UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, DC 20549
FORM 10‑K10-K
(Mark One) | |
☒ | ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 |
For the fiscal year ended December 31, | |
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: 001‑36182001-36182
Xencor, Inc.Inc.
(Exact Name of Registrant as Specified in its Charter)
Delaware |
|
111 West Lemon Avenue, Monrovia, CA | 91016 |
(626) 305‑5900(626) 305-5900
(Registrant’s Telephone Number, Including Area Code)
Securities registered pursuant to Section 12(b) of the Act:
Title of | Trading Symbol | Name of | ||
Common Stock, par value $0.01 per share | | XNCR | | The |
Securities registered pursuant to Section 12(g) of the Act: None
Indicate by check mark if the registrant is a well‑knownwell-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 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‑TS-T (§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 if disclosure of delinquent filers pursuant to Item 405 of Regulation S‑K is not contained herein, and will not be contained, to the best of the registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10‑K or any amendment to this Form 10‑K. ☐
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 filer ☒ | Accelerated filer ☐ | Non-accelerated filer ☐ | Smaller 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. ☒
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b‑212b-2 of the Securities Exchange Act of 1934). Yes ☐ No ☒
The aggregate market value of the voting and non-voting common equity held by non-affiliates computed by reference to the price at which the common equity was last sold as of June 30, 20182020 was $2,046,791,343$1,843,897,240.
The number of outstanding shares of the registrant’s common stock, par value $0.01 per share, as of February 15, 201916, 2021 was 56,292,169.57,945,225.
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the registrant’s proxy statement to be filed with the Securities and Exchange Commission pursuant to Regulation 14A in connection with the registrant’s 20192021 Annual Meeting of Stockholders, which will be filed subsequent to the date hereof, are incorporated by reference into Part III of this Form 10‑K.10-K. Such proxy statement will be filed with the Securities and Exchange Commission not later than 120 days following the end of the registrant’s fiscal year ended December 31, 2018.2020.
Xencor, Inc.
FORM 10‑K10-K
For the Fiscal Year Ended December 31, 20182020
| | Page | ||
| | | | |
| ||||
| | 26 | ||
| | 52 | ||
| | 52 | ||
| | 52 | ||
| | 52 | ||
| | | | |
| | 52 | ||
| | 54 | ||
| Management’s Discussion and Analysis of Financial Condition and Results of Operations | | