements. The amount and timing of our future funding requirements will depend on many factors, including, but not limited to:
the scope, progress, results and costs of researching and developing product candidates, and conducting preclinical studies and clinical trials;
the outcome of any future clinical trials, for any existing or future product candidates;
whether we are able to take advantage of any FDA expedited development and approval programs for any of our product candidates;
the outcome, costs and timing of seeking and obtaining and maintaining FDA and any foreign regulatory approvals;
the costs associated with any delays we may encounter as a result of evolving regulatory requirements or adverse results with respect to any of our product candidates;
the number and characteristics of product candidates we pursue, including product candidates in preclinical development;
the ability of our product candidates to progress through clinical development successfully;
our need to expand our research and development activities, including to conduct additional clinical trials;
market acceptance of our product candidates, including physician adoption, market access, pricing and reimbursement;
the costs of acquiring, licensing or investing in businesses, products, product candidates and technologies;
our ability to maintain, expand and defend the scope of our intellectual property portfolio, including the amount and timing of any payments potentially required to make, or that we may receive, in connection with the licensing, filing, prosecution, defense and enforcement of any patents or other intellectual property rights;
our need and ability to hire additional personnel, including management, clinical development, medical and commercial personnel;
the effect of competing technological, market developments and government policy;
the costs associated with being a public company, including our need to implement additional internal systems and infrastructure, including financial and reporting systems;
the costs associated with securing and establishing commercialization and manufacturing capabilities, as well as those associated with packaging, warehousing and distribution;
the economic and other terms, timing of and success of our existing licensing arrangements and any collaboration, licensing or other arrangements into which we may enter in the future and timing and amount of payments thereunder; and
the timing, receipt and amount of sales and general commercial success of any future approved products, if any.
Until such time as we can generate significant revenue from sales of product candidates, if ever, we expect to finance our operations through the sale of common stock in public offerings and/or private placements, debt financings, or through other capital sources, including licensing arrangements, partnerships and collaborations with other companies or other strategic transactions. Adequate funding may not be available to us on acceptable terms, or at all. To the extent we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our stockholders will be or could be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our common stockholders. Debt financing and equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we raise funds through additional collaborations, or other similar arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to and/or may reduce the value of our common stock. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or commercialization efforts or grant rights to develop and market our product candidates even if we would otherwise prefer to develop and market such product candidates ourselves.
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Critical Accounting Policies and Significant Judgments and Estimates
Our management’s discussion and analysis of our financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with U.S. generally accepted accounting principles (“GAAP”). The preparation of these consolidated financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the consolidated financial statements, as well as the reported expenses incurred during the reporting periods. Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. We believe that the accounting policies discussed below are critical to understanding our historical and future performance, as these policies relate to the more significant areas involving management’s judgments and estimates.
Going Concern
Our evaluation of our ability to continue as a going concern requires us to evaluate our future sources and uses of cash sufficient to fund our currently expected operations in conducting research and development activities one year from the date our audited consolidated financial statements are issued. We evaluate the probability associated with each source and use of cash resources in making our going concern determination. The research and development of pharmaceutical products is inherently subject to uncertainty.
Research and Development Costs
We will incur substantial expenses associated with manufacturing and clinical trials. Accounting for clinical trials relating to activities performed by contract research organizations (“CROs”) and other external vendors requires management to exercise significant estimates in regard to the timing and accounting for these expenses. We estimate costs of research and development activities conducted by service providers, which include the conduct of sponsored research, preclinical studies and contract manufacturing activities. The diverse nature of services being provided under CROs and other arrangements, the different compensation arrangements that exist for each type of service and the lack of timely information related to certain clinical activities complicates the estimation of accruals for services rendered by CROs and other vendors in connection with clinical trials. We record the estimated costs of research and development activities based upon the estimated amount of services provided but not yet invoiced and include these costs in the accrued expenses or prepaid expenses on the balance sheets and within research and development expense on the consolidated statements of operations and comprehensive loss. In estimating the duration of a clinical study, we evaluate the start-up, treatment and wrap-up periods, compensation arrangements and services rendered attributable to each clinical trial and fluctuations are regularly tested against payment plans and trial completion assumptions.
We estimate these costs based on factors such as estimates of the work completed and budget provided and in accordance with agreements established with our collaboration partners and third-party service providers. We make significant judgments and estimates in determining the accrued liabilities and prepaid expense balances in each reporting period. As actual costs become known, we adjust our accrued liabilities or prepaid expenses. We have not experienced any material differences between accrued costs and actual costs incurred since our inception.
Our expenses related to clinical trials will be based on estimates of patient enrollment and related expenses at clinical investigator sites as well as estimates for the services received and efforts expended pursuant to contracts with multiple research institutions and CROs that may be used to conduct and manage clinical trials on our behalf. We will accrue expenses related to clinical trials based on contracted amounts applied to the level of patient enrollment and activity. If timelines or contracts are modified based upon changes in the clinical trial protocol or scope of work to be performed, we will modify our estimates of accrued expenses accordingly on a prospective basis.
Leases
ASU No. 2016-02, Leases (ASC 842) establishes a right-of-use model (“ROU”) that requires a lessee to recognize a ROU asset and corresponding lease liability on the balance sheet for all leases with a term longer than 12 months. Leases will be classified as finance or operating, with classification affecting the pattern and classification of expense recognition in the consolidated statements of operations and comprehensive loss as well as the reduction of the right of use asset.
At the inception of an arrangement, we determine whether the arrangement is or contains a lease based on specific facts and circumstances, the existence of an identified asset(s), if any, and our control over the use of the identified asset(s), if applicable. Operating lease liabilities and their corresponding ROU assets are recorded based on the present value of future lease payments over the expected lease term. The interest rate implicit in lease contracts is typically not readily determinable. As such, we will utilize the incremental borrowing rate, which is the
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rate incurred to borrow on a collateralized basis over a similar term an amount equal to the lease payments in a similar economic environment.
We have elected to combine lease and non-lease components as a single component. Operating leases are recognized on the consolidated balance sheet as ROU lease assets, current lease liabilities and non-current lease liabilities. Fixed rents are included in the calculation of the lease balances, while variable costs paid for certain operating and pass-through costs are excluded. Lease expense is recognized over the expected term on a straight-line basis.
Stock-based Compensation
Prior to the Merger, we issued equity-based compensation awards through the granting of options, which generally vest over four years. We account for equity-based compensation in accordance with Accounting Standards Codification 718, Compensation - Stock Compensation (“ASC 718”). In accordance with ASC 718, compensation cost is measured at estimated fair value at grant date and is included as compensation expense over the vesting period during which service is provided in exchange for the award. Compensation cost of awards that contain a performance condition are recognized when success is considered probable during the performance period.
We use the Black-Scholes option pricing model (“Black-Scholes”) to determine fair value of our options. Black-Scholes includes various assumptions, including the fair value of common shares, expected life of incentive shares, the expected volatility, expected dividend yield, and the expected risk-free interest rate. These assumptions reflect our best estimates, but they involve inherent uncertainties based on market conditions generally outside our control. As a result, if other assumptions had been used, equity-based compensation cost could have been materially impacted. Furthermore, if we use different assumptions for future grants, equity-based compensation cost could be materially impacted in future periods.
The risk-free interest rate is estimated using the weighted average rate of return on U.S. Treasury notes with a life that approximates the expected life of the option. The expected term of options granted to employees was calculated using the simplified method, which represents the average of the contractual term of the option and the weighted-average vesting period of the option. We use the simplified method because we do not have sufficient historical option exercise data to provide a reasonable basis upon which to estimate expected term. The contractual life of the option was used for the expected life of options granted to non-employees. Expected volatility is based on the weighted average of the historical volatility of a peer group of publicly traded companies. The assumed dividend yield is based upon our expectation of not paying dividends in the foreseeable future.
We will continue to use judgment in evaluating the assumptions utilized for our equity-based compensation expense calculations on a prospective basis. In addition to the assumptions used in the Black-Scholes model, the amount of equity-based compensation expense we recognize in our consolidated financial statements includes incentive share forfeitures as they occurred.
Subsequent to the effective date of the Merger, we determine the fair value of our common stock based on the closing price of our common stock as reported by Nasdaq on the date of grant.
Derivative Financial Instruments
The convertible notes include an embedded derivative requiring bifurcation in accordance with Accounting Standards Codification (“ASC”) 815, Derivatives and Hedging. The valuation of this instrument is determined using widely accepted valuation technique including the probability weighted expected return model. The fair value was determined using a model with the assumptions for equity value proceeds, probability of occurrence of various liquidation scenarios, timeline to liquidity and risk-free interest rate. The fair value of this derivative instrument is measured at each reporting period with changes in fair value reported in earnings. On October 18, 2022, in conjunction with the shares of Series C preferred stock issued on this same date, the convertible notes payable totaling $14.5 million and the related accrued interest totaling $1.1 million automatically converted into 1,370,187 shares of Series C preferred stock at an 80% discount to the Series C preferred stock issuance price per share of $14.23, or $11.39 per share. Just prior to settlement, the fair value of the embedded derivative was marked to market a final time to the aggregate value of $3.9 million. We recorded an immaterial gain on extinguishment related to the difference in the total of convertible notes payable, total accrued interest and the final fair value of the embedded derivative versus the value of the Series C preferred stock shares issued based on the original issuance price of $14.23 per share.
Contractual Obligations and Commitments
The following table summarizes our contractual obligations as of December 31, 2023:

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Payments due by period
(in thousands)TotalLess than one yearOne to two yearsThree to four yearsFive and more years
Leases$8,817 $1,427 $1,350 $2,808 $3,232 

We enter into contracts in the normal course of business with third-party service providers for clinical trials, preclinical research studies and testing, manufacturing and other services and products for operating purposes. We have not included our payment obligations under these contracts in the table as these contracts generally provide for termination upon notice, and therefore, we believe that our non-cancelable obligations under these agreements are not material and we cannot reasonably estimate the timing of if and when they will occur. We could also enter into additional research, manufacturing, supplier and other agreements in the future, which may require up-front payments and even long-term commitments of cash.
In January 2016, we licensed certain intellectual property from MIT on terms that have been amended from time to time. The license term extends until terminated by either party under certain provisions. We are required to pay certain contractual maintenance and milestone payments related to clinical trials and royalties on product sales over the term of the contract, with minimum annual royalty payments commencing in the calendar year after commercialization.
Recent Accounting Pronouncements
See Note 2, “Summary of Significant Accounting Policies” in the Notes to the Consolidated Financial Statements (Continued)set forth in Item 8 of this Annual Report on Form 10-K for a full description of recent accounting standards.
Emerging Growth Company and Smaller Reporting Company Status
We are a smaller reporting company and an emerging growth company, as defined under the JOBS Act. Under the JOBS Act, emerging growth companies can delay the adoption of new or revised accounting standards issued subsequent to the enactment of the JOBS Act until such time as those standards apply to private companies. Other exemptions and reduced reporting requirements under the JOBS Act for emerging growth companies include presentation of only two years of audited financial statements in a registration statement for an initial public offering, an exemption from the requirement to provide an auditor's report on internal controls over financial reporting pursuant to Sarbanes-Oxley Act of 2002, as amended (“Sarbanes-Oxley”) an exemption from any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation, and less extensive disclosure about our executive compensation arrangements. We have elected to use the extended transition period for complying with new or revised accounting standards that have different effective dates for public and private companies until the earlier of the date that (i) we are no longer an emerging growth company or (ii) we affirmatively and irrevocably opt out of the extended transition period provided in the JOBS Act. As a result, our consolidated financial statements may not be comparable to companies that comply with new or revised accounting standards as of public company effective dates.
We will remain an emerging growth company until the earliest of (i) December 31, 2026, (ii) the last day of our first fiscal year in which we have total annual gross revenue of $1.235 billion or more, (iii) the date on which we are deemed to be a "large accelerated filer," as defined in Rule 12b-2 under the Securities Exchange Act of 1934, as amended (the “Exchange Act”), which means the market value of equity securities that is held by non-affiliates exceeds $700 million as of the last business day of our most recently completed second fiscal quarter and (iv) the date on which we have issued more than $1.0 billion in non-convertible debt securities during the prior three-year period.
Even after we no longer qualify as an emerging growth company, we may still qualify as a "smaller reporting company" and/or “non-accelerated filer” which may allow us to take advantage of many of the same exemptions from disclosure requirements including not being required to comply for a period of time with the auditor attestation requirements of Section 404 of Sarbanes-Oxley, and reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements.
Item 7A. Quantitative and Qualitative Disclosures About Market Risk
We are a smaller reporting company as defined by Rule 12b-2 of the Exchange Act and are not required to provide the information required under this item.
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Item 8. Financial Statements and Supplementary Data.

The financial statements of Elicio Therapeutics, Inc., listed below are set forth in Item 8 of this Annual Report for the years ended December 31, 2023 and 2022:
future. ELICIO THERAPEUTICS, INC.
INDEX TO CONSOLIDATED FINANCIAL STATEMENTS
Page
Report of Independent Registered Public Accounting Firm (Baker Tilly US, LLP, Tewksbury, Massachusetts, PCAOB ID: 23)
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REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
To the Stockholders and the Board of Directors of Elicio Therapeutics, Inc.
Opinion on the Financial Statements
We have audited the accompanying consolidated balance sheets of Elicio Therapeutics, Inc. (the “Company”) as of December 31, 2023 and 2022, the related consolidated statements of operations and comprehensive loss, convertible preferred stock and stockholders’ equity (deficit), and cash flows, for each of the two years in the period ended December 31, 2023, and the related notes (collectively referred to as the “consolidated financial statements”). In our opinion, the consolidated financial statements present fairly, in all material respects, the financial position of the Company as of December 31, 2023 and 2022, and the results of its operations and its cash flows for each of the two years in the period ended December 31, 2023, in conformity with accounting principles generally accepted in the United States of America.
Going Concern Uncertainty
The accompanying consolidated financial statements have been prepared assuming that the Company will continue as a going concern. As discussed in Note 1 to the consolidated financial statements, the Company has evaluatedsuffered losses and concluded there are no conditions or events, considered in the aggregate,negative cash flow from operations, and has an accumulated deficit as of December 31, 2023, that raiseraises substantial doubt about its ability to continue as a going concernconcern. Management’s plans in regard to these matters are described in Note 1. The consolidated financial statements do not include any adjustments that might result from the outcome of this uncertainty.
Basis for a period of one year following the date theseOpinion
These consolidated financial statements are issuedthe responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s consolidated financial statements based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (“PCAOB”) and believesare required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the consolidated financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor were we engaged to perform, an audit of its existinginternal control over financial reporting. As part of our audits we are required to obtain an understanding of internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company’s internal control over financial reporting. Accordingly, we express no such opinion.
Our audits included performing procedures to assess the risks of material misstatement of the consolidated financial statements, whether due to error or fraud, and performing procedures to respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the consolidated financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the consolidated financial statements. We believe that our audits provide a reasonable basis for our opinion.
/s/ Baker Tilly US, LLP
We have served as the Company's auditor since 2019.

Tewksbury, Massachusetts
March 29, 2024

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ELICIO THERAPEUTICS, INC.
Consolidated Balance Sheets
(in thousands, except share and per share amounts)
December 31,
20232022
Assets
Current assets
Cash and cash equivalents$12,894 $6,156 
Restricted cash, current722 1,641 
Prepaid expenses and other current assets2,732 2,920 
Total current assets16,348 10,717 
Property and equipment, net717 1,147 
Operating lease, right-of-use assets6,563 7,350 
Restricted cash, noncurrent685 617 
Other long-term prepaid assets2,833 2,833 
Total assets$27,146 $22,664 
Liabilities, convertible preferred stock, and stockholders’ equity (deficit)
Current liabilities
Accounts payable$4,369 $2,805 
Accrued expenses3,757 1,935 
Deferred research obligation694 1,436 
Operating lease liability, current910 692 
Unvested option exercise liability, current25 — 
Warrant liability11 — 
Total current liabilities9,766 6,868 
Operating lease liability, noncurrent6,007 6,789 
Unvested option exercise liability, noncurrent— 92 
Total liabilities15,773 13,749 
Commitments and contingencies—Note 10
Convertible preferred stock:
Series A convertible preferred stock, $0.06 par value:
no shares and 132,387 shares authorized, issued and outstanding at December 31, 2023 and 2022, respectively
— 7,495 
Series B convertible preferred stock, $0.06 par value:
no shares and 1,927,375 shares authorized, issued and outstanding at December 31, 2023 and 2022, respectively
— 62,944 
Series C convertible preferred stock, $0.06 par value:
no shares and 4,888,798 shares authorized at December 31, 2023 and 2022, respectively; no shares and 2,938,158 shares issued and outstanding at December 31, 2023 and 2022, respectively
— 40,621 
Total convertible preferred stock— 111,060 
Stockholders' equity (deficit):
Common stock, $0.01 par value; 300,000,000 shares authorized at December 31, 2023 and 2022, respectively; 9,618,178 and 320,281 shares issued at December 31, 2023 and 2022, respectively; 9,603,723 and 320,281 shares outstanding as of December 31, 2023 and 2022, respectively96 
Treasury stock, at cost, 14,455 and no shares outstanding as of December 31, 2023 and 2022, respectively(150)— 
Additional paid-in capital153,827 4,860 
Accumulated other comprehensive loss(197)— 
Accumulated deficit(142,203)(107,008)
Total stockholders' equity (deficit)11,373 (102,145)
Total liabilities, convertible preferred stock, and stockholders’ equity (deficit)$27,146 $22,664 

The accompanying notes are an integral part of these consolidated financial statements.
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ELICIO THERAPEUTICS, INC.
Consolidated Statements of Operations and Comprehensive Loss
(in thousands, except share and per share amounts)
Year Ended December 31,
20232022
Operating expenses:
Research and development$23,849 $18,103 
General and administrative11,896 5,630 
Total operating expenses35,745 23,733 
Loss from operations(35,745)(23,733)
Other income (expense)
Change in fair value of warrant liability(2)— 
Change in fair value of embedded derivatives429 (945)
Gain on extinguishment of promissory notes payable605 
Foreign exchange transaction gain204 — 
Interest income373 65 
Interest expense(1,059)(3,597)
Total other income (expense)550 (4,475)
Net loss(35,195)(28,208)
Other comprehensive loss:
Foreign currency translation adjustment(197)— 
Comprehensive loss$(35,392)$(28,208)
Net loss per common share, basic and diluted$(6.96)$(89.27)
Weighted average common shares outstanding, basic and diluted5,056,225 315,998 


The accompanying notes are an integral part of these consolidated financial statements.
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ELICIO THERAPEUTICS, INC.
Consolidated Statements of Convertible Preferred Stock and Stockholders' Equity (Deficit)
(in thousands, except share amounts)


Total Convertible Preferred StockCommon StockTreasury Stock
Additional
Paid-in
Capital
Accumulated Other Comprehensive Loss
Accumulated
Deficit
Total
Stockholders'
Equity (Deficit)
SharesAmountSharesPar ValueSharesAmount
Balance as of December 31, 20224,997,920 $111,060 320,281 $3  $ $4,860 $ $(107,008)$(102,145)
Exercise of stock options—  16,349 — — 126 — — 127 
Vesting of restricted common stock—  5,310 — — — 67 — — 67 
Conversion of preferred stock(4,997,920)(111,060)4,997,920 50 — — 111,010 — — 111,060 
Issuance of common stock to Angion stockholders as a result of Merger and reset to par of $0.01, net of transaction costs of $2.4 million—  3,012,854 30 — — 19,496 — — 19,526 
Settlement of promissory notes in connection with Merger—  — — — — 10,027 — — 10,027 
Issuance of common stock upon accelerated vesting of restricted stock units due to Merger, net of treasury stock—  26,550 — — — — — —  
Return of common stock to pay withholding taxes on restricted stock—  — — (14,455)(150)— — — (150)
Issuance of common stock related to stock purchase agreement—  1,213,000 12 — — 6,987 — — 6,999 
Issuance of common stock related to service agreement—  11,459 — — — 75 — — 75 
Stock-based compensation—  — — — — 1,179 — — 1,179 
Foreign currency translation adjustment—  — — — — — (197)— (197)
Net loss—  — — — — — — (35,195)(35,195)
Balance as of December 31, 2023 $ 9,603,723 $96 (14,455)$(150)$153,827 $(197)$(142,203)$11,373 

The accompanying notes are an integral part of these consolidated financial statements.










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Consolidated Statements of Convertible Preferred Stock and Stockholders' Equity (Deficit)
(in thousands, except share amounts)

Total Convertible Preferred StockCommon StockTreasury Stock
Additional
Paid-in
Capital
Accumulated Other Comprehensive Loss
Accumulated
Deficit
Total
Stockholders'
Equity (Deficit)
SharesAmountSharesPar ValueSharesAmount
Balance as of December 31, 20211,408,100 $70,439 310,200 $3  $ $4,261 $ $(78,800)$(74,536)
Stock-based compensation— — — — — — 579 — — 579 
Issuance of common stock upon exercise of options— — 593 — — — — — 7 
Vesting of restricted common stock— — 9,488 — — — 13 — — 13 
Issuance of Series C convertible preferred stock, net of issuance costs of $1.2 million2,219,633 21,120 — — — — — — —  
Issuance of Series C convertible preferred stock upon extinguishment of convertible notes payable1,370,187 19,501 — — — — — — —  
Net loss— — — — — — — — (28,208)(28,208)
Balance as of December 31, 20224,997,920 $111,060 320,281 $3  $ $4,860 $ $(107,008)$(102,145)

The accompanying notes are an integral part of these consolidated financial statements.
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ELICIO THERAPEUTICS, INC.
Consolidated Statements of Cash Flows
(in thousands)

Year Ended December 31,
20232022
Cash flows from operating activities
Net loss$(35,195)$(28,208)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation382 390 
Amortization of right-of-use assets, operating leases788 667 
Non-cash interest expense1,061 3,596 
Change in fair value of embedded derivative(429)945 
Change in fair value of warrant liability— 
Stock-based compensation1,179 579 
Non-cash professional services expense75 — 
Gain on extinguishment of promissory notes(605)(2)
Loss on disposal of property and equipment105 
Changes in operating assets and liabilities:
Prepaid expenses and other current assets(729)(1,985)
Other long-term prepaid assets— 114 
Accounts payable23 1,125 
Accrued expenses and other current liabilities2,216 (305)
Deferred research obligation(742)1,436 
Operating lease liability(825)(535)
Net cash used in operating activities(32,694)(22,179)
Cash flows from investing activities
Purchases of property and equipment(66)(654)
Proceeds from sale of property and equipment34 — 
Net cash used in investing activities(32)(654)
Cash flows from financing activities
Cash acquired in connection with the reverse merger24,001 — 
Merger transaction costs(2,364)— 
Proceeds from issuance of promissory notes payable10,000 — 
Proceeds from issuance of Series C convertible preferred stock, net of issuance costs— 21,120 
Proceeds from issuance of common stock per purchase agreement6,999 
Payment for purchase of treasury stock(150)— 
Proceeds from exercise of stock options127 82 
Net cash provided by financing activities38,613 21,202 
Effect of foreign currency on cash— — 
Net increase (decrease) in cash, cash equivalents and restricted cash5,887 (1,631)
Cash, cash equivalents and restricted cash at the beginning of the year8,414 10,045 
Cash, cash equivalents and restricted cash at the end of the year$14,301 $8,414 
Components of cash, cash equivalents and restricted cash:
Cash and cash equivalents$12,894 $6,156 
Restricted cash1,407 2,258 
Total cash, cash equivalents and restricted cash$14,301 $8,414 
Supplemental disclosure of noncash investing and financing activities:
Loss on disposal of property and equipment$105 $
Non-cash issuance of Series C convertible preferred stock$— $19,501 
Settlement of promissory notes payable$10,027 $— 
Accretion of promissory note discount from embedded derivative$130 $— 
Accretion of promissory note to face value$897 $— 
Non-cash vesting of restricted common stock$67 $13 
Non-cash issuance of common stock from conversion of preferred stock$111,060 $— 
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Non-cash issuance of common stock to Angion stockholders$19,526 $— 
Non-cash issuance of common stock related to service agreement$75 $— 
Accretion of convertible note discount from embedded derivative$— $2,344 
Accretion of convertible note discount from issuance costs$— $328 
Interest expense from convertible notes payable$— $923 
The accompanying notes are an integral part of these consolidated financial statements.
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements


Note 1—Description of the Business and Financial Condition
Elicio Therapeutics, Inc. (“Elicio” or the “Company”) was incorporated in Delaware as Vedantra Pharmaceuticals Inc., in August 2011. Elicio is a clinical-stage biotechnology company developing a pipeline of novel immunotherapies for the treatment of cancer. In December 2018, Elicio formed a wholly-owned subsidiary, Elicio Securities Corporation (“ESC”), a Massachusetts corporation. ESC is an investment company. Elicio and ESC are collectively referred to as “Elicio” throughout these consolidated financial statements.
Reverse Merger Transaction
On January 17, 2023, the Company entered into a definitive merger agreement (the “Merger Agreement”) with Angion Biomedica Corp. (“Angion”), a clinical-stage biotechnology company, Arkham Merger Sub, Inc., a wholly owned subsidiary of Angion (“Merger Sub”), and Elicio Operating Company, Inc. (“Former Elicio”), pursuant to which Merger Sub merged with and into Former Elicio, with Former Elicio surviving the merger as a wholly owned subsidiary of Angion (the “Merger”).
On June 1, 2023, the Company completed the Merger in accordance with the terms and conditions of the Merger Agreement and Angion changed its name from “Angion Biomedica Corp.” to “Elicio Therapeutics, Inc.” Immediately following the consummation of the Merger, there were approximately 9.7 million shares of the Company’s common stock outstanding on a fully-diluted basis, with Former Elicio equity holders collectively owning approximately 65.2% of the Company and Angion equity holders collectively owning approximately 34.8% of the Company, in each case on a fully diluted basis.
The Merger was accounted for as a reverse recapitalization, with Former Elicio being treated as the acquirer for accounting purposes. See discussions of the transactions in connection with the Merger at Note 3 - Merger and Related Transactions.
Liquidity and Going Concern
The Company has experienced net losses and negative cash flows from operating activities since inception. As of December 31, 2023, the Company had an accumulated deficit of $142.2 million. The Company expects that its operating losses and negative operating cash flows will continue for the foreseeable future as the Company continues to develop its product candidates.
As of December 31, 2023, the Company had $12.9 million in cash and cash equivalentsequivalents. The Company’s losses from operations, negative operating cash flows and accumulated deficit, as well as the additional capital needed to fund operations for at least twelve months following the issuance of the consolidated financial statements, raise substantial doubt about the Company’s ability to continue as a going concern. The Company expects to incur substantial expenditures in the foreseeable future for the development of its product candidates and will require additional financing to continue this development. The Company plans to address this condition through the sale of Company common stock in public offerings and/or private placements, debt financings, or through other capital sources, including licensing arrangements, partnerships and collaborations with other companies or other strategic transactions, but there is no assurance these plans will be sufficientcompleted successfully or at all.If the Company is unable to meetobtain additional capital when and as needed to continue as a going concern, it might have to further reduce or scale back its operations and/or liquidate its assets, and the projected operating requirements well into 2023.values it receives for its assets in liquidation or dissolution could be significantly lower than the values reflected in its financial statements.

The accompanying consolidated financial statements have been prepared on a basis that assumes that the Company will continue as a going concern, which contemplates the realization of assets and satisfaction of liabilities in the normal course of business. The consolidated financial statements do not include any adjustments relating to the recoverability and classification of recorded asset amounts or the amounts and classification of liabilities that might be necessary should the Company be unable to continue as a going concern.
Note 2—Summary of Significant Accounting Policies
Basis of Presentation
The Company's consolidated financial statements have been prepared in conformity with accounting principles generally accepted in the United States of America ("GAAP"(“U.S. GAAP”). Any reference in these notes to applicable guidance is meant to refer to the authoritative accounting principles generally accepted in the United States as found in the Accounting Standard Codification (“ASC”) and Accounting Standards Updates (“ASU”) of the Financial Accounting Standards Board (“FASB”).
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

The consolidated financial statements include the accounts of the Company, its wholly owned subsidiary, Angion Biomedica Europe Limited, which was dissolved on March 16, 2021, and its wholly owned subsidiary, AngionElicio Australia Pty Ltd. (“Elicio Pty”), which was established on August 22, 2019.2019, and its wholly-owned subsidiary, ESC, which was established in Massachusetts in December 2018. The Company established AngionElicio Australia Pty, Ltd., an Australian subsidiary, for the purpose of qualifying for research credits for studies conducted in Australia.Australia and ESC is an investment company. All significant intercompany balances and transactions have been eliminated in consolidation.
Since Former Elicio was determined to be the accounting acquirer in connection with the Merger, for periods prior to the Merger, the consolidated financial statements were prepared on a stand-alone basis for Former Elicio and did not include the combined entities activity or financial position. Subsequent to the Merger, the consolidated financial statements as of and for the year ended December 31, 2023 include the acquired business from June 2, 2023 through December 31, 2023, and assets and liabilities at their acquisition date fair value. Historical share and per share figures of Former Elicio have been retroactively restated to reflect the impact of a reverse stock split completed in connection with and prior to the effective time of the Merger, based on the exchange ratio of 0.0181.
Segments
Operating segments are identified as components of an enterprise about which separate discrete financial information is available for evaluation by the chief operating decision-maker (“CODM”) in making decisions regarding resource allocation and assessing performance. The Company views its operations and manages its business as 1one operating segment. The Company has determined that the chief executive officer is the CODM.
Use of Estimates
The preparation of consolidated financial statements in conformity with GAAP requiresCompany’s management is required to make estimates and assumptions that affect the reported amounts of assets and liabilities and disclosure of contingent assets and liabilities at the datedates of the consolidated financial statements and the reported amounts of revenue and expenses during the reporting period. On an ongoing basis, management evaluates its estimates, including those related to the useful lives of long-lived assets, the measurement of stock-based compensation, change in fair value of warrant liabilities prior to IPO, accruals for research and development activities, income taxes and revenue recognition. The Company bases its estimates on historical experience and on other relevant assumptions that are reasonable under the circumstances. Actual results could materially differ from those estimates. Significant estimates reflected in these consolidated financial statements include but are not limited to, the accrual of research and development expenses, the valuation of stock-based awards, the operating right of use assets and operating lease liability, and going concern.
Foreign Currency Translation and Transactions
The United StatesAustralian Dollar (“USD”AUD”) is the functional currency for the Company’s operations outside the United States.Elicio Pty. Accordingly, nonmonetary assets and liabilities originally acquired or assumed in other currencies are recorded in USD at the exchange rates in effectAUD at the date they were acquired or assumed. Monetary assets and liabilities denominated in other currenciesAs part of the consolidation process, the Elicio Pty results are translated from AUD into the reporting currency of USD at the exchangeusing average rates infor profit and loss transactions and applicable spot rates for period-end balances. The effect at the balance sheet date. Translation adjustments are recorded in other comprehensive income (loss) in the consolidated statements of operations. Gains and losses realized from non-USD transactions, including intercompany balances not considered as permanent investments, denominated in currencies other than an entity’stranslating our functional currency are includedinto our reporting currency is reported separately in other income (expense) in the accompanying consolidated statements of operations.Accumulated Other Comprehensive Loss.
Concentrations of Credit Risk and Off-Balance Sheet Risk
Cash andFinancial instruments that potentially subject the Company to concentration of credit risk consist primarily of cash, cash equivalents, areand restricted cash. At times, cash balances deposited at major financial instruments that are potentially subject to concentrations of credit risk. The Company's cash and cash equivalents are deposited in accounts at large financialbanking institutions and amounts may exceed the federally insured limits.limit. The Company regularly monitors the financial condition of the institutions in which it has depository accounts and believes the risk of loss is minimal. The Company has not experienced any losses in such accounts and believes it is not exposed to significant risk on its cash balances due to the financial position of the depository institution in which those deposits are held.
Additionally, the Company established guidelines regarding approved investments and maturities of investments, which are designed to maintain safety and liquidity.
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ANGION BIOMEDICA CORP.
Notes to Consolidated Financial Statements (Continued)

The Company maintains its cash equivalents in securities and money market funds with original maturities less than three months.
The Company has no financial instruments with off-balance sheet risk of loss.accounts.
Cash and Cash Equivalents
The Company considers allCash and cash equivalents are comprised of deposits at major financial banking institutions and highly liquid investments with an original maturitiesmaturity of three months or less to be cash equivalents.at the date of purchase. As of December 31, 20212023 and 2020,2022, the Company’s cash equivalents were held in institutions in the United States and includedinclude deposits in a money market fund which were unrestricted as to withdrawal or use.
Grants ReceivableRestricted Cash
Grants receivable is comprisedRestricted cash consists of unbilled amounts due from various grants fromcash securing a collateral letter of credit issued in connection with the National Institutes of Health ("NIH")Company’s facility operating lease and other U.S. government agenciesa research grant. See Notes 6 and 11 for costs incurred prior to the period end under reimbursement contracts. All amounts are readily available for draw from the Federal Government Payment Management System and, accordingly, no allowance for doubtful amounts has been established. If amounts become uncollectible, they are charged to operations.further discussion.
Deferred Offering Costs
Deferred offering costs consist of legal and accounting fees incurred through the balance sheet date that were directly related to the Company's IPO and were reflected as issuance costs upon the completion of the offering. Subsequent to the closing of the IPO, $2.8 million of deferred costs previously included in prepaid expenses and other current assets were netted with additional paid in capital in the consolidated balance sheets. As of December 31, 2021 and 2020, the Company recorded deferred offering costs of zero and $2.0 million, respectively.
Property and Equipment
Property, equipment and leasehold improvements are stated at cost less accumulated depreciation and amortization. Depreciation and amortization is computed using the straight-line method over their estimated useful lives as follows:
Asset ClassificationEstimated Useful Life
Equipment5 years
Furniture and fixtures3 years
Leasehold improvementsShorter of useful life or lease term
Normal repairs and maintenance costs are expensed as incurred.
Impairment of Long-Lived Assets
Long-lived assets, such as property and equipment are reviewed for impairment whenever events or changes in circumstances indicate that the carrying amount of an asset may not be recoverable. If circumstances require a long-lived asset or asset group to be tested for possible impairment, the Company first compares undiscounted cash flows expected to be generated by that asset or asset group to its carrying value. If the carrying value of the long-lived asset or asset group is not recoverable on an undiscounted cash flow basis, an impairment is recognized to the extent that the carrying value exceeds its fair value. Fair value is determined through various valuation techniques including discounted cash flow models, quoted market values and third-party independent appraisals, as considered necessary. The impairment losses as of December 31, 2021 and 2020 were zero and $58 thousand, respectively.
Fair Value Measurement
Certain assets and liabilities are carried atThe Company follows the guidance prescribed by ASC Topic 820, Fair Value Measurements, which establishes a framework for measuring fair value, under GAAP. Fairand expands disclosures about fair value is determined using the principlesmeasurements. The standard provides a consistent definition of ASC 820, Fair Value Measurement. Fairfair value that focuses on an exit price which is described as the price that would be received to sell an asset or
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ANGION BIOMEDICA CORP.
Notes to Consolidated Financial Statements (Continued)

paid to transfer a liability in an orderly transaction between market participants at the measurement date. The fair value hierarchy prioritizes and defines the inputs to valuation techniques as follows:
Level 1:    Observable inputs such as quoted prices in active markets.
Level 2:    Inputs are observable for the asset or liability either directly or through corroboration with observable market data.
Level 3:    Unobservable inputs.
The inputs used to measure the fair value of an asset or a liability are categorized within levels of the fair value hierarchy. The fair value measurement is categorized in its entirety in the same level of the fair value hierarchy as the lowest level input that is significant to the measurement.
The Company's cash and cash equivalents, accounts payable and accrued expenses are carried at cost, which approximates fair value due to the short-term nature of these instruments.
Leases
The Company accounts for its leases under ASC 842, Leases. Under this guidance, arrangements meeting the definition of a lease are classified as operating or finance leases, and are recorded on the consolidated balance sheets as both a right of use asset and a lease liability, calculated by discounting fixed lease payments over the lease term at the rate implicit in the lease or the Company's incremental borrowing rate. Lease liabilities are increased by interest and reduced by payments each period, and the right of use asset is amortized over the lease term. For operating leases, interest on the lease liability and the amortization of the right of use asset results in straight-line rent expense over the lease term. Variable lease expenses are recorded when incurred.
In calculating the right of use assets and lease liabilities, the Company elects to combine lease and non-lease components. The Company excludes short-term leases having initial terms of 12 months or less from the new guidance as an accounting policy election, and recognizes rent expense on a straight-line basis over the lease term.
Investments in Related Party Entities
The Company holds a 10% and a 2.4% interest in 2 entities, NovaPark, LLC ("NovaPark") and Ohr Cosmetics, LLC ("Ohr"), respectively. There is common ownership between the Director and Chairman Emeritus of the Company and each entity, and our Chief Executive Officer is also owns approximately 0.80% of the membership interests in Ohr. See Note 15. In accordance with ASC 323, Investments —Equity Method and Joint Ventures, the Company has significant influence but not control over NovaPark as its ownership in the limited liability company exceeds 3-5%. Accordingly, the Company records the NovaPark investment under the equity method of accounting. The Ohr investment is recorded at cost.
Warrant Liability
The Company accounts for certain common stock warrants outstanding as a liability, in accordance with ASC 815, Derivatives and Hedging, at fair value and adjusts the instruments to fair value at each reporting period. This liability is subject to re-measurement at each reporting period until exercised, and any change in fair value is recognized in the consolidated statements of operations as a component of other income (expense). The fair value of the warrants issued by the Company has been estimated using a variant of the Black Scholes option pricing model. The underlying equity included in the Black Scholes option pricing model was valued based on the closing price of common stock at each measurement date.
Convertible Notes Payable at Fair Value
As permitted under ASC 825, Financial Instruments ("ASC 825"), the Company has elected the fair value option for recognition of its convertible notes. In accordance with ASC 825, the Company recognizes these convertible notes at fair value with changes in fair value recognized in the consolidated statements of operations. The fair value option may be applied instrument by instrument, but it is irrevocable. As a result of applying the fair value option, direct costs and fees related to the convertible notes were recognized in general and administrative
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ANGION BIOMEDICA CORP.ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

expense in earnings as incurred and not deferred.measurement date. The estimatedstandard establishes a three-level hierarchy for fair value measurements based on the nature of inputs used in the valuation of an asset or liability as of the convertible notes was determined by utilizing a present value cash flow model and the values of the equity underlying the conversion options were estimated using company equity values implied from the Subject Company Transaction Method which includes the back-solve and scenario-based methods (Probability Weighted Expected Return Method). See Note 4. Accrued interestmeasurement date.
Level 1:    Observable inputs such as unadjusted quoted prices in active markets for identical assets or liabilities at measurement.
Level 2:    Inputs (other than quoted prices included in Level 1) that are either directly or indirectly observable for the notes has been includedasset or liability. These include quoted prices for similar assets or liabilities in the changeactive markets and quoted prices for identical or similar assets or liabilities in fair value of convertible notes in the consolidated statements of operations. All outstanding convertible notes were converted into common stock upon the close of the IPO on February 9, 2021markets that are not active.
Level 3:    Unobservable inputs that are supported by little or no market activity and no balances remained outstanding as of December 31, 2021. See Note 6.
Convertible Preferred Stock
Series C convertible preferred stock included settlement features that result in liability classification. The initial carrying value of the Series C convertible preferred stock was accretedare significant to the settlement value, the fair value of the securities issued uponassets or liabilities.
To the conversionextent that valuation is based on models or inputs that are less observable or unobservable in the market, the determination of fair value requires more judgment. Accordingly, the degree of judgment exercised by the Company in determining fair value is greatest for instruments categorized in Level 3. A financial instrument’s level within the fair value hierarchy is based on the lowest level of any input that is significant to the fair value measurement.
The carrying amounts of financial instruments reflected in the consolidated balance sheets for cash and cash equivalents, current and non-current restricted cash, accounts payable, and accrued expenses approximate their respective fair values because of the Series C convertible preferred stock. The discountshort-term maturity of those financial instruments.
Property and Equipment
Property and equipment are recorded at cost and depreciated using the straight-line method over the estimated useful life of the asset. Upon sale or retirement, the cost and accumulated depreciation are eliminated from their respective accounts, and the resulting gain or loss is recorded in the consolidated statement of operations and comprehensive loss. Repair and maintenance expenditures are expensed as incurred. Construction in process is not depreciated until the asset is placed into service.
Asset ClassificationEstimated Useful Life
Equipment5 years
Furniture and fixtures3 years
Leasehold improvementsShorter of useful life or lease term
Impairment of Long-Lived Assets
Periodically, the Company evaluates its long-lived assets, which consist primarily of property and equipment, and right of use asset, for impairment whenever events or changes in circumstances indicate that the carrying amount of such assets may not be recoverable. Recoverability of assets to be held and used is measured by a comparison of the carrying amount of an asset to the settlementfuture undiscounted net cash flows expected to be generated by the asset. If such assets are considered to be impaired, the impairment to be recognized is measured by the amount by which the carrying amount of the asset exceeds the fair value of the asset. During the years ended December 31, 2023 and 2022, no impairments have occurred.
Derivative Financial Instruments
The convertible and promissory notes included embedded derivatives requiring bifurcation in accordance with ASC 815, Derivatives and Hedging. The valuation of the instruments was determined using widely accepted valuation techniques including the probability weighted expected return model. The fair value was accreteddetermined using a model with the assumptions for equity value proceeds, probability of occurrence of various liquidation scenarios, timeline to liquidity and risk-free interest expense using the effective interest method. During 2020, certain convertible notes were exchanged for Series C convertible preferred stock. As the exchange was accounted for as a modification, the Series C convertible preferred stock that was exchanged for the convertible notes was recorded atrate. The fair value and subject to re-measurementof the derivative instruments was measured at each reporting period prior to settlement on October 18, 2022, with gains and losseschanges in fair value reported through our consolidated statements of operations. All outstanding shares ofin earnings (loss).
Convertible Preferred Stock
Former Elicio had classified convertible preferred stock, par value $0.06 per share, (the “Preferred Stock”) as temporary equity in the accompanying consolidated balance sheets due to certain changes in control events that were converted into common stock upon the closeoutside of the Company’s IPO on February 9, 2021. See Note 7. AsFormer Elicio’s control, including sale or transfer of control of Former Elicio, as holders of the Preferred Stock could cause redemption of the shares in these situations. Former Elicio did not accrete the carrying values of the Preferred Stock to the redemption values since a liquidation event was not considered probable as of December 31, 2021, there was no convertible preferred stock outstanding.
Treasury Stock
The Company records the repurchase of shares of common stock at cost based on the settlement date2022. Subsequent adjustments of the transaction. These shares are classified as treasury stock, which iscarrying values to the ultimate redemption values would be made only if it becomes probable that such a reduction to stockholders' equity. Treasury stock is included in authorized and issued shares but excluded from outstanding shares. As ofliquidation event will occur. During the year ended December 31, 2021, all outstanding treasury shares were retired2023 an immaterial error was discovered in October 2021 upon approval by the Board of Directors.
Revenue
The Company does not have any products approved for sale and has not generated any revenue from product sales. The Company’s revenue to date has been primarily derived from government funding consisting of U.S. government grants and contracts, and revenue under its license agreements.
Contract Revenue
The Company accounts for revenue earned from contracts with customers under Accounting Standards Update ("ASU") No. 2014-09, Revenue from Contracts with Customers (Topic 606) ("ASC 606"). Under ASC 606, the Company recognizes revenue when a customer obtains control of promised goods or services, in an amount that reflects the consideration which the Company expects to receive in exchange for those goods or services. To determine revenue recognition for arrangements within the scope of ASC 606, the Company performs the following five steps:     
(1)    Identify the contract(s) with a customer;
(2)    Identify the performance obligations in the contract;
(3)    Determine the transaction price;
(4)    Allocate the transaction price to the performance obligations in the contract; and
(5)    Recognize revenue when (or as) the Company satisfies a performance obligation.
At contract inception, the Company assesses the goods or services promised within each contract, whether each promised good or service is distinct, and determines those that are performance obligations. The Company then recognizes as revenueFormer Elicio's 2022 audited financial statements whereas the amount of the transaction price that is allocated to the respective performance obligation when or as the performance obligation is satisfied.
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ANGION BIOMEDICA CORP.ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

The Company enters into agreements under which it may obtain upfront payments, milestone payments, royalty paymentsSeries A and other fees. Promises under these arrangements maySeries B Preferred Stock did not include research licenses, research services, including selection campaign research services for certain replacement targets,41,887 and 609,755 shares, respectively, that were deemed to be issued due to the obligation to share information duringantidilutive protection triggered by the research and the participation of alliance managers andSeries C shares issued in joint research committees, joint patent committees and joint steering committees. The Company assesses these promises within the contextOctober 2022 at a price below $1.00. As a result of the agreements to determine the performance obligations.Merger, all Former Elicio preferred stock were converted into Company common stock on June 1, 2023. See Note 7.
Licenses of Intellectual Property: If a license to its intellectual property is determined to be distinct from the other promises or performance obligations identified in the arrangement, the Company recognizes revenue from non-refundable, upfront fees allocated to the license when the license is transferred to the customer and the customer is able to use and benefit from the license. For licenses that are bundled with other promises, the Company utilizes judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, the appropriate method of measuring proportional performance for purposes of recognizing revenue from non-refundable, upfront payments. The Company evaluates the measure of proportional performance each reporting period and, if necessary, adjusts the measure of performance and related revenue recognition.
Milestone payments: The Company evaluates whether the regulatory and development milestones are considered probable of being reached and estimate the amounts to be included in the transaction price using the most likely amount method. The Company evaluates factors such as the scientific, clinical, regulatory, commercial and other risks that must be overcome to achieve the particular milestone in making this assessment. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price. At the end of each reporting period, the Company re-evaluates the probability of achievement of milestones and any related constraint, and if necessary, adjust the estimate of the overall transaction price.
Sales-based milestones and royalties: For sales-based royalties, including milestone payments based on the level of sales, the Company determines whether the sole or predominant item to which the royalties relate is a license. When the license is the sole or predominant item to which the sales-based royalty relates, the Company recognize revenue at the later of: (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied). To date, the Company has not recognized any sales-based royalty revenue resulting from any license agreement.
Deferred revenue, which is a contract liability, represents amounts received by the Company for which the related revenues have not been recognized because one or more of the revenue recognition criteria have not been met. The current portion of deferred revenue represents the amount expected to be recognized within one year from the consolidated balance sheet date based on the estimated performance period of the underlying performance obligation. The noncurrent portion of deferred revenue represents amounts expected to be recognized after one year through the end of the performance period of the performance obligation.
Grant RevenueIncome Taxes
The Company concluded that the Company's government grants are not within the scope of ASC Topic 606 as they do not meet the definition of a contract with a customer. The Company has concluded that the grants meet the definition of a contribution and are non-reciprocal transactions, and has also concluded that Subtopic 958-605, Not-for-Profit-Entities-Revenue Recognition, does not apply, as the Company is a business entity and the grants are with governmental agencies.
In the absence of applicable guidance under GAAP, the Company developed a policyprovides for the recognition of grant revenue when the allowable costs are incurred and the right to payment is realized.
The Company believes this policy is consistent with the overarching premise in ASC Topic 606, to ensure that revenue recognition reflects the transfer of promised goods or services to customers in an amount that reflects the consideration that the Company expects to be entitled to in exchange for those goods or services, even though there is no exchange as defined in ASC Topic 606. The Company believes the recognition of revenue as costs are incurred and amounts become realizable is analogous to the concept of transfer of control of a service over time under ASC Topic 606.
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ANGION BIOMEDICA CORP.
Notes to Consolidated Financial Statements (Continued)

Research and Development
Research and development costs include, but are not limited to, payroll and personnel expenses, laboratory supplies, preclinical studies, compound manufacturing costs, consulting costs and allocated overhead, including rent, equipment, depreciation and utilities. Research and development cost maybe offset by research and development refundable tax rebates received by our wholly-owned Australian subsidiary.
The Company has agreements with various Contract Research Organizations ("CROs") and third-party vendors. Research and development accruals of amounts due to the CRO are estimated based on the level of services performed, progress of the studies, including the phase or completion of events, and contracted costs. The estimated costs of research and development provided, but not yet invoiced, are included in accrued liabilities on the consolidated balance sheet. Payments made to CROs under such arrangements in advance of the performance of the related services are recorded as prepaid expenses and other current assets until the services are rendered. The Company makes judgments and estimates in determining the accrued expenses balance in each reporting period. As actual costs become known, the Company adjusts its accrued expenses. For the years ended December 31, 2021 and 2020, the Company has not experienced any material differences between accrued costs and actual costs incurred.
Advertising Costs
Advertising costs are expensed as incurred. For the years ended December 31, 2021 and 2020, advertising costs were not significant.
Stock-Based Compensation
The Company accounts for all stock-based payments to employees and non-employees, including grants of stock options, RSAs, RSUs, including "PSUs" to be recognized in the financial statements, based on their respective grant date fair values. The Company estimates the fair value of stock option grants using the Black-Scholes option pricing model. The RSAs, RSUs and PSUs are valued based on the fair value of the Company's common stock on the date of grant. The assumptions used in calculating the fair value of stock-based awards represent management's best estimates and involve inherent uncertainties and the application of management's judgment. The Company records expense for stock-based compensation related to stock options, RSAs and RSUs over the requisite service period. As the PSUs have a performance condition, compensation expense is recognized for each vesting tranche over the respective requisite service period of each tranche if and when the Company's management deems probable that the performance conditions will be satisfied. The Company may recognize a cumulative true-up adjustment related to PSUs once a condition becomes probable of being satisfied if the related service period had commenced in a prior period. All share-based compensation costs are recorded in general and administrative or research and development costs in the consolidated statements of operations based upon the respective employees or non-employee's roles within the Company. Forfeitures are recorded as they occur.
Income Taxes
Incomeincome taxes are recorded in accordance with ASC Topic 740, Income Taxes ("ASC 740"), which provides for deferred taxes using an asset and liability approach. The Company recognizes deferred tax assets and liabilities for the expected future tax consequences of events that have been included in the consolidated financial statements or tax returns.. Deferred tax assets and liabilities are determined based on the difference between the financial statementreporting and tax bases of assets and liabilities using enacted tax rates and laws in effect forin the yearyears in which the differences are expected to reverse. Valuation allowances areA valuation allowance is provided if, based upon the weight ofweighted available evidence, it is more likely than not that some or all of the deferred tax assets will not be realized.
The Company provides reserves for potential payments of tax to various tax authorities related to uncertain tax positions when the Company management determines that it is probable that a loss will be incurred related to these matters and the amount of the loss is reasonably determinable. The Company has not identified any significant uncertain tax positions as of December 31, 2023.
Research and Development
Research and development costs are charged to expense as incurred and consist of expenses incurred in performing research and development activities, including salaries and benefits, materials and supplies, preclinical expenses, stock-based compensation expense, depreciation of equipment, contract services, and other outside expenses. The Company accrues for costs incurred by external service providers, based on estimates of services performed and costs.These estimates include the level of services performed by the third parties, and other indicators of the services completed.Based on the timing of payments to service providers, the Company may also record prepaid expenses for those service providers that will be recognized as expenses in future periods as the related services are rendered. Research and development costs may be offset by research and development refundable tax rebates received by the Company’s wholly-owned Australian subsidiary.
Leases
ASU No. 2016-02, Leases (“ASC 842”) establishes a right-of-use model (“ROU”) that requires a lessee to recognize a ROU asset and corresponding lease liability on the balance sheet for all leases with a term longer than 12 months. Leases will be classified as finance or operating, with classification affecting the pattern and classification of expense recognition in the consolidated statements of operations as well as the reduction of the ROU asset.
At the inception of an arrangement, the Company determines whether the arrangement is or contains a lease based on specific facts and circumstances, the existence of an identified asset(s), if any, and the Company’s control over the use of the identified asset(s), if applicable. Operating lease liabilities and their corresponding ROU assets are recorded based on the present value of future lease payments over the expected lease term. The interest rate implicit in lease contracts is typically not readily determinable. As such, the Company will utilize the incremental borrowing rate, which is the rate incurred to borrow on a collateralized basis over a similar term an amount equal to the lease payments in a similar economic environment.
The Company has elected to combine lease and non-lease components as a single component. Operating leases are recognized on the consolidated balance sheet as ROU lease assets, current lease liabilities and non-current lease liabilities. Fixed rents are included in the calculation of the lease balances, while variable costs paid for certain operating and pass-through costs are excluded. Lease expense is recognized over the expected term on a straight-line basis.
Research Grant
The Company analogizes to the guidance provided by International Accounting Standards 20, Accounting for Government Grants and Disclosure of Government Assistance (“IAS 20”) for funds received from grants from entities that are not customers nor government agencies. The Company recognizes the amount of grant income based on the activity in allowable expenses covered under the grant and has elected to recognize the funds earned as an offset to the related research expenses recorded in operations. Advances from the grant that have yet to be recognized are recorded as restricted cash if the grant requires the funds to be isolated from general cash and cash equivalents. The Company records a liability for any research activity that is required under the grant but has not yet been performed. The liability is recorded as deferred research obligation on the consolidated balance sheets.
Stock-Based Compensation
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Notes to Consolidated Financial Statements (Continued)

The Company issues stock-based awards to employees and non-employees, generally in the form of stock options. The Company accounts for uncertain tax positionsstock-based awards in accordance with ASC 718, Compensation—Stock Compensation, which requires all stock-based payments, to be recognized in the consolidated statements of operations based on their fair values. The expense is recognized on a straight line basis over the requisite service period, which is generally the vesting period. The Company has elected to account for option forfeitures as they occur.
The Company uses the Black-Scholes option-pricing model (“Black-Scholes”) to determine the weighted-average fair value of options granted, which uses as inputs the fair value of the Company common stock, assumptions the Company makes for the volatility of its Company common stock, the expected term of its stock options, the risk-free interest rate for a period that approximates the expected term of its stock options and its expected dividend yield.
Compensation cost of awards that contain a performance condition are recognized when success is considered probable during the performance period.
Prior to the Merger, there was no public market for Former Elicio’s common stock. The estimated fair value of the Company’s common stock underlying Former Elicio’s stock-based awards was determined by Former Elicio’s board of directors as of the grant date of each option grant. To determine the fair value of Former Elicio’s common stock underlying option grants, Former Elicio’s board of directors considered, among other things, input from management and valuations of Former Elicio's common stock prepared by third-party valuation firms performed in accordance with the provisionsguidance outlined in the American Institute of ASC 740. When uncertain tax positions exist,Certified Public Accountants' Accounting and Valuation Guide, Valuation of Privately-Held-Company Equity Securities Issued as Compensation. Following the Company recognizesMerger, the tax benefitfair value of tax positions to the extent that the benefit would more likely than not be realized assuming examination by the taxing authority. The determination as to whether the tax benefit will more likely than not be realizedCompany’s common stock is based uponon the technical meritsclosing stock price on the date of grant as reported on the tax position as well as consideration of the available facts and circumstances. To date, there have been no interest or penalties charged in relation to the unrecognized tax benefits.Nasdaq Global Select Market.
Net Loss Per Share
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Notes to Consolidated Financial Statements (Continued)

Basic net loss per share of Company common stock is computed by dividing net loss attributable to Company common stockholders by the weighted average number of shares of Company common stock outstanding for the period. Diluted net loss per share excludes the potential impact of convertible preferred stock,Company common stock options, warrants and unvested shares of restricted stock and restricted stock units because their effect would be anti-dilutive due to the Company's net loss. Since the Company had net losses for the years ended December 31, 20212023 and 2020,2022, basic and diluted net loss per common share are the same.
Comprehensive Loss
Comprehensive loss represents the net loss for theis defined as a change in equity during a period from transactions and other comprehensive income. Other comprehensive income reflects certain gainsevents and losses that are recorded as a component of stockholders’ deficit and are not reflected in the statements of operations. The Company’s other comprehensive income consists of foreign currency translation adjustments.circumstances from non-owner sources.
Recently Adopted Accounting Pronouncements
In August 2020, the FASB issued ASU No. 2020-06, Debt-Debt with Conversion and Other Options (Subtopic 470-20) and Derivatives and Hedging-Contracts in Entity's Own Equity (Subtopic 815-40): Accounting for Convertible Instruments and Contracts in an Entity's Own Equity, which simplifies accounting for convertible instruments by removing major separation models required under current U.S. GAAP. ASU No. 2020-06 removes certain settlement conditions that are required for equity contracts to qualify for the derivative scope exception and it also simplifies the diluted earnings per share calculation in certain areas. This guidance is effective for fiscal years, and interim periods within those fiscal years, beginning after December 15, 2021. Early adoption is permitted for fiscal years, and interim periods within those fiscal years, beginning after December 15, 2020. The Company adopted this standard as of January 1, 2021, which did not have material impact on its consolidated financial statements and related disclosures.
In December 2019, the FASB issued ASU No. 2019-12, Income Taxes (Topic 740)-Simplifying the Accounting for Income Taxes (ASU 2019-12), which is intended to simplify accounting for income taxes. It removes certain exceptions to the general principles in Topic 740 and amends existing guidance to improve consistent application. ASU 2019-12 was effective for the Company for fiscal years beginning after December 15, 2020, including interim periods therein. The Company adopted this standard as of January 1, 2021, which did not have material impact on its consolidated financial statements and related disclosures.
In January 2020, the FASB issued ASU No. 2020-01, Investments-Equity Securities (Topic 321), Investments-Equity Method and Joint Ventures (Topic 323), and Derivatives and Hedging (Topic 815)-Clarifying the Interactions between Topic 321, Topic 323, and Topic 815 (a consensus of the Emerging Issues Task Force). This update clarifies whether an entity should consider observable transactions that require it to either apply or discontinue the equity method of accounting for the purposes of applying the measurement alternative and how to account for certain forward contracts and purchased options to purchase securities. For public entities, this guidance was effective for fiscal years beginning after December 15, 2020. The Company adopted this standard as of January 1, 2021, which did not have material impact on its consolidated financial statements and related disclosures.
In October 2020, the FASB issued ASU No. 2020-10, Codification Improvements. ASU 2020-10 provides amendments to a wide variety of topics in the FASB’s Accounting Standards Codification, which applies to all reporting entities within the scope of the affected accounting guidance. ASU 2020-10 was effective for the Company for fiscal years beginning after December 15, 2020, including interim periods therein. The Company adopted this standard as of January 1, 2021, which did not have material impact on its consolidated financial statements and related disclosures.
In November 2021, the FASB issued Accounting Standards Update (ASU) 2021-10, Government Assistance (Topic 832): Disclosures by Business Entities about Government Assistance. ASU 2021-10 requires business entities to disclose, in notes to their financial statements, information about certain types of government assistance they receive. ASU 2021-10 also adds a new Topic 832, Government Assistance, to the FASB’s Codification. ASU 2021-10 is effective for financial statements of all entities, including private companies, for annual periods beginning
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ANGION BIOMEDICA CORP.
Notes to Consolidated Financial Statements (Continued)

after December 15, 2021, with early application permitted. The Company adopted this standard as of January 1, 2021, which did not have material impact on its consolidated financial statements and related disclosures.

Recently Issued Accounting Pronouncements Not Yet Adopted
In June 2016, the FASB issued ASU No. 2016-13, Financial Instruments—Credit Losses (Topic 326) Measurement of Credit Losses on Financial Instruments (ASU (“ASU No. 2016-13)2016-13”), which requires an entity to utilize a new impairment model known as the current expected credit loss (“CECL”) model to estimate its lifetime “expected credit loss” and record an allowance that, when deducted from the amortized cost basis of the financial assets and certain other instruments, including but not limited to, available-for-sale debt securities. Credit losses relating to available-for-sale debt securities will be recorded through an allowance for credit losses rather than as a direct write-down to the security. As an emerging growth company, ASU No. 2016-13 is effective for the Company for fiscal years beginning after December 15, 2022, with early adoption permitted. The Company is currently evaluating the impact of the adoption ofadopted ASU No. 2016-13 on January 1, 2023 and the adoption of the standard had no material impact on its consolidated financial statements.

In August 2020, the FASB issued ASU No. 2020-06,
Note 3—RevenueDebt - Debt with Conversion and Deferred Revenue
Grant Revenue
Our grantsOther Options (Subtopic 470-20) and Derivatives and Hedging - Contracts in Entity’s Own Equity (Subtopic 815-40) - Accounting for Convertible Instruments and Contracts in an Entity’s Own Equity (“ASU No. 2020-16”), which simplifies the accounting for certain financial instruments with characteristics of liabilities and equity, including convertible instruments and contracts reimburse us for directon an entity’s own equity. The Company adopted ASU No. 2020-06 on January 1, 2023 and indirect costs relating to the grant projects and also provide us with a pre-negotiated profit margin on total direct and indirect costsadoption of the grant award, excluding subcontractor costs, after giving effectstandard had no material impact on its consolidated financial statements.
Recently Issued Accounting Standards Not Yet Adopted
From time to directly attributable coststime, new accounting pronouncements are issued by the FASB or other standard setting bodies and allowable overhead costs. Funds received from grants and contracts are generally deemed to be earned and recognized as revenue as allowable costs are incurred during the grant or contract period and the right to payment is realized.
For the years ended December 31, 2021 and 2020,adopted by the Company recognized grant revenueas of $0.8 million and $2.7 million, respectively.
Contract Revenue

The Company’s contract revenue has been generated from payments received pursuant to a license agreement (the "Vifor License") with Vifor International, Ltd. ("Vifor Pharma") with headquarters located in Switzerland. The Company recognized revenue from upfront payments over the term of our estimated period of performance using a cost-based input method under Topic 606. The Company expects to continue recognizing revenue from upfront payments related to the Vifor License using the cost-based input method.
Vifor License Agreement

In November 2020,specified effective date. Except as noted below, the Company entered intobelieves that the impact of recently issued standards that are not yet effective will not have a license agreement with Vifor Pharma, granting Vifor Pharma global rights (excluding China, Taiwan, Hong Kongmaterial impact on its consolidated financial statements and Macau) to develop, manufacture and commercialize ANG-3777 in all therapeutic, prophylactic and diagnostic uses for renal indications, including forms of acute kidney injury (AKI), and congestive heart failure (collectively, the Renal Indications). Pursuant to the Vifor License, the Company received $60 million in upfront and equity payments, including $30 million in up-front cash received in November 2020, and a $30 million equity investment, $5 million of which was a convertible note that subsequently converted into common stock with the IPO and $25 million of which was received in the Concurrent Private Placement with the Company’s IPO. The Company is also eligible to receive post-approval milestones of up to approximately $260.0 million and sales-related milestones of up to $1.585 billion, providing a total potential deal value of up to $1.925 billion (subject to certain specified reductions and offsets), plus tiered royalties on net sales of ANG-3777 at royalty rates of up to 40%. Under the Vifor License, the Company is responsible for executing a pre-specified clinical development plan designed to obtain regulatory approvals of ANG-3777 for delayed graft function (DGF) and AKI associated with cardiac surgery involving cardiopulmonary bypass (CSA-AKI). Based on the ANG-3777 clinical trial data disclosed in the fourth quarter of 2021, the Company does not expect to receive anydisclosures.
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Notes to Consolidated Financial Statements (Continued)

In November 2023, the FASB issued No. 2023-07, Segment Reporting (Topic 280): Improvements to Reportable Segment Disclosures. This ASU broadens the disclosure requirements by requiring disclosures of significant segment expenses that are regularly provided to the CODM and included within each reported measure of segment profit or loss. The standard also requires entities to disclose, on an interim and annual basis, the amount and description, including the nature and type, of the other segment items. Additionally, entities are required to disclose the title and position of the individual identified as the CODM and an explanation of how the CODM uses the reported measures of a segment’s profit or loss in assessing segment performance and deciding how to allocate resources. These enhanced disclosure obligations apply to entities that operate with one reportable segment as well. ASU 2023-07 is effective for fiscal years beginning after December 15, 2023, and interim periods within fiscal years beginning after December 15, 2024 on a retrospective basis. Early adoption is permitted. We are currently assessing the impact that this new accounting standard will have on our consolidated financial statements and disclosures.
In December 2023, the FASB issued ASU No. 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures. This ASU requires disaggregated information about a reporting entity’s effective tax rate reconciliation as well as additional clinical, post-approval, or sales milestones, or royalties, asinformation on income taxes paid. The standard requires entities to disclose federal, state, and foreign income taxes in their rate reconciliation tables and elaborate on reconciling items that exceed a quantitative threshold. Additionally, it does not intend to continue to pursue the clinical development planrequires an annual disclosure of income taxes paid, net of refunds, categorized by jurisdiction based on a quantitative threshold. The ASU is effective on a prospective basis for ANG-3777 set forthannual periods beginning after December 15, 2024. Early adoption is permitted. This ASU will result in the Vifor License.required additional disclosures being included in our consolidated financial statements, once adopted.
Note 3—Merger and Related Transactions

On October 26, 2021,As described in Note 1, Former Elicio merged with a wholly owned subsidiary of Angion on June 1, 2023. The Merger was accounted for as a reverse recapitalization under U.S. GAAP. Former Elicio was considered the Company announcedaccounting acquirer for financial reporting purposes. This determination was based on the facts that, its Phase 3 trial of ANG-3777 in DGF did not achieve its primary endpoint andimmediately following the data from the Phase 3 trial was not expected to provide sufficient evidence to support an indication in the studied DGF population. On December 9, 2021, the Company announced its Phase 2 trial of ANG-3777 in CSA-AKI did not achieve its primary endpoint and the data from the Phase 2 trial was not expected to provide sufficient evidence to supportMerger: (i) Former Elicio stockholders own a Phase 3 trial in the studied CSA-AKI population. Angion and Vifor continue to analyze data from the CSA-AKI trial. The Company does not intend to continue the clinical development plan for ANG-3777 set forth in the Vifor License, which had included a Phase 3 study in CSA-AKI and a Phase 4 confirmatory study in DGF. In 2022, we and Vifor Pharma continue to work to complete the planned analysessubstantial majority of the resultsvoting rights; (ii) Former Elicio designated a majority (six of nine) of the clinical trials announced in the fourth quarter of 2021 and to discuss the future of the collaboration based upon such analyses.
Vifor Pharma may terminate the Vifor License at its sole discretion upon the earlier of (i) the acceptance for filing of an NDA covering products incorporating ANG-3777 filed with the FDA (after completion of the relevant Phase 3 clinical trial for such products), or (ii) the third anniversary of the effective date of the Vifor License. Both the Company and Vifor Pharma may terminate the Vifor License in its entirety if the other is in material breach of the Vifor License and has not cured the breach (if curable) within 60 days, or 90 days for incurable breach. In certain circumstances, in the eventinitial members of the Company’s material breachboard of directors of the Vifor License, Vifor Pharma may terminatecombined company; (iii) Former Elicio’s executive management team became the Vifor Licensemanagement team of the combined company; and (iv) the Company was named Elicio Therapeutics, Inc. and is headquartered in Boston, Massachusetts. Accordingly, for accounting purposes, the Merger was treated as the equivalent of Former Elicio issuing stock to acquire the net assets of Angion. As a result of the Merger, the net assets of Angion were recorded at their acquisition-date fair value, which approximated book value due to the short-term nature of the instruments, in the financial statements of Former Elicio and the reported operating results prior to the Merger were those of Former Elicio. Historical common share amounts of Former Elicio have been retroactively restated based on the exchange ratio of 0.0181 (the “Exchange Ratio”). It was concluded that any in-process research and development assets that remained as of the Merger would be de minimis when compared to the cash and investments obtained through the Merger.
Prior to the effective time of the Merger, on June 1, 2023, in connection with respectthe transactions contemplated by the Merger Agreement, the Company effected a reverse stock split of Angion’s common stock, par value $0.01 per share (“Angion common stock”), at a ratio of 10:1 (the “Reverse Stock Split”). At the effective time of the Merger, each outstanding share of Former Elicio capital stock (after giving effect to certain major markets. In addition, both parties havethe automatic conversion of all shares of Former Elicio preferred stock into shares of Former Elicio common stock and excluding any shares held as treasury stock by Former Elicio or held or owned by Angion or any subsidiary of Angion or Former Elicio and any dissenting shares) was converted into the right to terminatereceive 0.0181 shares of Angion common stock, which resulted in the Vifor License upon insolvencyissuance by Angion of an aggregate of 5,375,751 shares of Angion common stock to the stockholders of Former Elicio (the “Exchange Shares”), and a total of 8,387,025 shares of the other party.
The Company identifiedcommon stock being issued and outstanding immediately following the following performance obligations in the Vifor License based upon the clinical development plan for ANG-3777: (1) the global license (excluding greater China), (2) the development services, including the clinical development services including a post-approval confirmatory study, the technical development services and regulatory services and (3) the required participation on Joint Committees for coordination and oversight. The Company determined that the license is not capable of being distinct due to the specialized natureeffective time of the development servicesMerger. In addition, Angion assumed the Elicio 2022 Equity Incentive Plan and the Elicio 2012 Equity Incentive Plan (the “Elicio Plans”) and each outstanding and unexercised option to be provided bypurchase Former Elicio common stock and each outstanding and unexercised warrant to purchase Former Elicio capital stock were adjusted with such stock options and warrants henceforth representing the Company, and, accordingly, this promise was combined with the development services and participation in the joint committees as one single performance obligation.
In orderright to determine the transaction price, the Company evaluated all the payments to be received during the durationpurchase a number of the contract. Certain milestones and additional fees were considered variable consideration, which were not included in the transaction price at contract inception. The Company determined that the transaction price at the inception of the Vifor License is $15.0 million, which is 50% of the $30.0 million upfront payment due to the potential setoff defined in the contract. The Company will re-evaluate the transaction price in each reporting period and as uncertain events are resolved or other changes in circumstances occur.
In the fourth quarter of 2021, the Company reported topline results from two ANG-3777 clinical trials under the Vifor License. The Company determined it will no longer continue the current clinical development plan for ANG 3777 DGF and CSA-AKI, which had included a Phase 3 study for CSA-AKI and a Phase 4 confirmatory study in DGF, given neither trial achieved statistical significance on its primary endpoint. In connection therewith, the Company adjusted the transaction price to include $15.0 million in previously constrained variable consideration. As of December 31, 2021, the Company concluded that it has significantly satisfied the performance obligation under Vifor License and will fully conclude the ANG-3777 project by the end of 2022.
Using the cost-based input method, the Company recognizes revenue based on actual costs incurred as a percentage of total estimated costs as the Company completes its performance obligation. The cumulative effect of revisions to estimated costs to complete the Company’s performance obligation will be recorded in the period in which changes are identified and amounts can be reasonably estimated. These actual costs consist primarily of internal full time equivalent (FTE) efforts and third-party contract costs related to the Vifor License.
The Company reassessed the performance period as the Company is currently closing out the planned analyses from both trials but does not intend to continue the clinical development plan for ANG-3777 set forth in the Vifor License, which had included a Phase 3 study for CSA-AKI and a Phase 4 confirmatory study in DGF, given these clinical results. As such, the estimated date to fully conclude ANG-3777 by the end of December 2022 was determined to represent the completionshares of the Company’s performance obligation undercommon stock equal to the Vifor License. Additionally,Exchange Ratio multiplied by the Company revisednumber of shares of Former Elicio common stock previously represented by such options, and warrants at an exercise price equal to the total estimated costs for completionexercise price of Former Elicio capital stock divided by the Exchange Ratio.
In connection with execution of the performance obligationMerger Agreement, Angion made a bridge loan to reflectFormer Elicio pursuant to a note purchase agreement and promissory notes up to an aggregate principal amount of $12.5 million, issued with a 20% original issue discount, with an initial closing held substantially concurrently with the execution of the Merger Agreement for a principal amount of $6.25 million on account of a $5.0 million loan and an additional closing for a
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Notes to Consolidated Financial Statements (Continued)

the winding downprincipal amount of ANG-3777-related studies. The performance period is expected$6.25 million on account of a $5.0 million loan upon delivery by Former Elicio to end in the fourth quarterAngion of 2022 instead of the fourth quarter of 2026. The effect of this change in estimate was an increase in contract revenue by $24.2 million, a reduction in net loss by $24.2 million and an increase in basic and diluted earnings per share by $0.86Former Elicio’s audited financial statements for the year ended December 31, 2021.2022.
ForAs part of the yearsrecapitalization, the Company obtained the assets and liabilities listed below (in thousands):

Cash and cash equivalents$24,001 
Other current assets540 
Promissory notes10,027 
Accrued liabilities(2,438)
Net assets acquired$32,130 

Per the terms of the Merger Agreement, upon completion of the Merger, all obligations owed by Former Elicio related to the promissory notes were automatically forgiven and the amount advanced by Angion, along with any accrued and unpaid interest, was credited towards the net cash balance used to calculate the assets and liabilities listed above. Upon settlement of the promissory notes, the Company recognized a gain of $0.6 million related to extinguishment of the promissory notes.
The Company recognized the net assets acquired, excluding the promissory notes and transaction costs of $2.9 million, as an increase to additional paid-in capital in the consolidated statements of convertible preferred stock and stockholders’ equity (deficit) for the year ended December 31, 2021 and 2020, the Company recognized license revenue related to the Vifor License of $27.5 million and $0.2 million. As of December 31, 2021, $2.3 million was recorded as the current portion of deferred revenue on the consolidated balance sheet related to the Vifor License. As of December 31, 2020, $29.8 million was recorded as deferred revenue on the consolidated balance sheet related to the Vifor License.

2023.
Note 4—Fair Value Measurements
The following table classifiestables present the Company's financial assets and liabilities measured at fair value on a recurring basis intoand their assigned levels within the fair value hierarchy as of December 31, 2021 and 2020 (in thousands):
Fair Value Measured at December 31, 2021
Quoted Prices in
Active Markets for
Identical
Assets (Level 1)
Significant
Other
Observable
Inputs (Level 2)
Significant
Unobservable
Inputs (Level 3)
Total
Assets included in:
Cash and cash equivalents—Money market securities (1)
$87,252 $— $— $87,252 
Total fair value$87,252 $— $— $87,252 
Liabilities included in:
Warrants$— $— $114 $114
Total fair value$— $— $114 $114 
Fair Value Measured at December 31, 2023
Quoted Prices in
Active Markets for
Identical
Assets (Level 1)
Significant
Other
Observable
Inputs (Level 2)
Significant
Unobservable
Inputs (Level 3)
Total

Money market funds (1)
$5,973 $— $— $5,973 
Total assets$5,973 $— $— $5,973 

Warrant liabilities$— $— $11 $11 
Total Liabilities$— $— $11 $11 

Fair Value Measured at December 31, 2020
Quoted Prices in
Active Markets for
Identical
Assets (Level 1)
Significant
Other
Observable
Inputs (Level 2)
Significant
Unobservable
Inputs (Level 3)
Total
Assets included in:
Cash and cash equivalents—Money market securities (1)
$$— $— $
Total fair value$$— $— $
Liabilities included in:
Convertible notes$— $— $51,170 $51,170 
Warrants— — 10,704 10,704 
Series C convertible preferred stock— — 2,518 2,518 
Total fair value$— $— $64,392 $64,392 
Fair Value Measured at December 31, 2022
Quoted Prices in
Active Markets for
Identical
Assets (Level 1)
Significant
Other
Observable
Inputs (Level 2)
Significant
Unobservable
Inputs (Level 3)
Total

Money market funds (1)
$5,340 $— $— $5,340 
Total assets$5,340 $— $— $5,340 
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Notes to Consolidated Financial Statements (Continued)

___________________
(1) Included in cash and cash equivalents on the consolidated balance sheets. This balance includes cash requirements settled on a nightly basis.
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Notes to Consolidated Financial Statements (Continued)

Cash equivalents at December 31, 2023 and 2022 were held in U.S. Treasury Securities.
There were no transfers made among the three levels in the fair value hierarchy during periods presented.
As part of the Merger transaction, Former Elicio adopted Angion’s warrant liabilities. The following table presents a summary of changes in Level 3 liabilities measured atin the fair value of the Company’s common stock warrant liability (in thousands):
Warrant
Liability
Convertible
Notes
Series C Convertible Preferred Stock at Fair ValueTotal
Balance—December 31, 2020$10,704 $51,170 $2,518 $64,392 
Conversion of convertible Series C convertible preferred stock into common stock(6,110)(6,110)
Conversion of convertible notes into common stock(58,639)(58,639)
Net exercise of warrants(13,509)(13,509)
Change in fair value2,919 7,469 3,592 13,980 
Balance—December 31, 2021$114 $ $ $114 
As of December 31, 2023As of December 31, 2022
Balance, beginning of year$— $— 
Existing Angion Warrant Liability— 
Change in fair value— 
Balance, end of year$11 $— 
Both observable and unobservable inputs were used to determine the fair value of positions that the Company has classified within the Level 3 category. Unrealized gains and losses associated with assets and liabilities within the Level 3 category include changes in fair value that were attributable to both observable (e.g., changes in market interest rates) and unobservable (e.g., changes in unobservable long- datedlong-dated volatilities) inputs.
The Company used an option model to measure the fair value of the Notes (on conversion date). The values of the equity underlying the conversion options in the model were estimated using equity values implied from sales of convertible preferred stock. The fair value of the Notes was impacted by the model selected as well as assumptions surrounding unobservable inputs. Key unobservable inputs include the expected volatility of the underlying equity, and the timing of an expected liquidity event.
The fair value of the warrants issued by the Company has been estimated using a variant of the Black Scholes option pricing model.Black-Scholes. The underlying equity included in the Black Scholes option pricing modelBlack-Scholes was valued based on the equity value implied from sales of preferred and common stock at each measurement date. The fair value of the warrants was impacted by the model selected as well as assumptions surrounding unobservable inputs including the underlying equity value, expected volatility of the underlying equity, risk free interest rate, and the expected term.
Convertible NotesThe Company records the change in the fair value of common stock warrants in change in fair value of warrant liability in the consolidated statements of operations.
The fair value adjustment during the year ended December 31, 2021 was based on the final settlement amount using a conversion price of $11.57 per share on February 9, 2021. Subsequent to the closing of the IPO, therecommon stock warrant liability was estimated using the following assumptions:
December 31, 2023June 1, 2023
Strike price$76.00 $76.00 
Contractual term (years)4.75.2
Volatility (annual)94.0 %100.0 %
Risk-free rate3.9 %3.9 %
Dividend yield (per share)0.0 %0.0 %

Note 5—Balance Sheet Components
Prepaid and Other Current Assets
Prepaid and other current assets were no convertible notes outstanding.
Series C Preferred Stock
The fair value adjustment during the year ended December 31, 2021 was based on the final settlement amount using a conversion price of $11.57 per share on February 9, 2021. Subsequent to the closingcomprised of the IPO, there were no shares of convertible preferred stock outstanding.following (in thousands):
Warrant Liability
The fair value adjustment for the net exercise of warrants with an exercise price of $6.43 during the year ended December 31, 2021 was based on the final settlement amount using the IPO price on February 9, 2021. Subsequent to the closing of the IPO, the fair value of the warrants issued by the Company were estimated using a variant of the Black Scholes option pricing model. The underlying equity included in the Black Scholes option pricing model was valued based on the closing price of common stock at each measurement date.
December 31,
20232022
Prepaid research and development contract services$1,883 $2,132 
Advanced professional fees300 648 
Prepaid insurance376 104 
Other prepaid expenses and other current assets173 36 
Total prepaid and other current assets$2,732 $2,920 
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ANGION BIOMEDICA CORP.ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

During the years ended December 31, 2021 and 2020, the fair value of the warrants increased by $2.9 million and $4.9 million, respectively. The change in fair value of warrant liability in both periods was recognized in the consolidated statements of operations.
A summary of the weighted average (in aggregate) significant unobservable inputs (Level 3 inputs) used in measuring the Company's warrant liabilities that were categorized within Level 3 of the fair value hierarchy as of December 31, 2021 and 2020 was as follows:
December 31,
20212020
Strike price$8.01 $9.18 
Contractual term (years)1.24.9
Volatility (annual)74.6 %86.8 %
Risk-free rate0.7 %0.1 %
Dividend yield (per share)0.0 %0.0 %

Note 5—Balance Sheet Components
R&D tax credit receivable
The Company also recorded an Australian tax credit as provided by the Australian Taxation Office for qualified research and development expenditures incurred through its subsidiary, Savara Australia Pty. Limited. Under Australian tax law, Australia remits a research and development tax credit equal to 43.5% of qualified research and development expenditures, not to exceed established thresholds. During the year ended December 31, 2021, the Company generated an Australian tax credit of $0.8 million which was included in prepaid expenses and other current assets on the consolidated balance sheets and the Company received the tax credit in January 2022.
Property and Equipment, Net
The Company's property and equipment, net was comprised of the following (in thousands):
December 31,
20212020
December 31,December 31,
202320232022
EquipmentEquipment$866 $512 
Furniture and fixturesFurniture and fixtures34 27 
Leasehold improvementsLeasehold improvements68 43 
Total property and equipmentTotal property and equipment968 582 
Less: accumulated depreciationLess: accumulated depreciation(517)(426)
Property and equipment, netProperty and equipment, net$451 $156 
Depreciation expense for the years ended December 31, 20212023 and 20202022 was $0.1 million.$0.4 million and $0.4 million, respectively.
Other Long-term Prepaid Assets
Other long-term prepaid assets consisted of the advanced payments for clinical trial services, totaling $2.8 million for the years ended December 31, 2023 and 2022.
Accrued Expenses
Accrued expenses consisted of the following (in thousands):
December 31,
20232022
Accrued professional fees$945 $180 
Accrued compensation and benefits1,849 1,491 
Accrued research and development912 260 
Other accrued expenses51 
Total accrued expenses$3,757 $1,935 
Note 6—Research Grant
In September 2022, Former Elicio entered into a grant agreement with the Gastro-Intestinal (“GI”) Research Foundation, a not-for-profit organization focused on supporting research to treat, cure and prevent digestive diseases. Of the $2.8 million award, $2.3 million was received in September 2022 and the remaining $0.5 million was received in June 2023 with the completion of the development efforts as defined in the agreement. The final $0.5 million payment was applied as a credit to the second grant agreement described below. For the years ended December 31, 2023 and 2022, the Company incurred $1.9 million and $0.9 million in research and development expenses related to this project.
In September 2023, the Company entered into a second grant agreement with the GI Research Foundation for $3.1 million, with such amount received net of a $0.5 million credit. The grant funds available as of December 31, 2023 are $0.7 million, which are reflected in restricted cash and the deferred research obligation in the accompanying consolidated balance sheets. For the year ended December 31, 2023, the Company incurred $1.9 million in research and development expenses related to this project.
The award money for both agreements was earned and recognized as a contra research and development expense as the expenses were incurred.
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ANGION BIOMEDICA CORP.ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

PrepaidNote 7—Convertible Preferred Stock, Common Stock and Other Current AssetsStockholders' Equity
PrepaidAuthorized Shares
The Company's current Amended and other current assets were comprisedRestated Certificate of Incorporation, as amended, authorizes 300,000,000 shares of common stock, par value $0.01 per share, and 10,000,000 shares of preferred stock, par value $0.01 per share.
Convertible Preferred Stock of Former Elicio
Former Elicio’s convertible preferred stock consisted of Series A preferred stock (“Series A Preferred Shares”), Series B preferred stock (“Series B Preferred Shares”) and Series C preferred stock (“Series C Preferred Shares”).
Series C Convertible Preferred Stock
In May 2022, Former Elicio authorized the sale and issuance of up to 760,200 shares of $0.06 par value Series C Preferred Shares at an original issuance price of $66.30 per share and up to 325,800 shares of Series C Preferred for the settlement of the following (in thousands):convertible notes payable. The Series C Preferred Shares financing was structured to be issued in rolling closes in 2022.
December 31,
20212020
Deferred Offering costs$— $1,978 
Prepaid clinical fees168 — 
Business insurance275 — 
Security deposit131 — 
Convertible note receivable— 5,000 
Angion Pty tax863 352 
Other248 360 
Total prepaid and other current assets$1,685 $7,690 
Accrued Expenses
Accrued expenses were comprisedIn October 2022, Elicio increased the authorized number of Series C Preferred Shares to 3,513,198 shares at an issuance price of $14.23 per share and 1,375,600 shares of Series C Preferred for the settlement of the following (in thousands):
December 31,
20212020
Accrued compensation$1,274 $3,154 
Accrued direct research costs1,196 1,321 
Accrued operating expenses749 707 
Accrued interest— 1,483 
Total accrued expenses$3,219 $6,665 

Note 6—Convertible Notes PayablePayable.
AsFrom the period May through December 2022, Former Elicio issued 3,589,820 shares of December 31, 2020,Series C Preferred Shares for gross proceeds of approximately $41.8 million inclusive of the Company had convertible notes with an aggregate principalconversion of the outstanding amount of $39.8the Convertible Notes (as described in Note 12). Former Elicio incurred cash issuance costs of approximately $1.2 million and $1.8 million accrued interest outstanding.in connection with these shares.
Conversion of Convertible Notes PayablePreferred Stock
In January 2021,On June 1, 2023, Former Elicio completed the Merger with Angion in accordance with the Merger Agreement. Under the terms of the Merger Agreement, immediately prior to the effective time of the Merger, each share of Former Elicio’s preferred stock was converted into a share of Former Elicio’s common stock. At the closing of the Merger, the Company issued 33,978an aggregate of 5,375,751 shares of its common stock to Former Elicio stockholders, based on an exchange ratio of 0.0181 shares of the Company’s common stock for each share of Former Elicio’s common stock outstanding immediately prior to the Merger, including those shares of common stock issued upon the conversion of certainthe Former Elicio preferred stock. No shares and 3,589,820 shares of convertible preferred stock were issued during the years ended December 31, 2023 and 2022, respectively.
The authorized, issued and outstanding shares of the outstanding 2020 Notes. convertible preferred stock and liquidation preferences of Former Elicio as of December 31, 2022 were as follows (in thousands, except share and per share amounts):
Authorized SharesShares Issued and OutstandingAggregate Liquidation AmountProceeds Net of Liquidation Costs
Series A Convertible Preferred Shares132,387 132,387 $7,495$7,495
Series B Convertible Preferred Shares1,927,375 1,927,375 $72,803$62,944
Series C Convertible Preferred Shares4,888,798 2,938,158 $41,816$40,621
Total Preferred Shares6,948,560 4,997,920 

The Series A and Series B Preferred Shares were deemed changed as of October 18, 2022 into 132,387 and 1,927,375 preferred shares (retroactively restated for the reverse recapitalization as described in Note 3) due to the antidilutive protection triggered by the Series C Preferred Shares issued in October 2022 at a price below $1.00.
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

As a result of the Merger, the aggregate amount of 4,997,920 shares of Former Elicio preferred stock (retroactively restated for the reverse recapitalization as described in Note 3) were converted into 4,997,920 shares of Former Elicio's common stock to be exchanged for the same number of shares of the Company’s common stock.
At-The-Market Equity Program
In connectionMay 2022, the Company filed an automatically effective registration statement on Form S-3 (the “Registration Statement”) with the IPO in February 2021, withSEC that registers the offering, issuance, and sale of an IPOamount of common stock, preferred stock, debt securities, and warrants to purchase common stock, preferred stock and/or debt securities, not to exceed an aggregate initial offering price of $16.00$100 million. Simultaneously, the Company entered into an At-the-Market Equity Offering Sales Agreement with Stifel, Nicolaus & Company, Incorporated and Virtu Americas LLC, as sales agents, pursuant to which the Company may offer, issue or sell shares of its common stock having an aggregate offering price of up to $21 million from time to time in “at-the-market” offerings under the Registration Statement and related prospectus filed with the Registration Statement (the “ATM Program"). No sales were made under the ATM Program for the years ended December 31, 2023 and 2022.
Private Placement
In December 2023, the Company entered into a Subscription Agreement (the “Subscription Agreement”) with GKCC, LLC (the “Purchaser”), an entity controlled by a director of the Company, providing for the issuance and sale by the Company to the Purchaser of an aggregate of 1,213,000 shares of the Company’s common stock, par value $0.01 per share, at a purchase price per share of $5.81 (the “Offering”). See Note 16 - Related Party Transactions for a discussion of the remainingOffering.
Note 8—Stock-Based Compensation
2012 Plan and 2022 Plan
Pursuant to the Merger Agreement, the Company assumed the Former Elicio 2022 Equity Incentive Plan and the Former Elicio 2012 Equity Incentive Plan (the “Former Elicio Plans”) and all stock options issued and outstanding convertible notes were converted into 3,636,189under the Former Elicio Plans. Each outstanding and unexercised option to purchase Former Elicio common stock was adjusted with such Company stock options henceforth representing the right to purchase a number of shares of the Company’s common stock based on a conversion pricean exchange ratio of $11.57 per share. There were no convertible notes outstanding as0.0181. Any restriction on the exercise of December 31, 2021.

Note 7— Series C Convertible Preferred Stock
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The following table summarizesany Former Elicio stock options assumed by the aggregate values recorded forCompany continued in full force and effect and the Series C convertible preferredterm, exercisability, vesting schedule, accelerated vesting provisions, and any other provisions of such Former Elicio stock as of December 31, 2020 (in thousands):
At issuanceDecember 31, 2020
Series C convertible preferred stock recorded at amortized cost
Principal$22,308 $22,308 
Settlement premium5,577 5,577 
Unamortized discounts and fees(9,250)(1,884)
Net carrying amount$18,635 26,001 
Series C convertible preferred stock recorded at fair value
Series C convertible preferred stock issued in exchange for convertible notes2,254 
Change in fair value of Series C convertible preferred stock exchanged for convertible notes264 
Total Series C convertible preferred stock$28,519 

Conversion of Series C Convertible Preferred Stock
In connection withoption otherwise remained unchanged; provided, however, that the IPO in February 2021, with an initial public offering price of $16.00 per share, all shares of Series C convertible preferred stock outstanding plus accrued dividends were automatically converted into an aggregate of 2,234,640 shares of common stock with a conversion price of $11.57 per share. There were no shares of convertible preferred stock outstanding as of December 31, 2021.

Note 8—Stockholders' Equity
Common Stock
Each share of common stock entitles the holder to one vote on all matters submitted to a voteCompensation Committee of the Company’s stockholders. Common stockholders are not entitledboard of directors assumed the responsibility and the authority of Former Elicio’s board of directors or any committee thereof with respect to receive dividends, unless declaredeach Former Elicio stock option assumed by the Board of Directors.
Treasury stock
The retirement of treasury stock was recorded as a reduction of common stock and additional paid-in capital at the time such retirement was approved by our Board of Directors in October 2021.

As of December 31, 2021 and 2020, zero and $1.8 million was included in treasury stock in the consolidated balance sheets.

Note 9—Stock-Based CompensationCompany.
2015 Plan
In June 2019, the CompanyAngion approved an Amended and Restated 2015 Equity Incentive Plan (the "2015 Plan"“2015 Plan”) permitting the granting of incentive stock options, non-statutory stock options, restricted stock and other stock-based awards. Following the effectiveness of the 2021 Equity Incentive Award Plan ("(“2021 Plan"Plan”), the CompanyAngion ceased making grants under the 2015 Plan. However, the 2015 Plan continues to govern the terms and conditions of the outstanding awards granted under it. Shares of common stock subject to awards granted under the 2015 Plan that cease to be subject to such awards by forfeiture or otherwise after the termination of the 2015 Plan will be available for issuance under the 2021 Plan.
2021 Plan
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and Amendment to 2021 Plan
On January 25, 2021, the Company'sAngion’s board of directors approved the 2021 Plan which permits the granting of incentive stock options, non-statutory stock options, stock appreciation rights, restricted stock, restricted stock units and other stock-based awards to employees, directors, officers and consultants. The 2021 Plan provides that the number of shares reserved and available for issuance will automatically increase each January 1 by the lesser of 5% of the Company’s common stock outstanding on the immediately preceding December 31, or such lesser number of shares as determined by the Company’s board of directors. On January 25,March 17, 2023, Angion’s board of directors approved an amendment to the 2021 Plan to increase the cumulative number of shares of common stock equal to 11%reserved for issuance thereunder by 30,113 shares.
As of the post-IPO capitalization, with annual increases, up to a maximum of 60,000,000December 31, 2023, 540,171 shares of common stock were authorizedand 153,243 shares remain available for issuancefuture grants under the 2021 Plan.Plan and Former Elicio 2022 Equity Incentive Plan, respectively.
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

Stock Options
The fair value of each employee and non-employee stock option grant was estimated on the date of grant using the Black-Scholes option-pricing model based on the following inputs:
Year Ended December 31,
20212020
Risk-free interest rate0.7%0.7%
Expected dividend yield
Expected term in years6.05.9
Expected volatility71.8% - 73.1%70.8% - 86.8%
Each of these inputs is subjective and generally requires significant judgment.
Expected Term—The expected term represents the period that the Company’s stock-based awards are expected to be outstanding and is determined using the simplified method, which is based on the mid-point between the contractual term and vesting period.
Volatility—The Company determines volatility based on the historical volatilities of comparable publicly traded life science companies over a period equal to the expected term because it does not have sufficient trading history for its common stock price. The comparable companies were chosen based on the similar size, stage in the life cycle, or area of specialty. The Company will continue to apply this process until a sufficient amount of historical information regarding volatility on its own stock becomes available.
Risk-Free Interest Rate—The risk-free interest rate is determined by reference to the U.S. Treasury yield curve in effect at the time of grant of the award for time periods approximately equal to the expected term of the award.
Dividend Yield—The Company has never paid and has no plans to pay any dividends on its common stock. Therefore, the Company has used an expected dividend yield of 0.
Fair Value of Common Stock—For periods prior to the IPO, the Company determined the estimated fair value of its common stock using the Subject Company Transaction Method which includes the back-solve and scenario-based methods (Probability Weighted Expected Return Method) to arrive at estimated fair values. Subsequent to the IPO, the fair value was based on the closing price of the Company’s common stock on the grant date.
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The following assumptions were used to estimate the fair value of stock option awards: The following table summarizes information as of December 31, 2021 and activity during 2021 related to the Company’s stock option plans:options:
Number of
Shares
Weighted
Average
Exercise
Price
Weighted
Average
Remaining
Contractual
Life (in years)
Total
Intrinsic
Value
(in thousands)
Outstanding as of December 31, 20203,479,731 $6.97 8.4$15,140 
Options granted1,103,721 15.44 
Options forfeited(189,388)13.24 
Options exercised(152,939)6.40 
Options expired(10,963)7.67 
Outstanding as of December 31, 20214,230,162 $8.92 7.8$— 
Options vested and exercisable2,499,165 $7.11 7.1$— 
Number of
Stock Options
Weighted Average
Exercise Price
Weighted Average
Remaining Contractual Life
(in years)
Total
Intrinsic Value
(in thousands)
Outstanding as of December 31, 2022854,076 $5.24 7.72
Options granted219,672 9.68 
Existing Angion options outstanding351,656 61.99 
Options exercised(16,349)7.74 
Forfeited (unvested)(103,131)5.83 
Outstanding as of December 31, 20231,305,924 $21.27 7.43$2,510,341 
Options vested and exercisable871,564 $41.91 5.25$860,479 
The aggregate intrinsic value in the above table is calculated as the difference between the estimated fair value of the Company's common stock price and the exercise price of the stock options. 219,672 stock options were granted in the year ended December 31, 2023. The weighted average grant date fair value per share for the stock option grants during the yearsyear ended December 31, 2021 and 2020 were $10.25 and $5.48, respectively.2023 was $9.68. As of December 31, 2021,2023, the total unrecognized compensation related to unvested stock option awards granted was $6.1$2.4 million, which the Company expects to recognize over a weighted-average period of approximately 2.41.8 years years.
Restricted Stock and Restricted Stock Units
The Company's RSA and RSU activity for the years ended December 31, 2021 were as follows:
Shares of
Restricted Stock
Weighted
Average Grant
Date Fair Value
Per Share
Restricted
Stock Units
Weighted
Average Grant
Date Fair Value
Per Share
Outstanding at December 31, 202014,586 $6.05 74,144 $7.78 
Vested(14,586)6.05 (43,875)$8.16 
Forfeited00(12,764)$6.12 
Outstanding at December 31, 2021— 017,505 $9.51 
Vested as of December 31, 2021— 043,875 $8.16 
Performance-based Restricted Stock Units
The Company had 556,530 PSUs outstanding that were granted in June 2019. Vesting of the PSUs is dependent upon the satisfaction of both a service condition and a performance condition, an initial public offering or a change of control, as defined in the 2015 Plan. As the IPO occurred in February 2021, the performance condition was met and 185,510 PSUs vested and were released upon the closing of the IPO. Another 185,510 PSUs vested and released were in June 2021 upon the second anniversary of the grants. As of December 31, 2021, the Company had 185,510 PSUs outstanding.

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The following table summarizes the total stock-based compensation expense for the stock options, RSUs, RSAs, PSUs compensation issued in shares recorded in the consolidated statements of operations (in thousands):
Year Ended December 31,
20212020
For the Year Ended December 31,For the Year Ended December 31,
202320232022
Research and developmentResearch and development$5,898 $2,183 
General and administrativeGeneral and administrative6,143 2,533 
TotalTotal$12,041 $4,716 

The fair value of each option is estimated on the date of grant using Black-Scholes with the assumptions noted in the table below. The fair value of an award with only a service condition is amortized as compensation cost on a straight-line basis over the requisite service period of the awards, which is generally the vesting period. Compensation cost of awards that contain a performance condition are recognized when success is considered probable during the performance period. The Company has elected to account for forfeitures as they occur, rather than estimating the number of awards that are expected to vest. The risk-free interest rate is estimated using the weighted average rate of return on U.S. Treasury notes with a life that approximates the expected life of the option. The expected term of options granted to employees was calculated using the simplified method, which represents the average of the contractual term of the option and the weighted-average vesting period of the option. The Company uses the simplified method because it does not have sufficient historical option exercise data to provide a reasonable basis upon which to estimate expected term. The contractual life of the option was used for the expected life of options granted to non-employees. Expected volatility is based on the weighted average of the historical volatility of a peer group of publicly traded companies. The assumed dividend yield is based upon the Company's expectation of not paying dividends in the foreseeable future.
The fair value of each employee and non-employee stock option grant was estimated on the date of grant using Black-Scholes based on the following assumptions.

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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

OptionsDecember 31,
20232022
Risk-free interest rate3.68 - 4.49%1.64 - 3.88%
Expected dividend yield0.0%0.0%
Expected volatility71.70 - 75.50%60.30 - 73.20%
Expected term in years (employees)5.5 - 6.15.5 - 10
In March 2021 and June 2022, certain employees of the Company early exercised options to purchase shares of the Company’s common stock. The shares had not fully vested at the time of exercise and were recorded as an unvested option exercise liability. As the shares vest, the Company recognizes the shares and related expense as issuance of common stock upon settlement of restricted stock on the consolidated statements of convertible preferred stock and stockholders’ equity (deficit) for the years ended December 31, 2023 and 2022.
Employee Stock Purchase Plan
In January 2021, the board of directors of the CompanyAngion approved the Employee Stock Purchase Plan (the "ESPP"“ESPP”). The ESPP was effective on the date immediately prior to the effectiveness of the Company'sAngion's registration statement relating to the IPO. A total of 390,000 shares of common stock were initially reserved for issuance under the ESPP. The offering period and purchase period will bewas determined by the BoardAngion’s board of Directors.directors. No offering periods or purchasing periods were active as of December 31, 2023. As of December 31, 2021, 390,0002023, 68,958 shares under the ESPP remain available for purchase and no offerings hadhave been authorized.

Restricted Stock Units
Note 10—Warrants
In March 2021, Former Elicio granted restricted stock units (“RSUs”) with service and performance vesting conditions to an employee. The completion of the Merger satisfied the performance vesting criteria and triggered accelerated vesting for all unvested RSUs. As a result, the employee received 41,005 shares on June 1, 2023. To pay for the tax withholdings that were due upon vesting of the RSUs, the employee sold 14,455 shares to the Company, which are held in treasury stock as of December 31, 2023. As of December 31, 2021 and 2020, the outstanding warrants to purchase the Company's common stock were comprised of the following:2023, there are no RSUs outstanding.
ClassificationExercise
Price
Expiration
Date
Warrants at December 31,
20212020
Warrants issued with 2015 NotesLiability$6.43 7/5/28— 388,396 
Warrants issued with 2016 NotesLiability$6.43 7/5/28— 538,933 
Warrants issued with 2017 NotesLiability$6.43 7/5/28— 79,265 
Warrants issued with 2018 NotesLiability$6.43 7/5/28— 498,567 
Warrants issued with Conversion of Notes to Common StockEquity$8.03 8/31/28232,287 238,779 
Warrants issued with Units in the Equity OfferingEquity$8.03 8/31/28875,034 907,860 
Broker Warrants issued with Equity OfferingEquity$0.01 8/31/251,297 48,485 
Broker Warrants issued with 2019 NotesEquity$0.01 1/30/20— — 
Consultant WarrantsLiability$7.60 8/31/2839,505 39,506 
Total Warrants1,148,123 2,739,791 

Note 9—Warrants
In accordance with ASC 815, the warrants classified as liabilities are recorded at fair value at the issuance date, with changes in the fair value recognized in the consolidated statements of operations at the end of each reporting period. Refer to Note 4 for changes in the fair value recognized during the periods reported.
In accordance with ASC 815, the warrants classified as equity do not meet the definition of a derivative and are classified in stockholders' equity (deficit) in the consolidated balance sheets.
There was no warrant activity during the year ended December 31, 2023, other than the assumption of the previously issued Angion warrants by the Company.
The following table summarizes information regarding common stock warrants outstanding at December 31, 2023:
WarrantsWeighted
Average
Exercise
Price
Weighted Average Life (years)
Outstanding at December 31, 2022144,814 $53.59 6.5
Angion warrants assumed3,950 76.00 4.7
Outstanding at December 31, 2023148,764 $54.19 5.5

Note 10—Commitments and Contingencies
Legal Proceedings
From time to time, the Company may be involved in legal proceedings, as well as demands, claims and threatened litigation, which arise in the normal course of its business or otherwise.
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

The Company's warrant activityoutcome of any future litigation is uncertain. Such litigation, if not resolved, could result in substantial costs to the Company, including any costs associated with the indemnification of directors and officers.
The Company may be exposed to litigation in connection with its products under development and operations. The Company’s policy is to assess the likelihood of any adverse judgments or outcomes related to legal matters, as well as ranges of probable losses. The Company is not aware of any material legal matters.
License Agreements
In July 2012 and January 2016, Former Elicio licensed certain intellectual property from a university, of which the January 2016 agreement has been amended from time to time. The Company is required to pay certain contractual maintenance and milestone payments related to clinical trials and royalties on product sales over the term of the contract, with minimum annual royalty payments commencing in the calendar year after commercialization. In January 2019, Former Elicio licensed additional intellectual property and terminated a license obtained in July 2012 from the university. The license term for January 2016 license extends until terminated by either party under certain provisions. No commercialization royalties have been achieved.
Future minimum annual maintenance payments are $0.1 million for the year ended December 31, 2021 was as follows:
Warrants
Weighted
Average
Exercise
Price
Weighted
Average
Remaining
Contractual
Life (in years)
Balance—December 31, 20202,739,791 $7.00 4.9
Exercised (1)
(1,588,756)7.30 
Expired(2,912)8.03 
Balance—December 31, 20211,148,123 $8.01 1.2

(1) 613,892 shares from warrant exercised were tendered back to2023 and for each year thereafter. Future minimum annual payments are due until the Company to cover the exercise pricetermination of the warrant.
Conversion of Warrants
In February 2021, all warrants outstanding issued with 2015 Notes, 2016 Notes, 2017 Notes, and 2018 Notes with an exercise price of $6.43 per share were net exercised into an aggregate of 844,335 shares of common stock upon the IPO with a conversion price of $11.57 per share.

agreement.
Note 11—Commitments and ContingenciesLeases
Operating Leases
TheIn July 2021, the Company leasessigned an operating lease for office and laboratory space in Uniondale, New York from NovaPark, a related party, under an agreement classified as an operating lease that expires on June 20, 2026. Boston, Massachusetts (the “Boston Lease”).The Company's lease does not require any contingent rental payments, impose any financial restrictions, or contain any residual value guarantees. Variable expenses generally representBoston Lease commenced in February 2022 with the Company's share of the landlord's operating expenses, including management fees. The Company does not act as a lessor or have any leases classified as financing leases.
The Company leases office space in Fort Lee, New Jersey, comprising approximately 2,105 square feet for approximately $0.1 million per year, under a non-cancelable operating lease through March 31, 2022. However, this arrangement is excluded from the calculation of lease liabilities and right of use assets as its term is less than one year. The lease is subject to charges for common area maintenance and other costs. The Company is not going to renew the New Jersey lease after March 31, 2022.
In July 2020, the Company entered into a lease for office furniture in San Francisco, California set to expire in July 2025, with an annual lease paymentFebruary 2030. The Boston Lease has rent payments escalating annually, which total $11.1 million in the aggregate. As a result, at the commencement of approximately $13,000.
In February 2021,the Boston Lease, the Company entered intorecognized a right-of-use lease asset of $8.0 million with a corresponding lease liability of $8.0 million based on the present value of the minimum rental payments. In addition, the Company will make payments for operating expenses and real estate taxes. In June 2023, the Company secured a letter of credit for the deposit on the Boston Lease and has a deposit in the amount of $0.7 million, which was reported as Restricted Cash on the consolidated balance sheets as of December 31, 2023.
As part of the Merger Agreement, the Company also assumed a lease for clinical and regulatory space in Newton, Massachusetts (the “Newton lease”), comprising approximately 6,157 square feet for approximately $0.2 million per year, under a non-cancelable operating lease through June 30, 2024. Pursuant to
Lease expense for all leases for the Newton lease,years ended December 31, 2023 and 2022 was $1.5 million and $1.2 million, respectively. All expenses are included in operating expenses in the Company had 4 monthsaccompanying consolidated statements of free rent starting from February 15, 2021 to June 14, 2021. The Company has 1 option to extend the term of the lease for 3 years with 9 months’ notice.
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The following table provides the components of the Company's rent expense (in thousands):
For the Year Ended
December 31,
20212020
Operating leases
Operating lease cost$1,142 $1,099 
Variable cost473 646 
Operating lease expense1,615 1,745 
Short-term lease rent expense44 91 
Total rent expense$1,659 $1,836 
operations.
The following table summarizes quantitative information about the Company's NovaPark operating leases (dollars in thousands):
For the Year Ended
December 31,
20212020
For the year ended December 31,For the year ended December 31,
202320232022
Operating cash flows from operating leasesOperating cash flows from operating leases$1,179 $1,081 
Right-of-use assets exchanged for operating lease liabilitiesRight-of-use assets exchanged for operating lease liabilities$624 $88 
Weighted-average remaining lease term—operating leases (in years)Weighted-average remaining lease term—operating leases (in years)3.85.5Weighted-average remaining lease term—operating leases (in years)5.67.2
Weighted-average discount rate—operating leasesWeighted-average discount rate—operating leases10.1 %11.0 %Weighted-average discount rate—operating leases7.5 %8.0 %
As of December 31, 2021,2023, maturities of lease liabilities were as follows (in thousands):
Year Ended December 31,Amounts
2022$1,289 
20231,305 
20241,209 
20251,104 
2026516 
Thereafter— 
Total5,423 
Less present value discount(1,054)
Operating lease liabilities$4,369 
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

Financing obligation
Year Ended December 31,Amounts
2024$1,427 
20251,350 
20261,383 
20271,425 
20281,467 
Thereafter1,765 
Total8,817 
Less present value discount(1,900)
Operating lease liabilities6,917 
Less: operating lease liability, current portion910 
Operating lease liability, noncurrent portion$6,007 
Note 12—Convertible Notes Payable
In October and November 2021, the CompanyFormer Elicio entered into a saleconvertible promissory note agreements for an aggregate amount of $14.5 million (the “Convertible Notes”). The Convertible Notes accrue interest at 8% per annum and leaseback arrangement with a third-party financing institutionare payable upon demand at any time on or after October 4, 2022 (the “Demand date”). Interest expense for the year ended December 31, 2022 was $0.9 million.
There were $0.4 million of issuance costs incurred in 2021 and was initially recorded as a financing mechanismdiscount to fund certainthe carrying value of its capital expenditures primarilythe convertible note. Former Elicio recorded interest expense for the year ended December 31, 2022 related to operating equipment, whereby the physical asset is sold concurrentaccretion of the discount to the Convertible Notes due to issuance costs of $0.3 million.
The Convertible Notes included multiple conversion features. Former Elicio evaluated all the conversion features included within the Convertible Note agreements, noting that none of the features was considered to be predominant. Former Elicio also evaluated all conversion features under FASB ASC Topic 815, Derivatives and Hedging, and determined conversion features associated with an agreement to lease the asset back.qualified and non-qualified financings met the definition of a derivative and require bifurcation from the Convertible Notes. The initial leaseback term is 42 months starting from November 2021. The arrangement includes a renewal option as wellbifurcated embedded derivative of $2.9 million was recorded as a repurchase optionliability at fair value with a cap at the enddate of issuance based on the probability of occurrence of a triggering event taking place during the term of the term. The arrangement does not qualifyConvertible Notes and was recorded as an asset sale as controla discount to the carrying value of the equipment did not transferConvertible Note. Former Elicio recorded interest expense for the year ended December 31, 2022 related to the third party and is accounted for as a failed sale-leaseback. Therefore,accretion of the Company accounts fordiscount to the arrangement as a financing transaction and recordsConvertible Notes due to the proceeds received as a financing obligation. The leased assets are included in property and equipment, net on the consolidated balance sheets and are subject to depreciation.bifurcated embedded derivative of $2.3 million.
During the year ended December 31, 2021,2022, the Company received $0.3 millionincrease in connection with the sale and leaseback of certain equipment.
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The following table summarizes quantitative information about the Company's financing obligation (dollars in thousands):
For the Year Ended December 31,
2021
Cash flow information:
Proceeds from sale and leaseback arrangement$302 
Payments of financing obligation
Operating cash flows from financing obligation$
Financing cash flows from financing obligation$
Other information:
Weighted-average remaining lease term (in years)3.0 years
Weighted-average discount rate (in percent)1.1 %
Carrying value of leased asset included in Property and Equipment, net$270 
Depreciation associated with the leased asset$38 
As of December 31, 2021, maturities of financing obligation were as follows (in thousands):
Year Ended December 31,Amounts
2022$94 
202394 
202494 
202531 
2026— 
Thereafter— 
Total313 
Less present value discount(20)
Financing obligation$293 
Litigation
The Company is not a party to any material legal proceedings and is not aware of any pending or threatened claims. From time to time, the Company may be subject to various legal proceedings and claims that arise in the ordinary course of its business activities.
Indemnification
The Company enters into standard indemnification arrangements in the ordinary course of business. Pursuant to these arrangements, the Company indemnifies, holds harmless and agrees to reimburse the indemnified parties for losses suffered or incurred by the indemnified party, in connection with any trade secret, copyright, patent or other intellectual property infringement claim by any third party with respect to its technology. The term of these indemnification agreements is generally perpetual any time after the execution of the agreement. The maximum potential amount of future payments the Company could be required to make under these arrangements is not determinable. The Company has never incurred costs to defend lawsuits or settle claims related to these indemnification agreements. As a result, the Company believes the fair value of these agreements is minimal.
Paycheck Protection Program
In April 2020, the Company received fundsembedded derivative was determined to be $0.9 million and was recorded as interest expense in the amountaccompanying consolidated statements of $0.9operations.
On October 18, 2022, in conjunction with the Series C Preferred Shares issued on this same date, the Convertible Notes Payable totaling $14.5 million pursuantand the related accrued interest totaling $1.1 million automatically converted into 1,370,187 Series C Preferred Shares at an 80% discount to a loan under the Paycheck Protection ProgramSeries C Preferred Share issuance price per share of $14.23, or $11.39 per share. Just prior to settlement, the fair value of the 2020 CARES Act ("PPP") administered byembedded derivative was marked to market a final time to the Small Business Association. The loan hasaggregate value of $3.9 million. Former Elicio recorded an immaterial gain on extinguishment related to the difference in the total of Convertible Notes Payable, total accrued interest rate of 1.0% and a term of 24 months. No payments were due for the first 16 months, although interest accrued, and monthly payments were due over the next 8 months to retire the loan plus accrued interest. Funds
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from the loan could only be used for certain purposes, including payroll, benefits, rent and utilities, and a portionfinal fair value of the loan used to pay certain costs were forgivable, all as provided byembedded derivative versus the termsvalue of the PPP. The loan was evidenced by a promissory note, which contained customary events of default relating to, among other things, payment defaults and breaches of representations and warranties. The SBA approved the Company's PPP Loan forgiveness application on May 26, 2021 for the entire principal amount of the PPP Loan and accrued interest. As a result, the Company recorded a gainSeries C Preferred Shares issued based on the forgivenessoriginal issuance price of the loan in the amount of $0.9 million.
Employee Retention Credit ("ERC")
The Employee Retention Credit ("ERC") under the CARES Act is a refundable tax credit which encourages businesses to keep employees on the payroll during the COVID-19 pandemic. Eligible employers could qualify for up to $5,000 of credit for each employee based on qualified wages paid after March 12, 2020 and before January 1, 2021. The Internal Revenue Service ("IRS") subsequently issued Notice 2021-23 and Notice 2021-49 which collectively extended the ERC eligibility to cover qualified wages paid after December 31, 2020 and before January 1, 2022. Qualified wages are the wages paid to an employee for the time that the employee is not providing services due to an economic hardship, specifically, either (1) a full or partial suspension of operations by order of a governmental authority due to COVID-19, or (2) a significant decline in gross receipts.
During the years ended December 31, 2021 and 2020, the Company received $1.5 million and zero, respectively for ERC and applied the benefit as a reduction to the payroll expenses in the consolidated statement of operations.$14.23 per share.

Note 12—13—Income Taxes
The Company recognized no tax provision for the year ended December 31, 2021 and December 31, 2020. The difference between the Company's effective tax rate of 0% and the U.S. federal statutory tax rate of 21% is largely due to the Company's net operating losses, which are offset by the corresponding valuation allowance. Deferred income taxes reflect the net tax effects of temporary differences between the carrying amount of assets and liabilities for financial reporting purposes and the amounts used for income tax purposes. The Company has established a valuation allowance against net deferred tax assets due to the uncertainty that such assets will be realized. The Company periodically evaluates the recoverabilitycomponents of the deferred assets. At such time as it is determined that it is more likely than not that the deferred tax asset will be realized, the valuation allowance will be reduced.
Losses before income taxes includes the following components:
Year Ended December 31,
20212020
United States$(53,547)$(78,164)
Foreign(1,026)(1,943)
Total$(54,573)$(80,107)
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TheCompany’s provision for income taxes provision (benefit) for the years ended December 31, 20212023 and 20202022 consists of the following (in thousands):
December 31,
20212020
Current:
Federal$— $— 
United States— — 
Foreign— — 
          Total Current$— $— 
Deferred
Federal(5,460)(12,129)
State(4,779)(522)
Change in valuation allowance10,239 12,651 
          Total Deferred— — 
                   Total tax provision$— $— 
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

December 31,
20232022
Current:
Federal$— $— 
United States— — 
Foreign— — 
          Total Current— — 
Deferred
Federal7,743 5,162 
State3,116 2,102 
Foreign— — 
Change in valuation allowance(10,859)(7,264)
          Total Deferred— — 
                   Total tax provision$— $— 

The reconciliations between the federal statutory income tax rate and the Company's effective income tax rate were as follows:
Year Ended December 31,
20212020
Federal statutory income tax rate21.0 %21.0 %
State taxes, net of federal tax benefit0.6 %
Stock compensation(2.3)%(0.9)%
Foreign rate differential(0.1)%(0.5)%
Interest(4.3)%
R&D and other tax credit changes2.8 %(1.1)%
Permanent items(7.3)%(4.7)%
Nontaxable Income0.3 %
Other1.4 %
Change in valuation allowance(10.1)%(15.8)%
Effective income tax rate0.0 %0.0 %
Year Ended December 31,
20232022
Statutory federal income tax rate21.0 %21.0 %
State tax, net of federal benefits6.2 %5.1 %
Permanent differences(0.3)%(4.6)%
Federal research and development credits3.1 %2.6 %
State research and development credits0.8 %0.9 %
Other differences0.1 %0.9 %
Change in valuation allowance(30.9)%(25.9)%
Effective income tax rate0.0 %0.0 %
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SignificantThe principal components of the Company's net deferred tax asset at December 31, 20212023 and 20202022 were as follows (in thousands):
December 31,
20212020
Deferred tax assets
Net operating loss carryforwards$29,211 $22,686 
R&D and other tax credit carryovers6,752 4,718 
Lease liability1,224 956 
Stock-based compensation3,070 1,323 
Accrued compensation and other expenses536 658 
Fixed assets— 
Total deferred tax assets40,793 30,344 
Deferred tax liabilities
Fixed assets(37)— 
Right of use assets(1,046)(874)
Valuation allowance(39,710)(29,470)
Deferred tax assets, net of allowance$— $— 
December 31,
20232022
Deferred tax assets (liabilities):
Net operating loss carryforwards$60,696 $19,146 
Research and development tax credit carryovers12,940 3,820 
Capitalized research and development13,686 4,304 
Lease liability1,897 1,949 
Other2,732 611 
ROU Asset(1,800)(1,915)
Property and equipment(33)(37)
Total deferred tax assets90,118 27,878 
Less: Deferred tax asset valuation allowance(90,118)(27,878)
Net deferred tax asset$— $— 
As of
Net operating losses (“NOL”) generated before December 31, 2021, the Company has federal net operating loss carryforwards of approximately $118.5 million available to reduce future taxable income, if any, for federal income tax purposes. Approximately $9.6 million of federal net operating losses2017 can be carried forward to future20 years and carried back two years under the Internal Revenue Code (“IRC”). NOLs arising in tax years and begin to expire in 2035. The federal net operating losses generated for the years beginningended after December 31, 2017 approximately $108.9 million in total, can beare limited to 80% of taxable income, only carried forward and carried forward indefinitely. The Company
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

has no income tax expense due to operating losses incurred for the years ended December 31, 2023 and 2022. The NOL carryforward may be subject to an annual limitation under Section 382 and 383Company has provided a valuation allowance for the full amount of the Internal Revenue Codenet deferred tax assets as, based on all available evidence, it is considered more likely than not that all the recorded deferred tax assets will not be realized in a future period. The increase in the net deferred tax assets and valuation allowance is primarily due to the reverse merger transaction with Angion in June 2023 (as described in Note 3). For federal income tax purposes the transaction qualified as a tax-free reverse subsidiary merger pursuant to IRC Section 368 (a)(2)(E) and therefore the historical tax basis in the assets acquired and liabilities assumed was carried over upon acquisition. Net deferred tax assets acquired of 1986,$50.1 million with an offsetting valuation allowance of $50.1 million are primarily related to pre-merger net operating loss and similarresearch and development credits carryovers. At December 31, 2023, Elicio has federal NOLs of $237.8 million, of which $19.1 million was generated before the tax year ended December 31, 2017, and state provisions ifNOLs of $170.4 million. If not utilized, certain NOLs for federal and state tax purposes will start to expire beginning in 2032. At December 31, 2023, Elicio has $11.1 million and $2.2 million of federal and state research and development credit carryforwards, respectively, that start to expire in 2027.
As the Company experienced one or more ownershiphas not yet achieved profitable operations, management believes the tax benefits as of December 31, 2023 did not satisfy the realization criteria set forth in ASC Topic 740, Income Taxes and, therefore, has recorded a full valuation allowance for the entire deferred tax asset. The valuation allowance increased in 2023 by $62.2 million due to the increase in the deferred tax assets by the same amount, primarily due to NOL carryforwards. The Company’s effective income tax rate differed from the federal statutory rate primarily due to state taxes and the Company’s full valuation allowance, the latter of which reduced the Company’s effective federal income tax rate to zero.
Ownership changes, which wouldas defined in the IRC, may limit the amount of NOL and tax creditnet operating loss carryforwards that can be utilized annually to offset future taxable income and tax respectively. In general, an ownership change as defined bypursuant to IRC Section 382 and 383, results fromor similar provisions. Subsequent ownership changes could further affect the transactions increasing ownership of certain stockholders or public groupslimitation in the stock of the corporation of more than 50 percentage points over a three-year period.future years. The Company has not completed a Section 382 and 383 analysisstudy to assess whether an ownershipa change of control has occurred or whether there have been multiple ownership changes of control since the Company'sCompany’s formation due to the significant complexity and cost associated with such study and the factbecause there maycould be additional such ownership changes in control in the future. IfAs a result, the Company is not able to estimate the effect of the change in ownership werecontrol, if any, on the Company’s ability to have occurred or occursutilize net operating loss and research and development credit carryforwards in the future, the NOL and tax credits carryforwards could be eliminated or restricted. If eliminated, the related asset would be removed from the deferred tax asset schedule with a corresponding reduction in the valuation allowance. Due to the existence of the valuation allowance, limitations created by future ownership changes, if any, will not impact the Company's effective tax rate.

future.
The Company files income tax returns in the United States, Australia, California, Connecticut, Delaware, Florida, Iowa, Massachusetts, Missouri, New YorkHampshire, New Jersey, and New Jersey. DueTennessee. All tax years from 2020 to 2023 remain open to examination by the Company's losses incurred,major taxing jurisdictions to which the Company is subject, to the income taxas carryforward attributes generated in years past may still be adjusted upon examination by the Internal Revenue Service (“IRS”) or other authorities since inception.if they have or will be used in a future period. To its knowledge, the Company is not currently under examination by the IRS or any other jurisdictions for any tax years.
As of December 31, 2023, the Company had $4.1 million of uncertain tax positions related to prior research tax credits that may not be substantiated upon audit. The Company's policy isCompany does not anticipate that uncertain tax positions will decrease within the next 12 months. The Company has elected to recognize interest expense and penalties related to income tax matters as tax expense. Asa component of December 31, 2021 and 2020, there were no significant accruals for interest related to unrecognized tax benefits or tax penalties.

At December 31, 2021, the Company's reserve for unrecognized tax benefits is approximately $3.7 million. Due to the full valuation allowance at December 31, 2021, current adjustments to the unrecognized benefits will have no impact to the Company's effective income tax rate.
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Reconciliationexpense, of uncertain tax positions as of December 31, 2021 and 2020 was as follows (in thousands):
December 31,
20212020
Beginning Balance$2,579 $— 
Additions
Additions for current year1,073 633 
Additions for prior years23 1,946 
Ending Balance$3,675 $2,579 
Total amount of unrecognized tax benefits, if recognized, would affect the effective tax rate was as follows (in thousands):
December 31,
20212020
Unrecognized benefits that would affect the effective tax rate$— $— 
Unrecognized benefits that would not affect the effective tax rate3,675 2,579 
Total unrecognized benefits$3,675 $2,579 

The Company does not anticipate material changes to its uncertain tax positions for the next twelve months.

In conjunction with the 2018 Act that amends the Internal Revenue Code that reduced the U.S. corporate tax rate from 35% to 21% effective January 1, 2018 and modified policies, credits, and deductions (the "Tax Act"), the SEC staff issued Staff Accounting Bulletin No. 118 ("SAB 118") to address the application of GAAP in situations when a registrant does not have the necessary information available, prepared,which no interest or analyzed (including computations) in reasonable detail to complete the accounting for certain income tax effects of the Tax Act. The Company has completed its evaluation and determined that there was no net impact on the Company's consolidated financial statementspenalties were recorded for the years ended December 31, 20212023 and 2020 as the corresponding adjustment was made to the valuation allowance.

2022.
Note 13—14—Employee Benefit Plan
Employee Benefit PlanSeries C Convertible Preferred Stock
The Company sponsors a retirement savings plan that is intendedIn May 2022, Former Elicio authorized the sale and issuance of up to qualify760,200 shares of $0.06 par value Series C Preferred Shares at an original issuance price of $66.30 per share and up to 325,800 shares of Series C Preferred for favorable tax treatment under Section 401(a)the settlement of the Code,convertible notes payable. The Series C Preferred Shares financing was structured to be issued in rolling closes in 2022.
In October 2022, Elicio increased the authorized number of Series C Preferred Shares to 3,513,198 shares at an issuance price of $14.23 per share and contains a cash or deferred feature that is intended to meet1,375,600 shares of Series C Preferred for the requirements of Section 401(k)settlement of the Code. Participants may make pre-tax and certain after-tax (Roth) salary deferral contributionsConvertible Notes Payable.
From the period May through December 2022, Former Elicio issued 3,589,820 shares of Series C Preferred Shares for gross proceeds of approximately $41.8 million inclusive of the conversion of the outstanding amount of the Convertible Notes (as described in Note 12). Former Elicio incurred cash issuance costs of approximately $1.2 million in connection with these shares.
Conversion of Convertible Preferred Stock
On June 1, 2023, Former Elicio completed the Merger with Angion in accordance with the Merger Agreement. Under the terms of the Merger Agreement, immediately prior to the plan from their eligible earnings upeffective time of the Merger, each share of Former Elicio’s preferred stock was converted into a share of Former Elicio’s common stock. At the closing of the Merger, the Company issued an aggregate of 5,375,751 shares of its common stock to the statutorily prescribed annual limit under the Code. Participants who are 50 years of age or older may contribute additional amountsFormer Elicio stockholders, based on the statutory limits for catch-up contributions. Participant contributions are held in trust as required by law. No minimum benefit is provided under the plan. An employee’s interest in his or her salary deferral contributions is 100% vested when contributed. Contributions, subject to established limits, are matched at a dollar for dollar rate up to 3%an exchange ratio of an individual’s earnings and fifty cents on the dollar on the next 4-5% of earnings.
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Note 14—Net Loss Per Share
The following table sets forth the computation0.0181 shares of the Company’s basiccommon stock for each share of Former Elicio’s common stock outstanding immediately prior to the Merger, including those shares of common stock issued upon conversion of the Former Elicio preferred stock. No shares and diluted net loss per share attributable to common stockholders, which excludes3,589,820 shares which are legallyof convertible preferred stock were issued during the years ended December 31, 2023 and 2022, respectively.
The authorized, issued and outstanding but subject to repurchase byshares of the Company (inconvertible preferred stock and liquidation preferences of Former Elicio as of December 31, 2022 were as follows (in thousands, except share and per share data)amounts):
Year Ended December 31,
20212020
Numerator
Net loss attributable to common stockholders$(54,573)$(80,107)
Denominator:
Weighted-average shares used in computing net loss per share attributable to common stockholders, basic and diluted28,244,82514,762,120
Net loss per share attributable to common stockholders, basic and diluted$(1.93)$(5.43)
Authorized SharesShares Issued and OutstandingAggregate Liquidation AmountProceeds Net of Liquidation Costs
Series A Convertible Preferred Shares132,387 132,387 $7,495$7,495
Series B Convertible Preferred Shares1,927,375 1,927,375 $72,803$62,944
Series C Convertible Preferred Shares4,888,798 2,938,158 $41,816$40,621
Total Preferred Shares6,948,560 4,997,920 

The tableSeries A and Series B Preferred Shares were deemed changed as of October 18, 2022 into 132,387 and 1,927,375 preferred shares (retroactively restated for the reverse recapitalization as described in Note 3) due to the antidilutive protection triggered by the Series C Preferred Shares issued in October 2022 at a price below provides potentially dilutive securities not included in the calculation$1.00.
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

As a result of the diluted net loss per share becauseMerger, the aggregate amount of 4,997,920 shares of Former Elicio preferred stock (retroactively restated for the reverse recapitalization as described in Note 3) were converted into 4,997,920 shares of Former Elicio's common stock to do so would be anti-dilutive:
December 31,
20212020
Shares issuable upon exercise of stock options4,230,1623,479,731
Shares issuable upon the exercise of warrants1,148,1232,739,791
Shares issuable upon conversion of the convertible notes(1)
5,603,388
Shares issuable upon conversion of the Series C preferred stock(1)
3,920,172
Non-vested shares under restricted stock unit grants203,01558,951
Non-vested shares under restricted stock grants14,585
Total5,581,30015,816,618
___________________________________
(1)Theexchanged for the same number of shares issuable upon conversion of the 2019 Notes, 2020 NotesCompany’s common stock.
At-The-Market Equity Program
In May 2022, the Company filed an automatically effective registration statement on Form S-3 (the “Registration Statement”) with the SEC that registers the offering, issuance, and Series Csale of an amount of common stock, preferred stock, has been estimated using the Company'sdebt securities, and warrants to purchase common stock, fair value at December 31, 2020, discounted by 20%.

Note 15—Related Party Transactions
Ohr Investment
In a seriespreferred stock and/or debt securities, not to exceed an aggregate initial offering price of investments in November 2013 and July 2017,$100 million. Simultaneously, the Company invested a total of $150,000entered into an At-the-Market Equity Offering Sales Agreement with Stifel, Nicolaus & Company, Incorporated and Virtu Americas LLC, as sales agents, pursuant to acquire a membership interest in Ohr Cosmetics, LLC ("Ohr"), an affiliated company.
The Company owns and the family of the Company's director and Chairman Emeritus owns approximately 2.4% and 80.6%, respectively, of the membership interests in Ohr. Our Chief Executive Officer is also owns approximately 0.80% of the membership interests in Ohr. The Chairman Emeritus’s son is the manager of Ohr.
In November 2013,which the Company granted Ohrmay offer, issue or sell shares of its common stock having an exclusive worldwide license,aggregate offering price of up to $21 million from time to time in “at-the-market” offerings under the Registration Statement and related prospectus filed with the right to sublicense,Registration Statement (the “ATM Program"). No sales were made under the Company's patent rights covering one of the Company's CYP26 inhibitors, ANG-3522, for the use in treating conditions of the skin or hair. Sublicensees may not grant further sublicenses under the Company's patent rights other than to affiliates of such sublicensees and entities with which sublicensees are collaborating for the research, development, manufacture and commercialization of the products. Ohr will pay the Company a royalty at a rate in the low single digits on gross revenue of products incorporating ANG-3522, and milestone payments potentially totaling up to $9.0 million based on achievement of sales milestones. Royalties and milestone payments will be paid until the later of 15 years from the first commercial sale of a licensed product or the last to expire licensed patent rights. The royalty rate is subject to adjustments under certain circumstances. The Company believes that the Ohr License was made on terms no less favorable to the Company than those that the Company could obtain from unaffiliated third parties.
No revenue from this license agreement was recognized for the years presented.
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NovaPark Investment and Lease
As of December 31, 2021, the Company had a 10% interest in NovaPark. Members of the Company's director and Chairman Emeritus’s 's immediate family own a majority of the membership interests of NovaPark. The Company accounts for its aggregate 10% investment in NovaPark under the equity method. The following table provides the activity for the NovaPark investmentATM Program for the years ended December 31, 2023 and 2022.
Private Placement
In December 2023, the Company entered into a Subscription Agreement (the “Subscription Agreement”) with GKCC, LLC (the “Purchaser”), an entity controlled by a director of the Company, providing for the issuance and sale by the Company to the Purchaser of an aggregate of 1,213,000 shares of the Company’s common stock, par value $0.01 per share, at a purchase price per share of $5.81 (the “Offering”). See Note 16 - Related Party Transactions for a discussion of the Offering.
Note 8—Stock-Based Compensation
2012 Plan and 2022 Plan
Pursuant to the Merger Agreement, the Company assumed the Former Elicio 2022 Equity Incentive Plan and the Former Elicio 2012 Equity Incentive Plan (the “Former Elicio Plans”) and all stock options issued and outstanding under the Former Elicio Plans. Each outstanding and unexercised option to purchase Former Elicio common stock was adjusted with such Company stock options henceforth representing the right to purchase a number of shares of the Company’s common stock based on an exchange ratio of 0.0181. Any restriction on the exercise of any Former Elicio stock options assumed by the Company continued in full force and effect and the term, exercisability, vesting schedule, accelerated vesting provisions, and any other provisions of such Former Elicio stock option otherwise remained unchanged; provided, however, that the Compensation Committee of the Company’s board of directors assumed the responsibility and the authority of Former Elicio’s board of directors or any committee thereof with respect to each Former Elicio stock option assumed by the Company.
2015 Plan
In June 2019, Angion approved an Amended and Restated 2015 Equity Incentive Plan (the “2015 Plan”) permitting the granting of incentive stock options, non-statutory stock options, restricted stock and other stock-based awards. Following the effectiveness of the 2021 Incentive Award Plan (“2021 Plan”), Angion ceased making grants under the 2015 Plan. However, the 2015 Plan continues to govern the terms and 2020conditions of the outstanding awards granted under it. Shares of common stock subject to awards granted under the 2015 Plan that cease to be subject to such awards by forfeiture or otherwise after the termination of the 2015 Plan will be available for issuance under the 2021 Plan.
2021 Plan and Amendment to 2021 Plan
On January 25, 2021, Angion’s board of directors approved the 2021 Plan which permits the granting of incentive stock options, non-statutory stock options, stock appreciation rights, restricted stock, restricted stock units and other stock-based awards to employees, directors, officers and consultants. The 2021 Plan provides that the number of shares reserved and available for issuance will automatically increase each January 1 by the lesser of 5% of the Company’s common stock outstanding on the immediately preceding December 31, or such lesser number of shares as determined by the Company’s board of directors. On March 17, 2023, Angion’s board of directors approved an amendment to the 2021 Plan to increase the cumulative number of shares of common stock reserved for issuance thereunder by 30,113 shares.
As of December 31, 2023, 540,171 shares and 153,243 shares remain available for future grants under the 2021 Plan and Former Elicio 2022 Equity Incentive Plan, respectively.
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Notes to Consolidated Financial Statements (Continued)

Stock Options
The following table summarizes information and activity related to the Company’s stock options:
Number of
Stock Options
Weighted Average
Exercise Price
Weighted Average
Remaining Contractual Life
(in years)
Total
Intrinsic Value
(in thousands)
Outstanding as of December 31, 2022854,076 $5.24 7.72
Options granted219,672 9.68 
Existing Angion options outstanding351,656 61.99 
Options exercised(16,349)7.74 
Forfeited (unvested)(103,131)5.83 
Outstanding as of December 31, 20231,305,924 $21.27 7.43$2,510,341 
Options vested and exercisable871,564 $41.91 5.25$860,479 
The aggregate intrinsic value in the above table is calculated as the difference between the estimated fair value of the Company's common stock price and the exercise price of the stock options. 219,672 stock options were granted in the year ended December 31, 2023. The weighted average grant date fair value per share for the stock option grants during the year ended December 31, 2023 was $9.68. As of December 31, 2023, the total unrecognized compensation related to unvested stock option awards granted was $2.4 million, which the Company expects to recognize over a weighted-average period of approximately 1.8 years years.
The following table summarizes total stock-based compensation expense recorded in the consolidated statements of operations (in thousands):
Year Ended December 31,
20212020
Beginning balance$672 $849 
Losses of equity method investment(96)(71)
Distribution from NovaPark(3)(106)
Ending balance$573 $672 
For the Year Ended December 31,
20232022
Research and development$552 $291 
General and administrative627 288 
Total$1,179 $579 

The Company rents office and laboratory spacefair value of each option is estimated on the date of grant using Black-Scholes with the assumptions noted in Uniondale, New York from NovaPark underthe table below. The fair value of an award with only a leaseservice condition is amortized as compensation cost on a straight-line basis over the requisite service period of the awards, which is generally the vesting period. Compensation cost of awards that expires June 20, 2026.contain a performance condition are recognized when success is considered probable during the performance period. The Company has elected to account for forfeitures as they occur, rather than estimating the number of awards that are expected to vest. The risk-free interest rate is estimated using the weighted average rate of return on U.S. Treasury notes with a life that approximates the expected life of the option. The expected term of options granted to employees was calculated using the simplified method, which represents the average of the contractual term of the option and the weighted-average vesting period of the option. The Company uses the simplified method because it does not have sufficient historical option exercise data to provide a reasonable basis upon which to estimate expected term. The contractual life of the option was used for the expected life of options granted to non-employees. Expected volatility is based on the weighted average of the historical volatility of a peer group of publicly traded companies. The assumed dividend yield is based upon the Company's expectation of not paying dividends in the foreseeable future.
The fair value of each employee and non-employee stock option grant was estimated on the date of grant using Black-Scholes based on the following assumptions.

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Notes to Consolidated Financial Statements (Continued)

OptionsDecember 31,
20232022
Risk-free interest rate3.68 - 4.49%1.64 - 3.88%
Expected dividend yield0.0%0.0%
Expected volatility71.70 - 75.50%60.30 - 73.20%
Expected term in years (employees)5.5 - 6.15.5 - 10
In March 2021 and June 2022, certain employees of the Company early exercised options to purchase shares of the Company’s common stock. The shares had not fully vested at the time of exercise and were recorded rentas an unvested option exercise liability. As the shares vest, the Company recognizes the shares and related expense for fixed lease paymentsas issuance of $1.1 millioncommon stock upon settlement of restricted stock on the consolidated statements of convertible preferred stock and $1.0 millionstockholders’ equity (deficit) for the years ended December 31, 2023 and 2022.
Employee Stock Purchase Plan
In January 2021, the board of directors of Angion approved the Employee Stock Purchase Plan (the “ESPP”). The ESPP was effective on the date immediately prior to the effectiveness of the Angion's registration statement relating to the IPO. The offering period and 2020, respectively. purchase period was determined by Angion’s board of directors. No offering periods or purchasing periods were active as of December 31, 2023. As of December 31, 2023, 68,958 shares under the ESPP remain available for purchase and no offerings have been authorized.
Restricted Stock Units
In March 2021, Former Elicio granted restricted stock units (“RSUs”) with service and performance vesting conditions to an employee. The completion of the Merger satisfied the performance vesting criteria and triggered accelerated vesting for all unvested RSUs. As a result, the employee received 41,005 shares on June 1, 2023. To pay for the tax withholdings that were due upon vesting of the RSUs, the employee sold 14,455 shares to the Company, which are held in treasury stock as of December 31, 2023. As of December 31, 2023, there are no RSUs outstanding.
Note 9—Warrants
In accordance with ASC 815, the warrants classified as liabilities are recorded at fair value at the issuance date, with changes in the fair value recognized in the consolidated statements of operations at the end of each reporting period. Refer to Note 4 for changes in the fair value recognized during the periods reported.
In accordance with ASC 815, the warrants classified as equity do not meet the definition of a derivative and are classified in stockholders' equity in the consolidated balance sheets.
There was no warrant activity during the year ended December 31, 2023, other than the assumption of the previously issued Angion warrants by the Company.
The following table summarizes information regarding common stock warrants outstanding at December 31, 2023:
WarrantsWeighted
Average
Exercise
Price
Weighted Average Life (years)
Outstanding at December 31, 2022144,814 $53.59 6.5
Angion warrants assumed3,950 76.00 4.7
Outstanding at December 31, 2023148,764 $54.19 5.5

Note 10—Commitments and Contingencies
Legal Proceedings
From time to time, the Company may be involved in legal proceedings, as well as demands, claims and threatened litigation, which arise in the normal course of its business or otherwise.
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The outcome of any future litigation is uncertain. Such litigation, if not resolved, could result in substantial costs to the Company, including any costs associated with the indemnification of directors and officers.
The Company recordedmay be exposed to litigation in connection with its products under development and operations. The Company’s policy is to assess the likelihood of any adverse judgments or outcomes related to legal matters, as well as ranges of probable losses. The Company is not aware of any material legal matters.
License Agreements
In July 2012 and January 2016, Former Elicio licensed certain intellectual property from a university, of which the January 2016 agreement has been amended from time to time. The Company is required to pay certain contractual maintenance and milestone payments related to clinical trials and royalties on product sales over the term of the contract, with minimum annual royalty payments commencing in the calendar year after commercialization. In January 2019, Former Elicio licensed additional intellectual property and terminated a license obtained in July 2012 from the university. The license term for January 2016 license extends until terminated by either party under certain provisions. No commercialization royalties have been achieved.
Future minimum annual maintenance payments are $0.1 million for the year ended December 31, 2023 and for each year thereafter. Future minimum annual payments are due until the termination of the agreement.
Note 11—Leases
Operating Leases
In July 2021, the Company signed an operating lease for office and laboratory space in Boston, Massachusetts (the “Boston Lease”).The Boston Lease commenced in February 2022 with the term set to expire in February 2030. The Boston Lease has rent payments escalating annually, which total $11.1 million in the aggregate. As a result, at the commencement of the Boston Lease, the Company recognized a right-of-use lease asset of $8.0 million with a corresponding lease liability of $8.0 million based on the present value of the minimum rental payments. In addition, the Company will make payments for operating expenses and real estate taxes. In June 2023, the Company secured a letter of credit for the deposit on the Boston Lease and has a deposit in the amount of $0.7 million, which was reported as Restricted Cash on the consolidated balance sheets as of December 31, 2023.
As part of the Merger Agreement, the Company also assumed a lease for clinical and regulatory space in Newton, Massachusetts (the “Newton lease”), comprising approximately 6,157 square feet for approximately $0.2 million per year, under a non-cancelable operating lease through June 30, 2024.
Lease expense for variable expenses related to the lease of $0.5 million and $0.6 millionall leases for the years ended December 31, 20212023 and 2020,2022 was $1.5 million and $1.2 million, respectively. See Note 11.All expenses are included in operating expenses in the accompanying consolidated statements of operations.
Convertible NotesThe following table summarizes quantitative information about the Company's operating leases (dollars in thousands):
In connection with the IPO in February 2021, Victor Ganzi, Gilbert Omenn and Karen Wilson, directors of the Company, and Raj Venkatesan, brother of the Chief Executive Officer and director of the Company, converted all their outstanding convertible notes into an aggregate of 149,500 shares of common stock with a conversion price of $11.57.
For the year ended December 31,
20232022
Operating cash flows from operating leases$1,380 $1,106 
Right-of-use assets exchanged for operating lease liabilities$— $8,017 
Weighted-average remaining lease term—operating leases (in years)5.67.2
Weighted-average discount rate—operating leases7.5 %8.0 %
As of December 31, 2023, maturities of lease liabilities were as follows (in thousands):
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Notes to Consolidated Financial Statements (Continued)

Year Ended December 31,Amounts
2024$1,427 
20251,350 
20261,383 
20271,425 
20281,467 
Thereafter1,765 
Total8,817 
Less present value discount(1,900)
Operating lease liabilities6,917 
Less: operating lease liability, current portion910 
Operating lease liability, noncurrent portion$6,007 
Note 12—Convertible Notes Payable
In October and November 2021, Former Elicio entered into convertible promissory note agreements for an aggregate amount of $14.5 million (the “Convertible Notes”). The Convertible Notes accrue interest at 8% per annum and are payable upon demand at any time on or after October 4, 2022 (the “Demand date”). Interest expense for the year ended December 31, 2022 was $0.9 million.
There were $0.4 million of issuance costs incurred in 2021 and was initially recorded as a discount to the carrying value of the convertible note. Former Elicio recorded interest expense for the year ended December 31, 2022 related to the accretion of the discount to the Convertible Notes due to issuance costs of $0.3 million.
The Convertible Notes included multiple conversion features. Former Elicio evaluated all the conversion features included within the Convertible Note agreements, noting that none of the features was considered to be predominant. Former Elicio also evaluated all conversion features under FASB ASC Topic 815, Derivatives and Hedging, and determined conversion features associated with the qualified and non-qualified financings met the definition of a derivative and require bifurcation from the Convertible Notes. The bifurcated embedded derivative of $2.9 million was recorded as a liability at fair value at the date of issuance based on the probability of occurrence of a triggering event taking place during the term of the Convertible Notes and was recorded as a discount to the carrying value of the Convertible Note. Former Elicio recorded interest expense for the year ended December 31, 2022 related to the accretion of the discount to the Convertible Notes due to the bifurcated embedded derivative of $2.3 million.
During the year ended December 31, 2022, the increase in the fair value of the embedded derivative was determined to be $0.9 million and was recorded as interest expense in the accompanying consolidated statements of operations.
On October 18, 2022, in conjunction with the Series C Preferred Shares issued on this same date, the Convertible Notes Payable totaling $14.5 million and the related accrued interest totaling $1.1 million automatically converted into 1,370,187 Series C Preferred Shares at an 80% discount to the Series C Preferred Share issuance price per share of $14.23, or $11.39 per share. Just prior to settlement, the fair value of the embedded derivative was marked to market a final time to the aggregate value of $3.9 million. Former Elicio recorded an immaterial gain on extinguishment related to the difference in the total of Convertible Notes Payable, total accrued interest and the final fair value of the embedded derivative versus the value of the Series C Preferred Shares issued based on the original issuance price of $14.23 per share.

Note 13—Income Taxes
The components of the Company’s provision for income taxes for the years ended December 31, 2023 and 2022 consists of the following (in thousands):
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Notes to Consolidated Financial Statements (Continued)

December 31,
20232022
Current:
Federal$— $— 
United States— — 
Foreign— — 
          Total Current— — 
Deferred
Federal7,743 5,162 
State3,116 2,102 
Foreign— — 
Change in valuation allowance(10,859)(7,264)
          Total Deferred— — 
                   Total tax provision$— $— 

The reconciliations between the federal statutory income tax rate and the Company's effective income tax rate were as follows:
Year Ended December 31,
20232022
Statutory federal income tax rate21.0 %21.0 %
State tax, net of federal benefits6.2 %5.1 %
Permanent differences(0.3)%(4.6)%
Federal research and development credits3.1 %2.6 %
State research and development credits0.8 %0.9 %
Other differences0.1 %0.9 %
Change in valuation allowance(30.9)%(25.9)%
Effective income tax rate0.0 %0.0 %
The principal components of the Company's net deferred tax asset at December 31, 2023 and 2022 were as follows (in thousands):
December 31,
20232022
Deferred tax assets (liabilities):
Net operating loss carryforwards$60,696 $19,146 
Research and development tax credit carryovers12,940 3,820 
Capitalized research and development13,686 4,304 
Lease liability1,897 1,949 
Other2,732 611 
ROU Asset(1,800)(1,915)
Property and equipment(33)(37)
Total deferred tax assets90,118 27,878 
Less: Deferred tax asset valuation allowance(90,118)(27,878)
Net deferred tax asset$— $— 

Net operating losses (“NOL”) generated before December 31, 2017 can be carried forward 20 years and carried back two years under the Internal Revenue Code (“IRC”). NOLs arising in tax years ended after December 31, 2017 are limited to 80% of taxable income, only carried forward and carried forward indefinitely. The Company
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Notes to Consolidated Financial Statements (Continued)

has no income tax expense due to operating losses incurred for the years ended December 31, 2023 and 2022. The Company has provided a valuation allowance for the full amount of the net deferred tax assets as, based on all available evidence, it is considered more likely than not that all the recorded deferred tax assets will not be realized in a future period. The increase in the net deferred tax assets and valuation allowance is primarily due to the reverse merger transaction with Angion in June 2023 (as described in Note 3). For federal income tax purposes the transaction qualified as a tax-free reverse subsidiary merger pursuant to IRC Section 368 (a)(2)(E) and therefore the historical tax basis in the assets acquired and liabilities assumed was carried over upon acquisition. Net deferred tax assets acquired of $50.1 million with an offsetting valuation allowance of $50.1 million are primarily related to pre-merger net operating loss and research and development credits carryovers. At December 31, 2023, Elicio has federal NOLs of $237.8 million, of which $19.1 million was generated before the tax year ended December 31, 2017, and state NOLs of $170.4 million. If not utilized, certain NOLs for federal and state tax purposes will start to expire beginning in 2032. At December 31, 2023, Elicio has $11.1 million and $2.2 million of federal and state research and development credit carryforwards, respectively, that start to expire in 2027.
As the Company has not yet achieved profitable operations, management believes the tax benefits as of December 31, 2023 did not satisfy the realization criteria set forth in ASC Topic 740, Income Taxes and, therefore, has recorded a full valuation allowance for the entire deferred tax asset. The valuation allowance increased in 2023 by $62.2 million due to the increase in the deferred tax assets by the same amount, primarily due to NOL carryforwards. The Company’s effective income tax rate differed from the federal statutory rate primarily due to state taxes and the Company’s full valuation allowance, the latter of which reduced the Company’s effective federal income tax rate to zero.
Ownership changes, as defined in the IRC, may limit the amount of net operating loss carryforwards that can be utilized annually to offset future taxable income pursuant to IRC Section 382 or similar provisions. Subsequent ownership changes could further affect the limitation in future years. The Company has not completed a study to assess whether a change of control has occurred or whether there have been multiple changes of control since the Company’s formation due to the significant complexity and cost associated with such study and because there could be additional changes in control in the future. As a result, the Company is not able to estimate the effect of the change in control, if any, on the Company’s ability to utilize net operating loss and research and development credit carryforwards in the future.
The Company files tax returns in the United States, Australia, California, Connecticut, Delaware, Florida, Iowa, Massachusetts, Missouri, New Hampshire, New Jersey, and Tennessee. All tax years from 2020 to 2023 remain open to examination by the major taxing jurisdictions to which the Company is subject, as carryforward attributes generated in years past may still be adjusted upon examination by the Internal Revenue Service (“IRS”) or other authorities if they have or will be used in a future period. To its knowledge, the Company is not currently under examination by the IRS or any other jurisdictions for any tax years.
As of December 31, 2023, the Company had $4.1 million of uncertain tax positions related to prior research tax credits that may not be substantiated upon audit. The Company does not anticipate that uncertain tax positions will decrease within the next 12 months. The Company has elected to recognize interest and penalties related to income tax matters as a component of income tax expense, of which no interest or penalties were no convertible notes outstanding.recorded for the years ended December 31, 2023 and 2022.
Note 14—Employee Benefit Plan
Series C Convertible Preferred Stock
In May 2022, Former Elicio authorized the sale and issuance of up to 760,200 shares of $0.06 par value Series C Preferred Shares at an original issuance price of $66.30 per share and up to 325,800 shares of Series C Preferred for the settlement of the convertible notes payable. The Series C Preferred Shares financing was structured to be issued in rolling closes in 2022.
In October 2022, Elicio increased the authorized number of Series C Preferred Shares to 3,513,198 shares at an issuance price of $14.23 per share and 1,375,600 shares of Series C Preferred for the settlement of the Convertible Notes Payable.
From the period May through December 2022, Former Elicio issued 3,589,820 shares of Series C Preferred Shares for gross proceeds of approximately $41.8 million inclusive of the conversion of the outstanding amount of the Convertible Notes (as described in Note 12). Former Elicio incurred cash issuance costs of approximately $1.2 million in connection with these shares.
Conversion of Convertible Preferred Stock
On June 1, 2023, Former Elicio completed the IPOMerger with Angion in February 2021, Jay Venkatesan, M.D.,accordance with the President and Chief Executive Officer and directorMerger Agreement. Under the terms of the Company converted all his outstandingMerger Agreement, immediately prior to the effective time of the Merger, each share of Former Elicio’s preferred stock was converted into a share of Former Elicio’s common stock. At the closing of the Merger, the Company issued an aggregate of 165,0945,375,751 shares of its common stock to Former Elicio stockholders, based on an exchange ratio of 0.0181 shares of the Company’s common stock for each share of Former Elicio’s common stock outstanding immediately prior to the Merger, including those shares of common stock with aissued upon conversion price of $11.57 per share. As of December 31, 2021, there were nothe Former Elicio preferred stock. No shares and 3,589,820 shares of convertible preferred stock outstanding.
Consultant Fees
Angion paid consulting fees under an agreement with the wife of the director and Chairman Emeritus of the Company for Company management services. Consultant fees paid to the wife were approximately 0 and $0.1 million inissued during the years ended December 31, 20212023 and 2020,2022, respectively. This consultant agreement was terminated in February 2022.
Other
Dr. Michael Yamin, a former memberThe authorized, issued and outstanding shares of the Boardconvertible preferred stock and liquidation preferences of DirectorsFormer Elicio as of December 31, 2022 were as follows (in thousands, except share and per share amounts):
Authorized SharesShares Issued and OutstandingAggregate Liquidation AmountProceeds Net of Liquidation Costs
Series A Convertible Preferred Shares132,387 132,387 $7,495$7,495
Series B Convertible Preferred Shares1,927,375 1,927,375 $72,803$62,944
Series C Convertible Preferred Shares4,888,798 2,938,158 $41,816$40,621
Total Preferred Shares6,948,560 4,997,920 

The Series A and Series B Preferred Shares were deemed changed as of October 18, 2022 into 132,387 and 1,927,375 preferred shares (retroactively restated for the reverse recapitalization as described in Note 3) due to the antidilutive protection triggered by the Series C Preferred Shares issued in October 2022 at a price below $1.00.
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Notes to Consolidated Financial Statements (Continued)

As a result of the Merger, the aggregate amount of 4,997,920 shares of Former Elicio preferred stock (retroactively restated for the reverse recapitalization as described in Note 3) were converted into 4,997,920 shares of Former Elicio's common stock to be exchanged for the same number of shares of the Company’s common stock.
At-The-Market Equity Program
In May 2022, the Company is a Scientific Advisorfiled an automatically effective registration statement on Form S-3 (the “Registration Statement”) with the SEC that registers the offering, issuance, and sale of an amount of common stock, preferred stock, debt securities, and warrants to purchase common stock, preferred stock and/or debt securities, not to exceed an aggregate initial offering price of $100 million. Simultaneously, the Company entered into an At-the-Market Equity Offering Sales Agreement with Stifel, Nicolaus & Company, Incorporated and Virtu Americas LLC, as sales agents, pursuant to which the Company may offer, issue or sell shares of its common stock having an aggregate offering price of up to $21 million from time to time in “at-the-market” offerings under the Registration Statement and related prospectus filed with the Registration Statement (the “ATM Program"). No sales were made under the ATM Program for Pearl Cohen Zedek Latzer Baratz LLP (Pearl Cohen). In the years ended December 31, 20212023 and 2020, the Company paid Pearl Cohen $3.9 thousand and $0.1 million in legal fees, respectively.2022.
Private Placement
In January 2018,December 2023, the Company also entered into a consulting agreementSubscription Agreement (the “Subscription Agreement”) with Dr. Yamin pursuant to which he agreed to provide consulting servicesGKCC, LLC (the “Purchaser”), an entity controlled by a director of the Company, providing for the issuance and sale by the Company to the Company inPurchaser of an aggregate of 1,213,000 shares of the areasCompany’s common stock, par value $0.01 per share, at a purchase price per share of biomedical research$5.81 (the “Offering”). See Note 16 - Related Party Transactions for a discussion of the Offering.
Note 8—Stock-Based Compensation
2012 Plan and development. 2022 Plan
Pursuant to the termsMerger Agreement, the Company assumed the Former Elicio 2022 Equity Incentive Plan and the Former Elicio 2012 Equity Incentive Plan (the “Former Elicio Plans”) and all stock options issued and outstanding under the Former Elicio Plans. Each outstanding and unexercised option to purchase Former Elicio common stock was adjusted with such Company stock options henceforth representing the right to purchase a number of shares of the consulting agreement, Dr. Yamin,Company’s common stock based on an exchange ratio of 0.0181. Any restriction on the exercise of any Former Elicio stock options assumed by the Company continued in his capacityfull force and effect and the term, exercisability, vesting schedule, accelerated vesting provisions, and any other provisions of such Former Elicio stock option otherwise remained unchanged; provided, however, that the Compensation Committee of the Company’s board of directors assumed the responsibility and the authority of Former Elicio’s board of directors or any committee thereof with respect to each Former Elicio stock option assumed by the Company.
2015 Plan
In June 2019, Angion approved an Amended and Restated 2015 Equity Incentive Plan (the “2015 Plan”) permitting the granting of incentive stock options, non-statutory stock options, restricted stock and other stock-based awards. Following the effectiveness of the 2021 Incentive Award Plan (“2021 Plan”), Angion ceased making grants under the 2015 Plan. However, the 2015 Plan continues to govern the terms and conditions of the outstanding awards granted under it. Shares of common stock subject to awards granted under the 2015 Plan that cease to be subject to such awards by forfeiture or otherwise after the termination of the 2015 Plan will be available for issuance under the 2021 Plan.
2021 Plan and Amendment to 2021 Plan
On January 25, 2021, Angion’s board of directors approved the 2021 Plan which permits the granting of incentive stock options, non-statutory stock options, stock appreciation rights, restricted stock, restricted stock units and other stock-based awards to employees, directors, officers and consultants. The 2021 Plan provides that the number of shares reserved and available for issuance will automatically increase each January 1 by the lesser of 5% of the Company’s common stock outstanding on the immediately preceding December 31, or such lesser number of shares as determined by the Company’s board of directors. On March 17, 2023, Angion’s board of directors approved an amendment to the 2021 Plan to increase the cumulative number of shares of common stock reserved for issuance thereunder by 30,113 shares.
As of December 31, 2023, 540,171 shares and 153,243 shares remain available for future grants under the 2021 Plan and Former Elicio 2022 Equity Incentive Plan, respectively.
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Notes to Consolidated Financial Statements (Continued)

Stock Options
The following table summarizes information and activity related to the Company’s stock options:
Number of
Stock Options
Weighted Average
Exercise Price
Weighted Average
Remaining Contractual Life
(in years)
Total
Intrinsic Value
(in thousands)
Outstanding as of December 31, 2022854,076 $5.24 7.72
Options granted219,672 9.68 
Existing Angion options outstanding351,656 61.99 
Options exercised(16,349)7.74 
Forfeited (unvested)(103,131)5.83 
Outstanding as of December 31, 20231,305,924 $21.27 7.43$2,510,341 
Options vested and exercisable871,564 $41.91 5.25$860,479 
The aggregate intrinsic value in the above table is calculated as the difference between the estimated fair value of the Company's common stock price and the exercise price of the stock options. 219,672 stock options were granted in the year ended December 31, 2023. The weighted average grant date fair value per share for the stock option grants during the year ended December 31, 2023 was $9.68. As of December 31, 2023, the total unrecognized compensation related to unvested stock option awards granted was $2.4 million, which the Company expects to recognize over a consultant, received $0.1 millionweighted-average period of approximately 1.8 years years.
The following table summarizes total stock-based compensation expense recorded in the consolidated statements of operations (in thousands):
For the Year Ended December 31,
20232022
Research and development$552 $291 
General and administrative627 288 
Total$1,179 $579 

The fair value of each option is estimated on the date of grant using Black-Scholes with the assumptions noted in the table below. The fair value of an award with only a service condition is amortized as compensation cost on a straight-line basis over the requisite service period of the awards, which is generally the vesting period. Compensation cost of awards that contain a performance condition are recognized when success is considered probable during the performance period. The Company has elected to account for forfeitures as they occur, rather than estimating the number of awards that are expected to vest. The risk-free interest rate is estimated using the weighted average rate of return on U.S. Treasury notes with a life that approximates the expected life of the option. The expected term of options granted to employees was calculated using the simplified method, which represents the average of the contractual term of the option and the weighted-average vesting period of the option. The Company uses the simplified method because it does not have sufficient historical option exercise data to provide a reasonable basis upon which to estimate expected term. The contractual life of the option was used for the expected life of options granted to non-employees. Expected volatility is based on the weighted average of the historical volatility of a peer group of publicly traded companies. The assumed dividend yield is based upon the Company's expectation of not paying dividends in the foreseeable future.
The fair value of each employee and non-employee stock option grant was estimated on the date of grant using Black-Scholes based on the following assumptions.

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Notes to Consolidated Financial Statements (Continued)

OptionsDecember 31,
20232022
Risk-free interest rate3.68 - 4.49%1.64 - 3.88%
Expected dividend yield0.0%0.0%
Expected volatility71.70 - 75.50%60.30 - 73.20%
Expected term in years (employees)5.5 - 6.15.5 - 10
In March 2021 and June 2022, certain employees of the Company early exercised options to purchase shares of the Company’s common stock. The shares had not fully vested at the time of exercise and were recorded as an unvested option exercise liability. As the shares vest, the Company recognizes the shares and related expense as issuance of common stock upon settlement of restricted stock on the consolidated statements of convertible preferred stock and stockholders’ equity (deficit) for the years ended December 31, 2023 and 2022.
Employee Stock Purchase Plan
In January 2021, the board of directors of Angion approved the Employee Stock Purchase Plan (the “ESPP”). The ESPP was effective on the date immediately prior to the effectiveness of the Angion's registration statement relating to the IPO. The offering period and 2020. Dr. Yamin resigned frompurchase period was determined by Angion’s board of directors. No offering periods or purchasing periods were active as of December 31, 2023. As of December 31, 2023, 68,958 shares under the Company's BoardESPP remain available for purchase and no offerings have been authorized.
Restricted Stock Units
In March 2021, Former Elicio granted restricted stock units (“RSUs”) with service and performance vesting conditions to an employee. The completion of Directors in March 2020. Dr. Yamin's resignation was notthe Merger satisfied the performance vesting criteria and triggered accelerated vesting for all unvested RSUs. As a result, the employee received 41,005 shares on June 1, 2023. To pay for the tax withholdings that were due upon vesting of the RSUs, the employee sold 14,455 shares to any disagreement with the Company, which are held in treasury stock as of December 31, 2023. As of December 31, 2023, there are no RSUs outstanding.
Note 9—Warrants
In accordance with ASC 815, the Board or managementwarrants classified as liabilities are recorded at fair value at the issuance date, with changes in the fair value recognized in the consolidated statements of operations at the end of each reporting period. Refer to Note 4 for changes in the fair value recognized during the periods reported.
In accordance with ASC 815, the warrants classified as equity do not meet the definition of a derivative and are classified in stockholders' equity in the consolidated balance sheets.
There was no warrant activity during the year ended December 31, 2023, other than the assumption of the previously issued Angion warrants by the Company.
The following table summarizes information regarding common stock warrants outstanding at December 31, 2023:
WarrantsWeighted
Average
Exercise
Price
Weighted Average Life (years)
Outstanding at December 31, 2022144,814 $53.59 6.5
Angion warrants assumed3,950 76.00 4.7
Outstanding at December 31, 2023148,764 $54.19 5.5

Note 10—Commitments and Contingencies
Legal Proceedings
From time to time, the Company may be involved in legal proceedings, as well as demands, claims and threatened litigation, which arise in the normal course of its business or otherwise.
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

Note 16—Subsequent Events
On January 4, 2022,The outcome of any future litigation is uncertain. Such litigation, if not resolved, could result in substantial costs to the Company, announced a reductionincluding any costs associated with the indemnification of directors and officers.
The Company may be exposed to litigation in force impacting somewhat less than half ofconnection with its current employees.products under development and operations. The Company’s decisionpolicy is to engage in this reduction resulted from an assessmentassess the likelihood of its internal resources needs, given the results of the Phase 3 study of ANG-3777 in patients at risk for DGF would likely not support a regulatory approval in that population and the Phase 2 study in CSA-AKI would not support a Phase 3 trial in that indication. This reduction was a cost-cutting measure across the organizationany adverse judgments or outcomes related to support the Company’s 2022 primary focus on the clinical development of its investigational asset ANG-3070, a highly selective, oral tyrosine kinase receptor inhibitor in development as a treatment for fibrotic diseases, particularly in the kidney and lung,legal matters, as well as advancing preclinicalranges of probable losses. The Company is not aware of any material legal matters.
License Agreements
In July 2012 and January 2016, Former Elicio licensed certain intellectual property from a university, of which the January 2016 agreement has been amended from time to time. The Company is required to pay certain contractual maintenance and milestone payments related to clinical trials and royalties on product sales over the term of the contract, with minimum annual royalty payments commencing in the calendar year after commercialization. In January 2019, Former Elicio licensed additional intellectual property and terminated a license obtained in July 2012 from the university. The license term for January 2016 license extends until terminated by either party under certain provisions. No commercialization royalties have been achieved.
Future minimum annual maintenance payments are $0.1 million for the year ended December 31, 2023 and for each year thereafter. Future minimum annual payments are due until the termination of the agreement.
Note 11—Leases
Operating Leases
In July 2021, the Company signed an operating lease for office and laboratory space in Boston, Massachusetts (the “Boston Lease”).The Boston Lease commenced in February 2022 with the term set to expire in February 2030. The Boston Lease has rent payments escalating annually, which total $11.1 million in the aggregate. As a result, at the commencement of the Boston Lease, the Company recognized a right-of-use lease asset of $8.0 million with a corresponding lease liability of $8.0 million based on the present value of the minimum rental payments. In addition, the Company will make payments for operating expenses and real estate taxes. In June 2023, the Company secured a letter of credit for the deposit on the Boston Lease and has a deposit in the amount of $0.7 million, which was reported as Restricted Cash on the consolidated balance sheets as of December 31, 2023.
As part of the Merger Agreement, the Company also assumed a lease for clinical and regulatory space in Newton, Massachusetts (the “Newton lease”), comprising approximately 6,157 square feet for approximately $0.2 million per year, under a non-cancelable operating lease through June 30, 2024.
Lease expense for all leases for the years ended December 31, 2023 and 2022 was $1.5 million and $1.2 million, respectively. All expenses are included in operating expenses in the accompanying consolidated statements of operations.
The following table summarizes quantitative information about the Company's operating leases (dollars in thousands):
For the year ended December 31,
20232022
Operating cash flows from operating leases$1,380 $1,106 
Right-of-use assets exchanged for operating lease liabilities$— $8,017 
Weighted-average remaining lease term—operating leases (in years)5.67.2
Weighted-average discount rate—operating leases7.5 %8.0 %
As of December 31, 2023, maturities of lease liabilities were as follows (in thousands):
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

Year Ended December 31,Amounts
2024$1,427 
20251,350 
20261,383 
20271,425 
20281,467 
Thereafter1,765 
Total8,817 
Less present value discount(1,900)
Operating lease liabilities6,917 
Less: operating lease liability, current portion910 
Operating lease liability, noncurrent portion$6,007 
Note 12—Convertible Notes Payable
In October and November 2021, Former Elicio entered into convertible promissory note agreements for an aggregate amount of $14.5 million (the “Convertible Notes”). The Convertible Notes accrue interest at 8% per annum and are payable upon demand at any time on or after October 4, 2022 (the “Demand date”). Interest expense for the year ended December 31, 2022 was $0.9 million.
There were $0.4 million of issuance costs incurred in 2021 and was initially recorded as a discount to the carrying value of the convertible note. Former Elicio recorded interest expense for the year ended December 31, 2022 related to the accretion of the discount to the Convertible Notes due to issuance costs of $0.3 million.
The Convertible Notes included multiple conversion features. Former Elicio evaluated all the conversion features included within the Convertible Note agreements, noting that none of the features was considered to be predominant. Former Elicio also evaluated all conversion features under FASB ASC Topic 815, Derivatives and Hedging, and determined conversion features associated with the qualified and non-qualified financings met the definition of a derivative and require bifurcation from the Convertible Notes. The bifurcated embedded derivative of $2.9 million was recorded as a liability at fair value at the date of issuance based on the probability of occurrence of a triggering event taking place during the term of the Convertible Notes and was recorded as a discount to the carrying value of the Convertible Note. Former Elicio recorded interest expense for the year ended December 31, 2022 related to the accretion of the discount to the Convertible Notes due to the bifurcated embedded derivative of $2.3 million.
During the year ended December 31, 2022, the increase in the fair value of the embedded derivative was determined to be $0.9 million and was recorded as interest expense in the accompanying consolidated statements of operations.
On October 18, 2022, in conjunction with the Series C Preferred Shares issued on this same date, the Convertible Notes Payable totaling $14.5 million and the related accrued interest totaling $1.1 million automatically converted into 1,370,187 Series C Preferred Shares at an 80% discount to the Series C Preferred Share issuance price per share of $14.23, or $11.39 per share. Just prior to settlement, the fair value of the embedded derivative was marked to market a final time to the aggregate value of $3.9 million. Former Elicio recorded an immaterial gain on extinguishment related to the difference in the total of Convertible Notes Payable, total accrued interest and the final fair value of the embedded derivative versus the value of the Series C Preferred Shares issued based on the original issuance price of $14.23 per share.

Note 13—Income Taxes
The components of the Company’s provision for income taxes for the years ended December 31, 2023 and 2022 consists of the following (in thousands):
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

December 31,
20232022
Current:
Federal$— $— 
United States— — 
Foreign— — 
          Total Current— — 
Deferred
Federal7,743 5,162 
State3,116 2,102 
Foreign— — 
Change in valuation allowance(10,859)(7,264)
          Total Deferred— — 
                   Total tax provision$— $— 

The reconciliations between the federal statutory income tax rate and the Company's effective income tax rate were as follows:
Year Ended December 31,
20232022
Statutory federal income tax rate21.0 %21.0 %
State tax, net of federal benefits6.2 %5.1 %
Permanent differences(0.3)%(4.6)%
Federal research and development credits3.1 %2.6 %
State research and development credits0.8 %0.9 %
Other differences0.1 %0.9 %
Change in valuation allowance(30.9)%(25.9)%
Effective income tax rate0.0 %0.0 %
The principal components of the Company's net deferred tax asset at December 31, 2023 and 2022 were as follows (in thousands):
December 31,
20232022
Deferred tax assets (liabilities):
Net operating loss carryforwards$60,696 $19,146 
Research and development tax credit carryovers12,940 3,820 
Capitalized research and development13,686 4,304 
Lease liability1,897 1,949 
Other2,732 611 
ROU Asset(1,800)(1,915)
Property and equipment(33)(37)
Total deferred tax assets90,118 27,878 
Less: Deferred tax asset valuation allowance(90,118)(27,878)
Net deferred tax asset$— $— 

Net operating losses (“NOL”) generated before December 31, 2017 can be carried forward 20 years and carried back two years under the Internal Revenue Code (“IRC”). NOLs arising in tax years ended after December 31, 2017 are limited to 80% of taxable income, only carried forward and carried forward indefinitely. The Company
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

has no income tax expense due to operating losses incurred for the years ended December 31, 2023 and 2022. The Company has provided a valuation allowance for the full amount of the net deferred tax assets as, based on all available evidence, it is considered more likely than not that all the recorded deferred tax assets will not be realized in a future period. The increase in the net deferred tax assets and valuation allowance is primarily due to IND-enabling studies.the reverse merger transaction with Angion in June 2023 (as described in Note 3). For federal income tax purposes the transaction qualified as a tax-free reverse subsidiary merger pursuant to IRC Section 368 (a)(2)(E) and therefore the historical tax basis in the assets acquired and liabilities assumed was carried over upon acquisition. Net deferred tax assets acquired of $50.1 million with an offsetting valuation allowance of $50.1 million are primarily related to pre-merger net operating loss and research and development credits carryovers. At December 31, 2023, Elicio has federal NOLs of $237.8 million, of which $19.1 million was generated before the tax year ended December 31, 2017, and state NOLs of $170.4 million. If not utilized, certain NOLs for federal and state tax purposes will start to expire beginning in 2032. At December 31, 2023, Elicio has $11.1 million and $2.2 million of federal and state research and development credit carryforwards, respectively, that start to expire in 2027.
As the Company has not yet achieved profitable operations, management believes the tax benefits as of December 31, 2023 did not satisfy the realization criteria set forth in ASC Topic 740, Income Taxes and, therefore, has recorded a full valuation allowance for the entire deferred tax asset. The valuation allowance increased in 2023 by $62.2 million due to the increase in the deferred tax assets by the same amount, primarily due to NOL carryforwards. The Company’s effective income tax rate differed from the federal statutory rate primarily due to state taxes and the Company’s full valuation allowance, the latter of which reduced the Company’s effective federal income tax rate to zero.
Ownership changes, as defined in the IRC, may limit the amount of net operating loss carryforwards that can be utilized annually to offset future taxable income pursuant to IRC Section 382 or similar provisions. Subsequent ownership changes could further affect the limitation in future years. The Company has not completed a study to assess whether a change of control has occurred or whether there have been multiple changes of control since the Company’s formation due to the significant complexity and cost associated with such study and because there could be additional changes in control in the future. As a result, the Company is not able to estimate the effect of the change in control, if any, on the Company’s ability to utilize net operating loss and research and development credit carryforwards in the future.
The Company files tax returns in the United States, Australia, California, Connecticut, Delaware, Florida, Iowa, Massachusetts, Missouri, New Hampshire, New Jersey, and Tennessee. All tax years from 2020 to 2023 remain open to examination by the major taxing jurisdictions to which the Company is subject, as carryforward attributes generated in years past may still be adjusted upon examination by the Internal Revenue Service (“IRS”) or other authorities if they have or will be used in a future period. To its knowledge, the Company is not currently under examination by the IRS or any other jurisdictions for any tax years.
As of December 31, 2023, the Company had $4.1 million of uncertain tax positions related to prior research tax credits that may not be substantiated upon audit. The Company does not anticipate that uncertain tax positions will decrease within the next 12 months. The Company has elected to recognize interest and penalties related to income tax matters as a component of income tax expense, of which no interest or penalties were recorded for the years ended December 31, 2023 and 2022.
Note 14—Employee Benefit Plan
Employee Benefit Plan
The Company provides a retirement savings plan through the Vendantra Pharmacueticals Inc. 401(k) Plan (the “Elicio Retirement Plan”), subject to certain limitations. As allowed under Section 401(k) of the IRC, the Elicio Retirement Plan allows tax deferred salary deductions for eligible employees. An employee’s interest in his or her salary deferral contributions is 100% vested when contributed.
Pursuant to the Merger Agreement, the Company assumed the retirement savings plan sponsored by Angion (the “Angion Retirement Plan”). The Angion Retirement Plan is intended to qualify for favorable tax treatment under Section 401(a) of the IRC, and contains a cash or deferred feature that is intended to meet the requirements of Section 401(k) of the IRC. Currently, no employees are contributing under the Angion Retirement Plan.
Note 15—Net Loss Per Share
The Company has reported losses since inception and has computed basic net loss per share attributable to common stockholders by dividing net loss attributable to common stockholders by the weighted-average number of shares of common stock outstanding for the period, without consideration for potentially dilutive securities. The Company computes diluted net loss per share of common stock after giving consideration to all potentially dilutive
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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)
On February 25,
shares of common stock, including options to purchase common stock and preferred stock outstanding during the period determined using the treasury-stock and if-converted methods, except where the effect of including such securities would be antidilutive. Because the Company has reported net losses since inception, these potential shares of common stock and preferred stock have been anti-dilutive and basic and diluted loss per share were the same for all periods presented.
Basic and diluted net loss per share attributable to common stockholders was calculated at December 31, 2023 and 2022 as follows (in thousands, except share and per share data):
Year Ended December 31,
20232022
Numerator:
Net loss$(35,195)$(28,208)
Denominator:
Weighted-average shares used in computing net loss per share, basic and diluted5,056,225315,998
Net loss per share, basic and diluted$(6.96)$(89.27)
The table below provides potentially dilutive securities not included in the calculation of the diluted net loss per share because to do so would be anti-dilutive:
December 31,
20232022
Convertible preferred stock4,997,920
Shares issuable upon exercise of stock options1,305,924854,076
Shares issuable upon the exercise of warrants148,764144,814
Unvested Common Stock1,9337,240
Total1,456,6216,004,050

Note 16—Related Party Transactions
Consulting Agreement
The Company paid $0.7 million and $0.4 million for the years ended December 31, 2023 and 2022, respectively, for consulting services provided by an entity affiliated with the Company’s former interim chief financial officer and former board member.
Subscription Agreement
In December 2023, the Company entered into a Separation Agreementsubscription agreement (the “December Subscription Agreement”) with Itzhak D. Goldberg, M.D.GKCC, LLC (the “Purchaser”), who formerly served as Executive Chairman and Chief Scientific Officer and currently serves asan entity which is controlled by a director of the Company, providing for the issuance and Chairman Emeritus on our Board.sale by the Company to the Purchaser of an aggregate of 1,213,000 shares of the Company’s common stock, par value $0.01 per share, at a purchase price per share of $5.81 (the “December Offering”). The gross proceeds to the Company from the December Offering was approximately $7.0 million. The closing of the December Offering occurred in December 2023. Upon closing of the December Offering, the Purchaser became a greater than 10% holder of the Company’s shares outstanding.
Pursuant to the December Subscription Agreement, the Company is obligated, among other things, to file a registration statement with the SEC by March 31, 2024 for purposes of registering the shares for resale by the Purchaser, and use its commercially reasonable efforts to have the registration statement declared effective no later than 30 days after filing such registration statement with the SEC, or in the event the SEC reviews and has written comments to the registration statement, within 90 days following the receipt of such written comments. The December Subscription Agreement contains customary terms and conditions for a transaction of this type, including certain customary indemnification rights and certain customary cash penalties on the Separation Agreement, Dr. Goldberg will receive severance benefitsCompany for its failure to satisfy specified filing and effectiveness time periods.


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ELICIO THERAPEUTICS, INC.
Notes to Consolidated Financial Statements (Continued)

Note 17—Subsequent Events
The Company has completed an evaluation of all subsequent events after the audited consolidated balance sheet date as of December 31, 2023 through the date these consolidated financial statements were issued to ensure that these consolidated financial statements include appropriate disclosure of events both recognized in the consolidated financial statements as of December 31, 2023, and events which occurred subsequently but were not recognized in the consolidated financial statements. Non-recognizable subsequent events are summarized below.
ATM Program
Subsequent to December 31, 2023, the Company issued and sold a total of 615,363 shares of common stock under the ATM Program for aggregate net sale proceeds of approximately $1.1 million. Under our Amended and Second Restated 2015 Equity Incentive Plan and our 2021 Incentive Award Plan, Dr. Goldberg will continue to vest his PSUs and stock options and exercisability of his options, so long as he remains in continuous service with the Company as a director on the Board or otherwise.$5.1 million after deducting sales commissions.
OnSubscription Agreement
In March 1, 2022,2024, the Company entered into a Separation Agreementsubscription agreement (the “March Subscription Agreement”) with Elisha Goldberg, former employeethe Purchaser, an entity controlled by a member of the board of directors of the Company and sonwhich owns greater than 10% of Itzhak D. Goldberg, M.D., who currently serves as a director and Chairman Emeritus on the Company’s Board.Pursuantshares outstanding, providing for the issuance and sale by the Company to the Purchaser of pre-funded warrants (the “Pre-Funded Warrants”) to purchase up to 1,032,702 shares of the Company’s common stock, at a purchase price per Pre-Funded Warrant of $5.81 (the “March Offering”). The March Offering closed on March 19, 2024 (the “March Offering Closing Date”). Each Pre-Funded Warrant is exercisable at any time on or after the March Offering Closing Date at an exercise price equal to $0.01 per share, subject to adjustments as provided under the terms of the SeparationPre-Funded Warrant, subject to a post-exercise beneficial ownership limitation of 19.99%, unless Stockholder Approval (defined below) is obtained. The gross proceeds to the Company from the March Offering was approximately $6.0 million.

Pursuant to the March Subscription Agreement, Mr. Goldberg will receive severance benefitsthe Company is obligated, among other things, to file a registration statement with the SEC by June 30, 2024 for purposes of approximately $0.5 million. Mr. Goldberg will alsoregistering the shares of the Company’s common stock issuable upon exercise of the Pre-Funded Warrants (the “Pre-Funded Warrant Shares”) for resale by the Purchaser, and to use its commercially reasonable efforts to have the rightregistration statement declared effective no later than 30 days after filing such registration statement with the SEC, or in the event the SEC reviews and has written comments to exercisethe registration statement, within 90 days following the receipt of such written comments. The March Subscription Agreement contains customary terms and conditions for a transaction of this type, including certain customary indemnification rights and certain customary cash penalties on the Company for its failure to satisfy specified filing and effectiveness time periods.

In addition, pursuant to the March Subscription Agreement, no later than six months following the March Offering Closing Date, the Company has agreed to use commercially reasonable efforts to obtain such approval as may be required by the applicable rules and regulations of The Nasdaq Stock Market (or any vestedsuccessor entity) from the stockholders of the Company with respect to a change of control of the Company pursuant to Section 5635(b) of the Listing Rules of The Nasdaq Stock Market resulting from beneficial ownership in excess of 19.99% of the outstanding common stock options he may have received under our Amended and Second Restated 2015 Equity Incentive Plan or our 2021 Incentive Award Plan until December 31, 2022, which extendedof the exercise period by 11 months.Company upon the issuance of the Pre-Funded Warrant Shares (“Stockholder Approval”).
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Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
None.
Item 9A. Controls and Procedures

Definition and Limitations of Disclosure Controls
Our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended (the “Exchange Act”)) are controls and other procedures that are designed to ensure that information required to be disclosed in our reports filed under the Exchange Act, such as this Annual Report on Form 10-K, is recorded, processed, summarized and reported within the time periods specified in the SEC’s rules and forms. Disclosure controls and procedures are also designed to ensure that such information is accumulated and communicated to our management, including our principal executive officer and principal financial officer, as appropriate to allow timely decisions regarding required disclosure. Our management evaluates these controls and procedures on an ongoing basis.
There are inherent limitations to the effectiveness of any system of disclosure controls and procedures. These limitations include the possibility of human error, the circumvention or overriding of the controls and procedures and reasonable resource constraints. In addition, because we have designed our system of controls based on certain assumptions, which we believe are reasonable, about the likelihood of future events, our system of controls may not achieve its desired purpose under all possible future conditions. Accordingly, our disclosure controls and procedures provide reasonable assurance, but not absolute assurance, of achieving their objectives.

Evaluation of Disclosure Controls and Procedures

Our management, with the participation of our President and Chief Executive Officer and our Chief Financial Officer, our principal executive officer and principal accounting and financial officer, respectively, have evaluated the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act) as of December 31, 2021.2023.
Disclosure controls and procedures are controls and other procedures that are designed to ensure that information required to be disclosed in our reports filed or submitted under the Exchange Act is recorded, processed, summarized and reported, within the time periods specified in the SEC’s rules and forms. Disclosure controls and procedures include controls and procedures designed to ensure that information required to be disclosed in our reports filed under the Exchange Act is accumulated and communicated to management, including our President and Chief Executive Officer and our Chief Financial Officer, to allow timely decisions regarding required disclosure. Based on the evaluation of our disclosure controls and procedures, our President and Chief Executive Officer and our Chief Financial Officer concluded that our disclosure controls and procedures were not effective as of December 31, 2021 due to the2023 as a result of our material weaknesses in our internal control over financial reporting described below. In light of this fact,reporting.

However, our management, has performed additional analyses, reconciliations,including our Chief Executive Officer and other post-closing procedures andour Chief Financial Officer, has concluded that, notwithstanding the identified material weaknesses in our internal control over financial reporting, the consolidated financial statements for the periods covered by and included in this Annual Report on Form 10-K fairly present, in all material respects, our financial position, results of operations and cash flows for the periods presented in conformity with U.S. GAAP.
Changes in Internal Control Over Financial Reporting
Except for the changes in connection with the ongoing remediation of the previously identified material weakness discussed below, there has beenThere was no change in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f)) under the Exchange Act) that occurred during the year ended December 31, 2021,2023, that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting.reporting, except as follows:
In
Material Weakness Remediation Plan
As previously reported, in connection with the preparation of our consolidated financial statements, we identified control deficiencies in the design and operation of our internal control over financial reporting that constituted material weaknesses. A material weakness is a deficiency, or a combination of deficiencies, in internal control over financial reporting such that there is a reasonable possibility that a material misstatement of our financial statements will not be prevented or detected on a timely basis.
The material weaknesses identified in our internal control over financial reporting related to (i) insufficient resources with knowledge and expertise in U.S. GAAP to properly evaluate certain complex transactions, including debt instruments and equity instruments; and (ii) insufficient financial reporting and close controls to ensure that incurred expenses are accrued at period end and deliverables from third party contractors are reviewed for accuracy.accuracy; and (iii) insufficient resources to ensure that calculations used in financial reporting are properly reviewed, including EPS and WASO calculations.
During 2021, we took a number of actionsWe initiated several steps to remediate these material weaknesses, including:
engaging SEC compliance and technical accounting consultants to assist in evaluating transactions for conformity with U.S. GAAP;
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hiring additional finance and accounting personnel to augment accounting staff and to provide more resources for complex accounting matters and financial reporting; and
strengthening our financial reporting and close relating to incurred expenses by ensuring our data capture procedures are clearly defined and that responsible personnel, including supervisory personnel, have adequate training regarding the process and expectation.
We are still in the process of implementing these controls. We intend to continue to take stepsAlthough we have initiated efforts to remediate these material weaknesses, the material weaknesses through formalizing documentationhave not been fully remediated as of policies and procedures and further evolving our accounting processes.
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TableDecember 31, 2023. Our remediation efforts are intended to address the identified material weaknesses. Management is committed to continuous improvement of Contents
While we believe that these efforts will improve our internal control over financial reporting the design and implementation of our remediation is ongoing and will require validation and testing of the design and operating effectiveness ofcontinue to diligently review our internal controlscontrol over a sustained period of financial reporting cycles. The actionsreporting. However, we cannot assure you that we are taking are subject to ongoing senior management review, as well as audit committee oversight. We will not be able to conclude whether the steps we are taking will fully remediatesuccessful in remediating the material weaknesses inwe identified or that our internal control over financial reporting, until we have completed our remediation efforts and subsequent evaluation of their effectiveness.as modified, will enable us to identify or avoid material weaknesses in the future.
Management’s Report on Internal Control Over Financial Reporting
Our management is responsible for establishing and maintaining adequate internal control over financial reporting as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act. Our internal control over financial reporting is a process designed by, or under the supervision of, the Company’s principal executive and principal accounting and financial officers and effected by the Company’s board of directors, management and other personnel to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with GAAP. Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements.
Our management assessed the effectiveness of our internal control over financial reporting as of December 31, 2021.2023. In making this assessment, management used the criteria set forth by the Committee of Sponsoring Organizations of the Treadway Commission (COSO)(“COSO”) in Internal Control-Integrated Framework (2013 framework). Based on our assessment, management concluded our internal control over financial reporting was not effective as of December 31, 2021,2023, based on the COSO criteria, due to the existence of the material weaknesses.criteria.
Inherent Limitation on the Effectiveness Over Financial Reporting
The effectiveness of any system of internal control over financial reporting, including ours, is subject to inherent limitations, including the exercise of judgment in designing, implementing, operating, and evaluating the controls and procedures, and the inability to eliminate misconduct completely. Accordingly, any system of internal control over financial reporting, including ours, no matter how well designed and operated, can only provide reasonable, not absolute assurances. In addition, projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate. We intend to continue to monitor and upgrade our internal controls as necessary or appropriate for our business, but there can be no assurance that such improvements will be sufficient to provide us with effective internal control over financial reporting.
Item 9B. Other Information
None.During the three months ended December 31, 2023, no director or officer of the Company adopted, modified or terminated a “Rule 10b5-1 trading arrangement” or “non-Rule 10b5-1 trading arrangement,” as each term is defined in Item 408(a) of Regulation S-K.

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections
None.Not applicable.
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Part III
Item 10. Directors, Executive Officers and Corporate Governance
Management
Executive Officers
The following table sets forth information regardingrequired by this Item is incorporated herein by reference to the information that will be contained in our executive officersproxy statement related to the 2024 Annual Meeting of Stockholders, which we intend to file with the Securities and directors as of March 1, 2022:
NameAgePosition(s)
Executive Officers and Employee Directors:
Jay R. Venkatesan, M.D.50President and Chief Executive Officer and Chairman of the Board
John F. Neylan, M.D.68Executive Vice President, Chief Medical Officer and Head of Research
Jennifer J. Rhodes, J.D.51Executive Vice President, Chief Business Officer, General Counsel, Chief Compliance Officer and Corporate Secretary
Gregory S. Curhan60Chief Financial Officer
Non-Employee Directors:
Victor F. Ganzi(1)(2)(3)
75Director, Lead Independent Director
Itzhak D. Goldberg, M.D.(4)
73Director and Chairman Emeritus
Allen R. Nissenson, M.D.(1)(2)(3)
75Director
Gilbert S. Omenn, M.D., Ph.D.(1)(2)(3)
80Director
Karen J. Wilson(1)(2)(3)
58Director
________________________
(1) MemberExchange Commission within 120 days of the audit committee.
(2) Memberend of the compensation committee.
(3) Member of the nominating and corporate governance committee.
(4) Dr. Goldberg resigned his employment in February 2022 and no longer serves as an Executive Officer of Angion. Dr. Goldberg continues to serve as a Director and Chairman Emeritus.
Executive Officers and Employee Directors
Jay R. Venkatesan, M.D., President, Chief Executive Officer and Chairman. Dr. Venkatesan was appointed Chairman of the Board in January 2022, and he has been our President and Chief Executive Officer and director since May 2018. Dr. Venkatesan has served as a Managing Partner of Alpine BioVentures, an investment firm, since July 2015. From July 2015 to August 2018, Dr. Venkatesan served as President of Alpine Immune Sciences, an immunotherapy company that he co-founded as a Managing Partner of Alpine BioVentures, and also served as its Chief Executive Officer from July 2015 to June 2016. Additionally, as Managing Partner of Alpine BioVentures, from January 2014 to August 2014, Dr. Venkatesan served as Founder and Chief Executive Officer of Alpine BioSciences, a biotechnology company, which was acquired by Cascadian Therapeutics, where he then served as Executive Vice President and General Manager from August 2014 to May 2015 (subsequently acquired by Seagen, Inc.). Since January 2008, Dr. Venkatesan has served as the founder and managing member of Ayer Capital, a global healthcare fund. Prior to that, he served as a director at Brookside Capital, part of Bain Capital, where he co-managed healthcare investments. He was also a consultant at McKinsey & Co., a consulting firm, and a venture investor with Patricof & Co. Ventures (now Apax Partners), an investment firm. Dr. Venkatesan has served on the board, of Alpine Immune Sciences, Inc. (Nasdaq: ALPN) since June 2015. Dr. Venkatesan previously served on the board of Exicure Inc. (Nasdaq: XCUR) from March 2014 to December 2020 and Iovance Biotherapeutics Inc. (Nasdaq: IOVA) from September 2013 to March 2018. He has an M.D. from the University of Pennsylvania School of Medicine, an M.B.A. from the Wharton School of the University of Pennsylvania, and a B.A. from Williams College. We believe that Dr. Venkatesan's leadership experience and investment experience in the biopharmaceutical industry qualify him to serve as a member of our board of directors.

John F. Neylan, M.D. Dr. Neylan was appointed Executive Vice President and Head of Research in March 2022, and he has served as our Chief Medical Officer since December 2018. From April 2015 to December 2018, Dr. Neylan served as Chief Medical Officer of Keryx, a biopharmaceutical company focused on nephrology. From May 2008 to April 2015, Dr. Neylan served as Senior Vice President, Clinical Development, at Genzyme
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Corporation, a biopharmaceutical company focusing on specialty metabolic diseases. From 2000 to 2008, Dr. Neylan served as Vice President, Research and Development for Wyeth Research, a pharmaceutical company, overseeing the clinical development of transplantation therapeutics and providing medical affairs support to the transplant franchise. Dr. Neylan has also held prestigious positions in academia, including Professor of Medicine at Emory University and Assistant Professor of Medicine at University of California, Davis, serving at both institutions as Medical Director of the respective Renal Transplant Programs, with oversight of the clinical research programs. Dr. Neylan has a B.S. from Duke University and an M.D. from Rush Medical School in Chicago. He completed his Internal Medicine residency at Vanderbilt University and fellowships in Nephrology and in Transplantation and Immunogenetics at Brigham and Women's Hospital, Harvard University. He was formerly the President of the American Society of Transplantation, past Board Member of the National Kidney Foundation and a past Industry Representative on the FDA Cardiovascular and Renal Drugs Advisory Committee.

Jennifer J. Rhodes, J.D. Ms. Rhodes was appointed Executive Vice President and Chief Business Officer in March 2022 and she has served as, General Counsel, Chief Compliance Officer and Corporate Secretary since January 2020. In February 2019, Ms. Rhodes also became a director of Legal Aid at Work, a non-profit legal services organization. Ms. Rhodes previously served as General Counsel and Corporate Secretary at Adamas Pharmaceuticals, Inc., a public pharmaceutical company, from April 2016 until January 2020, during which time she also served as Chief Compliance Officer since August 2016 and Chief Business Officer since January 2017. Prior to that, Ms. Rhodes served as General Counsel at Medivation, Inc., a biopharmaceutical company, from June 2012 to September 2015, where she was responsible for Medivation's legal matters, and also served as Corporate Secretary from April 2013 to September 2015 and as Chief Compliance Officer from July 2012 to October 2014. From May 2006 to June 2012, Ms. Rhodes was an Assistant General Counsel at Pfizer Inc., a biopharmaceutical company, where she supported the U.S. Primary Care Business and its Primary Care Medicines Development Group and served as a global product lead for Pfizer Inc.'s primary care medicines. Prior to joining Pfizer Inc., she was an associate in the regulatory law and international trade practice areas at Weil, Gotshal & Manges, LLP from October 2000 to April 2006. Ms. Rhodes has a J.D. from Wake Forest University School of Law and a B.A. in Economics from Newcomb College of Tulane University.

Gregory S. Curhan. Mr. Curhan has served as our Chief Financial Officer since June 2020 through his capacity as a partner at FLG Partners, LLC (FLG Partners), a Silicon Valley chief financial officer services firm. Prior to joining FLG Partners, LLC, Mr. Curhan was Chief Financial Officer and Senior Vice President Corporate Development of Providence Medical Technology, a venture-backed medical device manufacturer, December 2016 until January 2020. Prior to that, Mr. Curhan was a Business Development Officer at Brighton Jones, a financial planning company, from December 2012 to December 2016. Mr. Curhan has a B.A. in Economics from Dartmouth College.
Non-Employee Directors
Victor F. Ganzi. Mr. Ganzi has been a member of our board of directors since April 2018, and lead independent director since February 2021. He has served as Non-Executive Chairman of the board of directors of Willis Towers Watson (Nasdaq: WTW), a global advisory, broking and solutions company, since January 2019 and as a director since January 2016. Previously, he served as a director of Towers Watson beginning on January 1, 2010, as Chairman of Towers Watson's Audit Committee, and a member of its Nominating and Governance Committee. Mr. Ganzi is presently a consultant and corporate director, serving on the public company board of Aveanna Healthcare Holdings Inc., a provider of pediatric and adult home healthcare and hospice care since 2016, and serving on the boards of numerous private and not-for-profit organizations, including PGA Tour, Inc., the Partnership to End Addiction, the Whitney Museum of American Art and the Madison Square Boys and Girls Club. Mr. Ganzi was the President and Chief Executive Officer of The Hearst Corporation, a private diversified communications company, from 2002 to 2008. He served as Hearst's Executive Vice President from 1997 to 2002 and as its Chief Operating Officer from 1998 to 2002. Prior to joining Hearst in 1990, Mr. Ganzi was the managing partner at the international law firm of Rogers & Wells (now part of Clifford Chance). Mr. Ganzi previously served as a director of Gentiva Health Services, Inc., Wyeth and Hearst-Argyle Television, Inc. Mr. Ganzi has a B.S. in Accounting summa cum laude, from Fordham University, a J.D. from Harvard Law School and an L.L.M. in Taxation from New York University. We believe that Mr. Ganzi's years of experience serving on boards and legal expertise qualify him to serve as a member of our board of directors.
Itzhak D. Goldberg, M.D., Dr. Goldberg was appointed Chairman Emeritus in January 2022, after having been a director and Chairman of the Board since March 2018. Dr. Goldberg also served as Executive Chairman and Chief Scientific Officer between March 2018 and March 2022, after serving as our Chairman, President, Chief Executive Officer and Scientific Director since our founding in April 1998. Dr. Goldberg was formerly a faculty
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member at Harvard Medical School, Radiation Oncologist-in-Chief for the North Shore-LIJ (Northwell) Health System, and Professor at the Albert Einstein College of Medicine. He is a Fellow of the American College of Radiology. Dr. Goldberg has an M.D. from Albert Einstein College of Medicine, was a postdoctoral research fellow at Harvard Medical School and was subsequently trained as a radiation oncologist at the Harvard Joint Center for Radiation Therapy. We believe that Dr. Goldberg's extensive experience in the biopharmaceutical industry qualifies him to serve as a member of our board of directors.

Allen R. Nissenson, M.D. Dr. Nissenson has been a member of our board of directors since January 2020. He completed serving as the EmeritusChief Medical Officer of DaVita Kidney Care in January 2022, where he has served since January 2020 and where he previously served as Chief Medical Officer from August 2008 to January 2020. He is currently an Emeritus Professor of Medicine at the David Geffen School of Medicine at UCLA, where he has served since August 2008 and where he previously served as Director of the Dialysis Program from July 1977 to August 2008 and Associate Dean from July 2005 to August 2008. Dr. Nissenson is also currently on the board of directors of Rockwell Medical Inc., a public biopharmaceutical company, which he joined in June 2020 and Diality, a private technology development company. Dr. Nissenson is a past chair of Kidney Care Partners and past co-chair of the Kidney Care Quality Alliance. He is a former president of the Renal Physicians Association (RPA) and current member of the Government Affairs Committee. Dr. Nissenson also previously served as president of the Southern California End-Stage Renal Disease Network, as well as chair of the Medical Review Board. He served as a Robert Wood Johnson Health Policy Fellow of the National Academy of Medicine from 1994 to 1995 and worked in the office of the late Senator Paul Wellstone. Dr. Nissenson has an M.D. from Northwestern University Medical School and is the recipient of various awards, including the President's Award of the National Kidney Foundation, the Lifetime Achievement Award in Hemodialysis, the American Association of Kidney Patients' (AAKP) Medal of Excellence Award and, in 2017, the RPA Distinguished Nephrology Service Award. We believe that Dr. Nissenson's years of experience in the healthcare industry qualify him to serve as a member of our board of directors.

Gilbert S. Omenn, M.D., Ph.D. Dr. Omenn has been a member of our board of directors since January 2020. Since 1997, Dr. Omenn hasbeen a faculty member at the University of Michigan, where he is currently the Harold T. Shapiro Distinguished University Professor of Computational Medicine & Bioinformatics, Internal Medicine, Human Genetics, and Public Health. Earlier, he was the dean of the School of Public Health and Community Medicine and professor of medicine at the University of Washington. Dr. Omenn served as Executive Vice President for Medical Affairs of the University of Michigan and as Chief Executive Officer of the University of Michigan Health System from 1997 to 2002.From 1977 to 1981 he was associate director of the White House Office of Science & Technology Policy and then the Office of Management & Budget. Dr. Omenn is a member of the National Academy of Medicine and the American Academy of Arts and Sciences. He chaired the Presidential/Congressional Commission on Risk Assessment and Risk Management, the NAS/NAE/IOM Committee on Science, Engineering, and Public Policy, and the Advisory Committee for the Agency for Toxic Substances and Disease Registry. He served on the National Commission on the Environment, the NIH Scientific Management Review Board, and the CDC Director's Advisory Committee. He is a past president of the American Association for the Advancement of Science.Since 2014, Dr. Omenn has served as a director of Galectin Therapeutics Inc., a biotechnology company (Nasdaq: GALT), and since 2020 as a director of Amesite Inc, an AI-based educational technology company (Nasdaq: AMST). Dr. Omenn previously served as a director of Amgen, Inc. for 27 years and Rohm & Haas Company for 22 years. Dr. Omenn was a director of Esperion Therapeutics (Nasdaq: ESPR) from August 2014 to May 2018. He is a director of the Hastings Center for Bioethics and the Center for Public Integrity. Dr. Omenn has a B.A. summa cum laude from Princeton University, M.D. magna cum laude from Harvard Medical School and Ph.D. in genetics from the University of Washington. We believe that Dr. Omenn's years of experience in the healthcare industry qualify him to serve as a member of our board of directors.
Karen J. Wilson. Ms. Wilson has been a member of our board of directors since April 2020. Ms. Wilson is also currently a member of the boards of directors of Connect Biopharma, LAVA Therapeutics and Vaxart, Inc. Ms. Wilson previously served as Senior Vice President of Finance at Jazz Pharmaceuticals plc, a biopharmaceutical company, until September 2020 after serving as Principal Accounting Officer and Vice President of Finance. Prior to joining the Jazz Pharmaceuticals organization in February 2011, she served as Principal Accounting Officer and Vice President of Finance at PDL BioPharma, Inc., a life sciences company. She also previously served as a Principal at the consulting firm of Wilson Crisler LLC, Chief Financial Officer of ViroLogic, Inc., a biosciences company, Chief Financial Officer and Vice President of Operations for Novare Surgical Systems, Inc., a medical device manufacturer, and as a consultant and auditor for Deloitte & Touche LLP, a professional services firm. Ms. Wilson is a Certified Public Accountant and received a B.S. in Business from the University of California, Berkeley.
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We believe that Ms. Wilson is qualified to serve on our Board due to her extensive background in financial and accounting matters for public companies and her leadership experience in the life science industry.

Delinquent Section 16(a) Reports
Section 16(a) of the Exchange Act requires our directors, executive officers, and persons holding more than 10% of our common stock to report their initial ownership of the common stock and other equity securities and any changes in that ownership in reports that must be filed with the SEC. The SEC has designated specific deadlines for these reports, and we must identify in our Annual Report on Form 10-K those persons who did not file these reports when due.
We filed reports on behalf of our directors, executive officers and 10% holders during the year ended December 31, 2021. Such reports were filed consistent with the reporting obligations of Section 16(a) of the Exchange Act, except that untimely reports were filed on behalf of Dr. Goldberg and Dr. Venkatesan on November 17, 2021 and December 17, 2021, respectively, reporting the shares that were withheld to satisfy tax or other government withholding obligations in connection with the vesting of PSUs.

Audit Committee

Our audit committee oversees our corporate accounting and financial reporting process.

The members of our audit committee are Karen Wilson, Victor Ganzi, Allen Nissenson and Gilbert Omenn. Ms. Wilson serves as the chairperson of the committee. All members of our audit committee meet the requirements for financial literacy under the applicable rules and regulations of the SEC and The Nasdaq Stock Market. Our board of directors has determined that Ms. Wilson is an audit committee financial expert as defined under the applicable rules of the SEC and has the requisite financial sophistication as defined under the applicable rules and regulations of The Nasdaq Stock Market. Under the rules of the SEC, members of the audit committee must also meet heightened independence standards. Our board of directors has determined that each of Ms. Wilson, Mr. Ganzi, Dr. Nissenson and Dr. Omenn are independent under the applicable rules of the SEC and The Nasdaq Stock Market. The audit committee operates under a written charter that satisfies the applicable standards of the SEC and The Nasdaq Stock Market.
Procedures by Which Security holders May Recommend Nominees to the Board of Directors
The Nominating and Corporate Governance Committee of the Board has adopted procedures for considering director candidates recommended by stockholders. Stockholders who wish to recommend individuals for consideration by the Committee as candidates for potential election by the Board as directors, can deliver a written recommendation to the Corporate at Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, New York 11553, at least 120 days prior to the anniversary date of the mailing of the proxy statement for the last annual meeting of stockholders and must include the following information: name and address of the nominating stockholder; a representation that the nominating stockholder is a record holder; a representation that the nominating stockholder intends to appear in person or by proxy at the annual meeting to nominate the person or persons specified; information regarding each nominee that would be required to be included in a proxy statement; a description of any arrangements or understandings between the nominating stockholder and the nominee; and the consent of each nominee to serve as a director, if elected.
The Nominating and Corporate Governance Committee will evaluate candidates recommended by a stockholder in the same manner as candidates identified any other person, including members of the Board.

Code of Business Conduct and Ethics
Our Board of directors has adopted a code of business conduct and ethics that applies to all of our employees, officers and directors, including those officers responsible for financial reporting. The code of business conduct and ethics is available on our website. We intend that any amendments to the code, or any waivers of its requirements, will be disclosed on our website.
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Item 11. Executive Compensation
The following is a discussion and analysis of compensation arrangements of our named executive officers (NEOs). This discussion contains forward looking statements that are based on our current plans, considerations, expectations and determinations regarding future compensation programs. Actual compensation programs that we adopt may differ materially from currently planned programs as summarized in this discussion. As an “emerging growth company” as defined in the JOBS Act, we are not required to include a Compensation Discussion and Analysis section and have elected to comply with the scaled disclosure requirements applicable to emerging growth companies.
We seek to ensure that the total compensation paid to our executive officers is reasonable and competitive. Compensation of our executives is structured around the achievement of individual performance and near-term corporate targets as well as long-term business objectives.
Our NEOs for fiscal year 2021 were as follows:
Jay R. Venkatesan, M.D., President and Chief Executive Officer and Chairman of the Board(1) ;
Itzhak Goldberg, Director and Chairman Emeritus(2)
John Neylan, Executive Vice President, Chief Medical Officer and Head of Research
________
(1) Dr. Venkatesan was appointed Chairman of the Board in January 2022.
(2) After serving as Executive Chairman and Chief Scientific Officer for Angion during the year ended December 31, 2021. Dr. Goldberg resigned his employment in February 2022, and no longer serves as an Executive Officer of Angion.

2021 Summary Compensation Table
The following table sets forth total compensation paid to our NEOs for the fiscal year ending on December 31, 2021 and, with respect to Dr. Venkatesan, 2020. Neither Dr. Goldberg or Dr. Neylan were named executive officers in 2020 and, accordingly, their compensation for 2020 is omitted.
Name and Principal PositionYear
Salary
($)
Bonus(1)
($)
Option Awards(2) ($)
Total (3)
($)
Jay R. Venkatesan, M.D., President and Chief Executive Officer and Chairman of the Board(4)
2021587,100 — 1,952,099 2,539,199 
2020570,000 194,800 629,598 1,394,398 
Itzhak D. Goldberg, M.D.,
Executive Chairman and Chief Scientific Officer(5)
2021484,018 — 763,863 1,247,881 
John F. Neylan, M.D.,
Executive Vice President, Chief Medical Officer and Head of Research (6)
2021468,650 — 763,863 1,232,513 

(1)The bonus column includes discretionary annual bonuses paid to each of our NEOs in connection with their service in the applicable fiscal year. For fiscal year 2020, the bonuses were paid in March 2021. Please see the descriptions of the bonuses paid to our NEOs under "2021 Bonuses" below, including target amounts for the discretionary annual bonuses.
(2)Amounts shown represents the grant date fair value of options granted as calculated in accordance with ASC Topic 718. See Note 2 of the financial statements included incovered by this Annual Report on Form 10-K for the assumptions used in calculating this amount.
(3)NEOs received no compensation other than salaries, bonuses, and stock option awards.
(4)Dr. Venkatesan was appointed Chairmanpursuant to General Instruction G(3) of the Board in January 2022.
(5)After serving as Executive Chairman and Chief Scientific Officer for Angion during the year ended December 31, 2021, Dr. Goldberg resigned his employment in February 2022, and no longer serves as an Executive Officer of Angion. Dr. Goldberg continues to serve as a Director and Chairman Emeritus.
(6)Dr. Neylan was appointed Executive Vice President and Head of Research in March 2022, and continues to serve as Chief Medical Officer.

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Narrative to Summary Compensation Table
2021 Salaries
Our NEOs each receive a base salary to compensate them for services rendered to our company. The base salary payable to each named executive officer is intended to provide a fixed component of compensation reflecting the executive's skill set, experience, role and responsibilities. Dr. Venkatesan's base salary in 2020 was $570,000 and was increased to $587,100, effective as of January 1, 2021. Dr. Venkatesan current annual salary, effective January 1, 2022 is $608,000. Dr. Goldberg's base salary in 2020 was $469,920 and was increased in 2021 to $484,018, effective as of January 1, 2021. Dr. Goldberg is no longer employed by Angion. Dr. Neylan's base salary in 2020 was $455,000 and was increased to $468,650, effective as of January 1, 2021. Dr. Neylan’s current annual salary, effective January 1, 2022, is $485,100. Our board of directors and compensation committee may adjust base salaries from time to time in their discretion.
2021 Bonuses
Our NEOs did not receive a 2021 discretionary cash bonus. We paid each of our NEOs a discretionary cash bonus in 2021 in connection with their contributions to Angion in 2020, based upon their bonus targets, or 50%, 40% and 40% of Dr. Venkatesan's, Dr. Goldberg’s and Dr. Neylan's base salary, respectively.
Equity-Based Compensation
In February 2021, we granted each of Dr. Venkatesan, Dr. Goldberg and Dr. Neylan an option to purchase 178,920, 70,012 and 70,012 shares of our common stock, respectively, under our 2021 Incentive Award Plan (the “2021 Plan”). Each of Dr. Venkatesan's, Dr. Goldberg’s and Dr. Neylan’s options vest as to 1/48th of the shares subject to the option on each monthly anniversary of February 5, 2021, subject to the applicable NEO being employed or in continuous service to us as defined in the 2021 Plan through such vesting date. Upon our IPO in February 2021, Dr. Venkatesan’s and Dr. Goldberg’s performance-based restricted stock units (PSUs) met the performance condition, an initial public offering as defined in the Amended and Second Restated 2015 Equity Award Plan (the “2015 Plan”). Accordingly, the vesting of such PSUs in three equal parts, with the first part vesting commenced upon the IPO in February 2021, the second part vesting for each Dr. Venkatesan and Dr. Goldberg on June 24, 2021, and the third part to vest for each on June 24, 2022. As of December 31, 2021, 371,020 PSUs have been vested.
Other Elements of Compensation
Retirement Savings and Health and Welfare Benefits
On January 1, 2021, we implemented a 401(k) Retirement Savings Program through a third-party provider. Our NEOs are eligible to participate our 401(k) Program on the same terms as other full-time employees. We match 100% of the first 3% of a participant's annual eligible contributions to their 401(k) plan, and 50% of annual eligible contribution between 3% and 5%.We terminated our simple IRA plan for our employees, including our named executive officers, who satisfy certain eligibility requirements on December 31, 2020.We believe that providing a vehicle for tax-deferred retirement savings though 401(k) Plan and our former simple IRA plan adds to the overall desirability of our executive compensation package and further incentivizes our employees, including our NEOs, in accordance with our compensation policies.
All of our full-time employees, including our NEOs, are eligible to participate in our health and welfare plans, including medical, dental and vision benefits; short-term and long-term disability insurance; and life and AD&D insurance.
Perquisites and Other Personal Benefits
We determine perquisites on a case-by-case basis and will provide a perquisite to an NEO when we believe it is necessary to attract or retain the NEO. In 2021 and 2020, we did not provide any perquisites or personal benefits to our NEOs not otherwise made available to our other employees.
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Outstanding Equity Awards at 2021 Fiscal Year End
The following table lists all outstanding equity awards held by our NEOs as of December 31, 2021.
Option AwardsStock Awards
Name
Vesting
Commencement Date(1)
Number
of
Securities
Underlying Unexercised
Options
Exercisable
(#)
Number
of
Securities
Underlying Unexercised
Options Unexercisable
(#)
Option
Exercise
Price
($)
Option
Expiration
Date
Number
of Shares
that
Have Not
Vested
(#)
Market
Value of
Shares or
Units of
Shares
that Have
Not Vested
($)(2)
Jay R. Venkatesan, M.D.
5/1/2018 (3)
934,400 — 5.89 5/1/2028— — 
6/24/2019 (4)
— — — 6/24/202292,755 268,990 
6/18/2020(1)
46,674 77,792 7.77 6/17/2030— — 
2/5/2021(1)
37,275 141,645 16.00 2/4/2031— — 
Itzhak Goldberg12/19/201840,600 — 6.05 1/21/2029— — 
6/24/2019 (4)
— — — 6/24/202292,755 268,990 
6/18/2020(1)
23,337 38,896 7.77 6/17/2030— — 
2/5/2021(1)
14,585 55,427 16.00 2/4/2031— — 
John Neylan
12/17/2018 (5)
116,687 — 6.43 12/18/2028— — 
6/18/2020(1)
35,005 58,344 7.77 8/30/2030— — 
2/5/2021(1)
14,585 55,427 16.00 12/8/2030— — 

(1)Except as otherwise noted, options and stock awards vest as to 1/48th of the shares subject to the award on each monthly anniversary of the vesting commencement date, subject to the holder's continued service to Angion through each vesting date.
(2)The market value of shares that have not vested is calculated based on the fair market value of our common stock as of December 31, 2021.
(3)The stock option vests as to 25% of the shares on the vesting commencement date and thereafter 10% of the shares vest on each quarterly anniversary, subject to Dr. Venkatesan's continued service to us through such vesting date; provided that an additional 25% of the shares can vest if certain financing goals are achieved.
(4)The non-market performance and service conditions based restricted stock units (PSUs) vest upon the occurrence of two vesting conditions, which must be achieved within seven years from the date of grant, a service vesting condition (the Service-Based Requirement) and a liquidity event requirement (the Liquidity Event Requirement). The Liquidity Event Requirement will be satisfied as to any then-outstanding RSUs that have not terminated earlier on the first to occur of (i) a change in control of Angion or (ii) the six month anniversary of or, if earlier, March 15 of the year following an initial public offering of Angion. The PSUs condition was met upon the closing of our IPO in February 2021. Accordingly, the PSUs vest in three equal parts, with the first part vesting commenced upon the IPO in February 2021, the second part vested on June 24, 2021, and the third part to vest on June 24, 2022. As of December 31, 2021, 371,020 PSUs have been vested.
(5)The stock option shall vest as to 25% of the shares on the first anniversary of the vesting commencement date and vest as to the remaining 75% of the shares in 24 substantially equal monthly installments thereafter, such that all awards will be vested on the third year anniversary of the vesting commencement date, subject to the holder's continued service to Angion through such vesting date.

Executive Compensation Arrangements
We previously entered into offer letter agreements with each of our named executive officers in connection with his or her employment with us. These agreements set forth the terms and conditions of employment of each named executive officer, including initial base salary, equity grants and employee benefits eligibility.
Severance Plan
In connection with our IPO, we entered into new severance and change in control plan that covers all of our NEOs that supersedes and replaces the severance benefits they would otherwise be entitled to receive.
Under our severance plan that encompasses each of our NEOs, if such NEO's employment with us is terminated without "cause" or such NEO resigns for "good reason" (as each is defined in the severance plan), the applicable NEO will be entitled to receive: (i) nine months of continued base salary (or 12 months for Dr. Venkatesan) and (ii) payment or reimbursement of the cost of continued healthcare coverage for nine months (or 12 months for Dr. Venkatesan). In lieu of the foregoing benefits, if each NEO's employment with us is terminated without "cause" or such NEO resigns for "good reason" during the 12-month period following a Change in Control (as defined in the 2021 Plan), the applicable NEO will be entitled to receive: (i) 12 months of continued base salary (or 18 months for Dr. Venkatesan), (ii) payment or reimbursement of the cost of continued healthcare coverage for 12 months (or 18 months for Dr. Venkatesan), (iii) an amount equal to 12 months of such NEO's annual bonus for
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the year of termination assuming 100% of target performance (or 18 months for Dr. Venkatesan) and (iv) full accelerated vesting of any of unvested equity awards (except for any performance awards). The foregoing severance benefits are subject to the applicable NEO's delivery of an executed release of claims against us and continued compliance with the NEO's confidentiality obligations under the severance plan.
Until February 28, 2022, Dr. Goldberg had separate severance arrangements with us set forth in his Employment Agreement with us dated May 1, 2018, providing him severance pay, annual bonus payments and COBRA reimbursements for eighteen (18) months for any termination without “cause”, resignation for “good reason”, or “change of control” as defined by his Employment Agreement. On February 25, 2022, we and Dr. Goldberg entered into a Separation Agreement on such terms.
Director Compensation
We approved a compensation policy for our non-employee directors (Director Compensation Program) that became effective in connection with the consummation of the IPO in February 2021 and is subject to amendment by the board of directors as appropriate. Pursuant to the Director Compensation Program, our non-employee directors receive cash compensation as follows:

Each non-employee director will receive an annual cash retainer in the amount of $40,000 per year.
The Non-Executive Chairperson will receive an additional annual cash retainer in the amount of $35,000 per year.
The lead non-employee director will receive an additional annual cash retained in the amount of $20,000 per year.
The chairperson of the audit committee will receive additional annual cash compensation in the amount of $15,000 per year for such chairperson's service on the audit committee. Each non-chairperson member of the audit committee will receive additional annual cash compensation in the amount of $7,500 per year for such member's service on the audit committee.
The chairperson of the compensation committee will receive additional annual cash compensation in the amount of $10,000 per year for such chairperson's service on the compensation committee. Each non-chairperson member of the compensation committee will receive additional annual cash compensation in the amount of $5,000 per year for such member's service on the compensation committee.
The chairperson of the nominating and corporate governance committee will receive additional annual cash compensation in the amount of $8,000 per year for such chairperson's service on the nominating and corporate governance committee. Each non-chairperson member of the nominating and corporate governance committee will receive additional annual cash compensation in the amount of $5,000 per year for such member's service on the nominating and corporate governance committee.
Under the Director Compensation Program, as amended by the board of directors on March 8, 2021, each non-employee director will automatically be granted an option to purchase 30,000 shares of our common stock upon the director's initial appointment or election to our board of directors (Initial Grant) and an option to purchase 15,000 shares of our common stock automatically on the date of each annual stockholder's meeting thereafter, (Annual Grant), unless otherwise approved by the Board. The Initial Grant will vest as to 1/36th of the underlying shares on a monthly basis over three years, subject to continued service through each applicable vesting date. The Annual Grant will vest on the earlier of the first anniversary of the date of grant or the date of the next annual stockholder's meeting to the extent unvested as of such date, subject to continued service through each applicable vesting date. The exercise price per share of director options is equal to the fair market value of a share of our common stock on the grant date, and the director options will vest in full upon (i) a termination of service due to the director's death or Disability (as defined in the 2021 Plan) and (ii) the consummation of a Change in Control (as defined in the 2021 Plan).
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The following table sets forth information concerning the compensation earned by our non-employee directors during the year ended December 31, 2021.
NameFees Earned or Paid in Cash ($)
Option Awards(1)
($)
Total(2)
 ($)
Victor Ganzi77,500 138,029 215,529 
Allen Nissenson62,500 138,029 200,529 
Gilbert Omenn60,500 138,029 198,529 
Karen Wilson
65,000 138,029 203,029 
__________________________
(1) Amounts shown represents the grant date fair value of options granted during fiscal year 2021 as calculated in accordance with ASC Topic 718. See note 2 of the financial statements included in this Annual Report on Form 10-K for the assumptions used in calculating this amount. As of December 31, 2021, Messrs. Ganzi, Nissenson and Omenn and Ms. Wilson each held options to purchase an aggregate of 53,895 shares of our common stock.
(2) Non-employee directors only received cash fees and stock awards as compensation for their service on the Board of Directors.
The Compensation Committee of the Board has reviewed and assessed Angion’s compensation policies and practices as they related to risk management are not reasonably likely to have a material adverse effect on Angion.10-K.

Item 12. Security ownership of certain beneficial owners and management and related stockholder matters.
The following table sets forth certain information regardingrequired by this Item is incorporated herein by reference to the beneficial ownershipinformation that will be contained in our proxy statement related to the 2024 Annual Meeting of our common stock asStockholders, which we intend to file with the Securities and Exchange Commission within 120 days of March 1, 2022 by:the end of the fiscal year covered by this Annual Report on Form 10-K pursuant to General Instruction G(3) of Form 10-K.

each person, or group of affiliated persons, known by us to beneficially own more than 5% of our outstanding shares of our common stock;
each of our directors;
each of our named executive officers; and
all directors and executive officers as a group.Item 11. Executive Compensation
The numberinformation required by this Item is incorporated herein by reference to the information that will be contained in our proxy statement related to the 2024 Annual Meeting of shares beneficially owned by each entity, person, director or executive officer is determined in accordanceStockholders, which we intend to file with the rulesSecurities and Exchange Commission within 120 days of the SEC, and the information is not necessarily indicative of beneficial ownership for any other purpose. Under such rules, beneficial ownership includes any shares over which the individual has sole or shared voting power or investment power as well as any shares that the individual has the right to acquire within 60 days after March 1, 2022 through the exercise of any stock option, warrants or other rights. Except as otherwise indicated, and subject to applicable community property laws, the persons named in the table have sole voting and investment power with respect to all shares of our common stock held by that person.

The percentage of shares beneficially owned is computed on the basis of 29,957,509 shares of our common stock outstanding as of March 1, 2022. Shares of our common stock that a person has the right to acquire within 60 days after March 1, 2022 are deemed outstanding for purposes of computing the percentage ownership of the person holding such rights, but are not deemed outstanding for purposes of computing the percentage ownership of any other person, except with respect to the percentage ownership of all directors and executive officers as a group.

Unless otherwise indicated below, the address for each beneficial owner listed is c/o Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, New York 11553.

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Beneficiary Ownership Table
as of March 1, 2022
NumberPercentage
5% and Greater Stockholders:
Jay R. Venkatesan (1)
2,880,8989.2 %
Itzhak D. Goldberg (2)
1,995,1216.6 %
Vifor International, Ltd1,995,6436.7 %
EISA-ABC, LLC (3)
1,722,2375.7 %
Named Executive Officers and Directors:
Jay R. Venkatesan (4)
2,880,8989.2 %
Itzhak D. Goldberg (5)
1,995,1216.6 %
Victor F. Ganzi (6)
1,019,6283.4 %
John Neylan(7)
257,567*
Gilbert S. Omenn (8)
121,256*
Allen R. Nissenson (9)
40,930*
Karen J. Wilson (10)
59,648*
All directors and executive officers as a group (9 persons) (11)
6,671,97820.8 %

*     Represents beneficial ownership of less than 1% of the shares of our common stock.
(1)     Consists of (i) 1,639,257 shares of our common stock held directly by Jay R. Venkatesan and (ii) 1,241,641 shares of our common stock that may be acquired pursuant to the exercise of stock options within 60 days of March 1, 2022.
(2)    Consists of (i) 1,720,068 shares of our common stock held directly by Dr. Goldberg; (ii) 233,374 shares of our common stock held by Itzhak D. Goldberg's Grandchildren's Trust #1 and 116,687 shares of our common stock held by the Itzhak D. Goldberg's Grandchildren's Trust #2, both in which Dr. Goldberg disclaims any pecuniary interest and (iii) 273,053 shares of our common stock that may be acquired pursuant to the exercise of stock options within 60 days of March 1, 2022.
(3)    Based on a Schedule 13G filed on February 14, 2022. The address of EISA-ABC, LLC is 41 Brayton Street, Englewood, NJ 07631.
(4)     Consists of the shares described in footnote 1 above.
(5)     Consists of the shares described in footnote 2 above.
(6)     Consists of (i) 823,117 shares of our common stock held directly by Victor F. Ganzi and 155,581 shares of our common stock held by Victor F Ganzi 2012 GST Family Trust held by Victor Ganzi; (ii) 40,930 shares of our common stock that may be acquired pursuant to the exercise of stock options within 60 days of March 1, 2022.
(7)     Consists of (i) 35,136 shares of our common stock held directly by John Neylan and (ii)222,431 shares of our common stock that may be acquired pursuant to the exercise of stock options within 60 days of March 1, 2022.
(8)     Consists of (i) 80,326 shares of our common stock held by the Gilbert S. Omenn Revocable Trust and (ii) 40,930 shares of common stock that may be acquired pursuant to the exercise of stock options within 60 days of March 1, 2022.
(9)     Consists of 40,930 shares of our common stock that may be acquired pursuant to the exercise of stock options within 60 days of March 1, 2022.
(10)     Consists of (i)18,718 shares of our common stock held directly by Karen Wilson and (ii) 40,930 shares of our common stock that may be acquired pursuant to the exercise of stock options within 60 days of March 1, 2022.
(11)     Consists of (i) the shares described in footnotes 3 through 9 above, (ii) 34,399 shares of our common stock held by two other executive officers who are not in the table above, and (iii) 262,531 shares of our common stock that may be acquired pursuant to the exercise of stock options held by the two other executive officers who are not in the table above within 60 days of March 1, 2022.

Equity Compensation Plan Information

The following table summarizes our equity compensation plan information as of December 31, 2021. Information is included for equity compensation plans approved by our stockholders. As of December 31, 2021, we did not have any equity compensation plans that were not approved by our stockholders.

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Name
Number of
Securities to
be Issued
Upon Exercise
of Outstanding
Options,
Warrants
and Rights(1)
Weighted
Average
Exercise
Price of
Outstanding
Options,
Warrants
and Rights(2)
Number of
Securities
Remaining
Available for
Future
Issuance
Under Equity
Compensation
Plans
Equity compensation plans approved by stockholders4,433,177 $8.51 4,168,609 
Equity compensation plans not approved by stockholders— — — 
Total4,433,177 $8.51 4,168,609 
(1) Consists of shares subject to our 2015 Equity Incentive Plan (the “2015 Plan”), our 2021 Incentive Award Plan. (the “2021 Plan”), and 2021 Employee Stock Purchase Plan (the “ESPP”). The 2021 Plan contains an “evergreen” provision, pursuant to which the number of shares of common stock reserved for issuance pursuant to awards under such plan shall be increased on the first day of each year equal to the lesser of (i) 5% of the number of shares of common stock outstanding (on an as converted basis) on the last day of the immediately preceding fiscal year, or (ii) if our Board acts prior to the first dayend of the fiscal year such lesser amount that our Board determines for purposes of the annual increase of the fiscal year. As of January 1, 2022, the 2021 Plan was increasedcovered by 1,497,818this Annual Report on Form 10-K pursuant to such evergreen provision. The ESPP contains an “evergreen” provision, pursuant to which the numberGeneral Instruction G(3) of shares of common stock reserved for issuance pursuant to awards under such plan shall be increased on the first day of each year equal to the lesser of (i) 299,564 (on an as converted basis) on the last day of the immediately preceding fiscal year, or (ii) if our Board acts prior to the first day of the fiscal year, such lesser amount that our Board determines for purposes of the annual increase of the fiscal year. As of January 1, 2022, the ESPP was increased by 1% of share outstanding shares as of January 1, 2022 pursuant to such evergreen provision. No shares are reflected as being subject to rights as of December 31, 2021 as we have not started any offering periods under the ESPP and, even if we did, such number of shares could not be calculated.
(2) Shares subject to RSUs and PSUs do not have an exercise price. The weighted average exercise price for just the stock options outstanding was $8.92.Form 10-K.


Item 13. Certain Relationships and Related Transactions, and Director Independence
The followinginformation required by this Item is a description of transactions since January 1, 2020 to which we have been a party, in which the amount involved exceeds or will exceed $120,000, and in which any of our directors, executive officers or beneficial owners of more than 5% of our capital stock, or an affiliate or immediate family member thereof, had or will have a direct or indirect material interest, other than compensation, termination and change-in-control arrangements, which are described under "Executive Compensation." We also describe below certain other transactions with our directors, executive officers and stockholders.
All of the transactions set forth below were approvedincorporated herein by a majority of our board of directors. We believe that we have executed all of the transactions set forth below on terms no less favorable to us than we could have obtained from unaffiliated third parties. It is our intention to ensure that all future transactions between us and our officers, directors and principal stockholders and their affiliates are approved by our audit committee, once it is constituted, and a majority of the members of our board of directors, including a majority of the independent and disinterested members of our board of directors, and are on terms no less favorable to us than those that we could obtain from unaffiliated third parties.
Convertible Note Financings
All of our issued convertible promissory notes were converted to common stock in February 2021 upon our IPO. During 2020, $1.8 million convertible notes from Dr. Venkatesan were exchanged into convertible preferred stock in August 2020 which were then converted into common stock upon IPO.
In the first nine months of 2020, we issued convertible promissory notes (the Convertible Notes) to certain investors in aggregate principal amount of $34.8 million. The Convertible Notes accrued interest at a rate of 12% per annum, and convert into shares of our common stock upon the consummation of our IPO. In December 2020, we issued Vifor Pharma a convertible promissory note in aggregate principal amount of $5.0 million as part of the equity investment with a maturity date of three years, 2% interest and a conversion price of $11.57 per share, which was automatically converted into shares of our common stock upon our IPO.
The table below sets forth the principal amount, and number of shares of issuable upon conversion of the Convertible Notes issued in 2020 to our directors, executive officers or owners of more than 5% of a class of our
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capital stock, or an affiliate or immediate family member thereof:
NameConvertible Note Issued and Outstanding as of December 31, 2020 ( Principal Amount)
Number of
Shares of Our
Common Stock
Issuable Upon
Conversion(2)
Gilbert S. Omenn, M.D., Ph.D.(2)
$661,540 61,657
Jay R. Venkatesan, M.D.(3)(4)
$2,965 262
Victor F. Ganzi(3)(5)
$747,671 68,863
Karen Wilson(6)
$200,000 18,718
Vifor (International) Ltd.(7)
$5,000,000 433,143

(1)The terms of the Convertible Notes provide that the notes and accrued dividends will convert at a price that is equal to a 20% discountreference to the price of the common stock offeredinformation that will be contained in our IPO. The number of shares reflected are based on an initial public offering price of $16.00 per share and assumed the conversion occurs on February 9, 2021.
(2)Dr. Omenn is a member of our board of directors. Amount shown includes Convertible Notes held by the Gilbert S. Omenn Revocable Trust, an estate planning instrument for which Mr. Omenn is trustee.
(3)Consists of common stock converted from both convertible notes outstanding and convertible preferred stock outstanding.
(4)Dr. Venkatesan is our chief executive officer and a member of our board of directors.
(5)Mr. Ganzi is a member of our board of directors.
(6)Ms. Wilson is a member of our board of directors.
(7)Vifor (International) Ltd. is our licensing partner.
Transactions with NovaPark LLC
We rent office and laboratory space in Uniondale, New York from NovaPark LLC (NovaPark), an affiliated company, under a lease that expires on June 20, 2026. The space that we rent is part of a 110,000-square-foot general laboratory and development facility (the NovaPark Facility) for biological and chemistry research owned by NovaPark. We recorded rent expense for fixed lease payments of $1.1 million and $1.0 million for years ended December 31, 2021 and 2020, respectively. We recorded rent expense for variable expensesproxy statement related to the lease2024 Annual Meeting of $0.5 millionStockholders, which we intend to file with the Securities and $0.6 million for the years ended December 31, 2021 and 2020.
We, Dr. Goldberg and Rina Kurz, Dr. Goldberg's spouse, own 10%, 45% and 45%, respectively,Exchange Commission within 120 days of the membership interests in NovaPark LLC.
The NovaPark Facility has been financedend of the fiscal year covered by a mortgagethis Annual Report on Form 10-K pursuant to which NovaPark's payment obligations are guaranteed by Dr. Goldberg, including a limited personal guarantee up to an amountGeneral Instruction G(3) of $2.1 million. In 2016, in connection with the refinancing of the mortgage, we entered into an indemnification agreement with Dr. Goldberg, pursuant to which we agreed to indemnify Dr. Goldberg from any loss arising out of any claim or action asserted by the mortgage lender against Dr. Goldberg related to Dr. Goldberg's personal limited guarantee of the mortgage. In February 2020, we and Dr. Goldberg terminated the indemnification agreement.
Consultant Fees and Employment of Immediate Family
We have paid consulting fees under an agreement with Rina Kurz, Dr. Goldberg's spouse, for management and administrative services relating to our U.S. government grants and contracts. For the year ended December 31, 2021, consultant fees paid to Ms. Kurz were approximately $0.1 million. We believe the consulting arrangement with Ms. Kurz was made on terms no less favorable to us than those that we could obtain from unaffiliated third parties. Angion terminated Ms. Kurz’s consultant agreement in February 2022.
Elisha Goldberg, Dr. Goldberg's son, who formerly served as our Vice President and Director of Strategy, was separated from his employment with us on January 31, 2022 as part of our reduction in force announced in January 2022.For the year ended December 31, 2021, Elisha Goldberg was paid $0.3 million in salary and total award of options during 2021 representing less than 0.1% of our fully diluted capitalization.
Policies and Procedures for Related Party Transactions
Our board of directors has adopted a related party transaction policy setting forth the policies and procedures for the identification, review and approval or ratification of related party transactions. This policy covers, with certain exceptions set forth in Item 404 of Regulation S-K under the Securities Act, any transaction, arrangement or
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relationship, or any series of similar transactions, arrangements or relationships, in which we and a related party were or will be participants and the amount involved exceeds $120,000, including purchases of goods or services by or from the related party or entities in which the related party has a material interest, indebtedness and guarantees of indebtedness. In reviewing and approving any such transactions, our audit committee will consider all relevant facts and circumstances as appropriate, such as the purpose of the transaction, the availability of other sources of comparable products or services, whether the transaction is on terms comparable to those that could be obtained in an arm's length transaction, management's recommendation with respect to the proposed related party transaction, and the extent of the related party's interest in the transaction.
Director Independence
Our board of directors currently consists of six members. Our board of directors has determined that all of our directors, other than Dr. Venkatesan and Dr. Goldberg, qualify as "independent" directors in accordance with The Nasdaq Stock Market listing requirements. Dr. Venkatesan and Dr. Goldberg are not considered independent because they were employees of Angion Biomedica Corp. in 2021. As of March 2022, Dr. Goldberg was no longer an employee of Angion. In addition, as required by The Nasdaq Stock Market rules, our board of directors has made a subjective determination as to each independent director that no relationships exist that, in the opinion of our board of directors, would interfere with the exercise of independent judgment in carrying out the responsibilities of a director. In making these determinations, our board of directors reviewed and discussed information provided by the directors and us with regard to each director's business and personal activities and relationships as they may relate to us and our management. There are no family relationships among any of our directors or executive officers.Form 10-K.

Item 14. Principal Accountant Fees
The following table sets forth all fees billed for professional audit, taxinformation required by this Item is incorporated herein by reference to the information that will be contained in our proxy statement related to the 2024 Annual Meeting of Stockholders, which we intend to file with the Securities and other services renderedExchange Commission within 120 days of the end of the fiscal year covered by Moss Adams LLP (in thousands):
Year Ended December 31,
20212020
Audit Fees (1)
$408 $979 
Tax Fees (2)
2214
Other (3)
31 35 
Total Fees$461 $1,028 
__________________________
(1) Audit fees are for professional services for the auditthis Annual Report on Form 10-K pursuant to General Instruction G(3) of our financial statements, the review of quarterly interim financial statements, and for services that are normally provided by the accountant in connection with other regulatory filings or engagements. Fees for the year ended December 31, 2021 include services associated with our IPO and services rendered for the 2021 audit. Fees for the year ended December 31, 2020 include services associated with our IPO.
(2) Tax fees are for compliance and consultation.
(3) Other fees are for grant compliance audit fee in 2021 and 2020.Form 10-K.
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Part IV
Item 15. Exhibits and Financial Statement Schedules
(a)Financial Statements: See “Index to Consolidated Financial Statements” in Part II, Item 8 of this Annual Report on Form 10-K
(b)Exhibits.
Exhibit
Number
Exhibit
Description
Incorporated by
Reference
Filed Herewith
FormDateNumber
3.18-K2/9/20213.1
3.28-K2/9/20213.2
4.1Reference is made to exhibits 3.1 through 3.2.
4.2S-1/A2/1/20214.2
4.3S-11/15/20214.3
4.4S-11/15/20214.6
4.5X
10.1S-11/15/202110.1
10.2†S-11/15/202110.4
10.2(a)†X
10.3(a)#S-11/15/202110.5(a)
10.3(b)#S-11/15/202110.5(b)
10.3(c)#S-11/15/202110.5(c)
10.3(d)#S-11/15/202110.5(d)
10.4(a)#S-1/A2/1/2021 10.6(a)
10.4(b)#S-1/A2/1/202110.6(b)
10.4(c)#S-1/A2/1/202110.6(c)
10.4(d)#S-1/A2/1/202110.6(d)
10.5#S-1/A2/1/202110.7
10.6#S-11/15/202110.8
10.7#S-11/15/202110.9
10.7(a)X
10.8(b)X
10.9#S-11/15/202110.10
10.10#S-11/15/202110.11

Exhibit
Number
Exhibit
Description
Incorporated by
Reference
Filed Herewith
FormDateNumber
2.18-K1/17/20232.1
3.18-K2/9/20213.1
3.28-K6/2/20233.3
3.38-K6/2/20233.4
3.48-K6/2/20233.5
3.58-K2/9/20213.2
4.1Reference is made to exhibits 3.1 through 3.5.
4.2S-1/A2/1/20214.2
4.3S-11/15/20214.3
4.4S-11/15/20214.6
4.510-K3/30/20224.5
10.1S-4/A3/29/202310.34
10.2#

8-K6/2/202310.2+
10.3

8-K6/2/202310.8
10.4

8-K6/2/202310.13
10.5#S-4/A3/29/202310.29+
10.6#S-4/A3/29/202310.30+
10.7#
10.8#

S-4/A3/29/202310.32+
10.98-K12/22/202310.1
10.10#S-4/A3/29/202310.27+
10.11#

S-4/A3/29/202310.28+
10.12†

S-4/A3/29/202310.25+
10.138-K1/17/202310.1
10.14#X
10.15#8-K2/2/202410.1
10.16(a)#S-11/15/202110.5(a)
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Table of Contents
Exhibit
Number
Exhibit
Description
Incorporated by
Reference
Filed Herewith
FormDateNumber
10.11#S-11/15/202110.12
10.11(a)#X
10.11(b)#X
10.11(c)#X
10.12#X
10.13S-11/15/202110.14
10.14#X
10.15#X
20158-K2/09/202110.1
2016#8-K3/04/2022Item 5.02
21.1S-11/15/202121.1
23.1X
24.1X
31.1X
31.2X
32.1^X
32.2^X
10.16(b)#S-11/15/202110.5(b)
10.16(c)#S-11/15/202110.5(c)
10.16(d)#S-11/15/202110.5(d)
10.17(a)#S-1/A2/1/202110.6(a)
10.17(b)#

S-1/A2/1/202110.6(b)
10.17(c)#S-1/A2/1/202110.6(c)
10.17(d)#S-1/A2/1/202110.6(d)
10.18#S-1/A2/1/202110.7
10.19#X
10.20#X
10.21#X
21.1S-11/15/202121.1
23.1X
24.1X
31.1X
31.2X
32.1^X
32.2^X
97.1
101.INSInline XBRL Instance DocumentX
101.SCHInline XBRL Taxonomy Extension Schema DocumentX
101.CALInline XBRL Taxonomy Extension Calculation Linkbase DocumentX
101.DEFInline XBRL Taxonomy Extension Definition Linkbase DocumentX
101.LABInline XBRL Taxonomy Extension Label Linkbase DocumentX
101.PREInline XBRL Taxonomy Extension Presentation Linkbase DocumentX
104Cover Page Interactive Data FileX

Portions of this exhibit have been omitted in accordance with Item 601(b)(10) of Regulation S-K.
#Indicates management contract or compensatory plan.
^The certification that accompanies thisthe Annual Report on Form 10-K pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, is not deemed “filed” by the Registrant for purposes of Section 18 of the Securities Exchange Act of 1934, as amended.



Item 16. Form 10-K Summary
Not applicable.
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SIGNATURES

Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
ANGION BIOMEDICA CORP.
By:/s/ JAY R. VENKATESAN, M.D.
Jay R. Venkatesan, M.D.
President and Chief Executive Officer and Chairman

Date: March 29, 2024


ELICIO THERAPEUTICS, INC.

By: /s/ Robert Connelly
Robert Connelly
Chief Executive Officer


Power of Attorney
KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below hereby constitutes and appoints Jay R. Venkatesan, M.D.Robert Connelly and Jennifer J. Rhodes,Brian Piekos, and each of them acting individually, as his or her true and lawful attorneys-in-fact and agents, each with full power of substitution, for him or her in any and all capacities, to sign any and all amendments to this Registration StatementAnnual Report on Form 10-K and to file the same, with all exhibits thereto and other documents in connection therewith, with the SEC, granting unto said attorneys-in-fact and agents, with full power of each to act alone, full power and authority to do and perform each and every act and thing requisite and necessary to be done in connection therewith, as fully for all intents and purposes as he might or could do in person, hereby ratifying and confirming all that said attorneys-in-fact and agents, or his or their substitute or substitutes, may lawfully do or cause to be done by virtue hereof.

Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, this Registration Statementreport has been signed by the following persons in the capacities and on the dates indicated.

SignatureTitleDate
SignatureTitleDate
/s/ JAY R. VENKATESAN, M.D.Robert Connelly
Robert Connelly
President and Chief Executive Officer, President and Chairman of the Board (PrincipalDirectorMarch 29, 2024
(Principal Executive Officer)
/s/ Brian PiekosChief Financial OfficerMarch 30, 202229, 2024
Brian Piekos(Principal Financial Officer and Principal Accounting Officer)
/s/ Jay Venkatesan, M.D.DirectorMarch 29, 2024
Jay R. Venkatesan, M.D.
/s/ GREGORY S. CURHANJulian Adams, Ph.D.DirectorChief Financial Officer (Principal Financial and Accounting Officer)March 30, 202229, 2024
Gregory S. CurhanJulian Adams, Ph.D.
/s/ ITZHAK D. GOLDBERG,Carol AsheDirectorMarch 29, 2024
Carol Ashe
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/s/ Yekaterina (Katie) ChudnovskyDirectorMarch 29, 2024
Yekaterina (Katie) Chudnovsky
/s/ Robert R. Ruffolo, Jr., Ph.D.DirectorMarch 29, 2024
Robert R. Ruffolo, Jr., Ph.D.
/s/ Karen WilsonDirectorMarch 29, 2024
Karen Wilson
/s/ Allen Nissenson, M.D.DirectorDirector and Chairman EmeritusMarch 30, 2022
Itzhak D. Goldberg, M.D.
/s/ VICTOR F. GANZI29, 2024
Lead Independent Director

March 30, 2022
Victor F. Ganzi
/s/ ALLEN R. NISSENSON, M.D.DirectorMarch 30, 2022
Allen R. Nissenson, M.D.
/s/ GILBERT S. OMENN, M.D., PH.D.DirectorMarch 30, 2022
Gilbert S. Omenn, M.D., Ph.D.
/s/ KAREN J. WILSONDirectorMarch 30, 2022
Karen J. Wilson

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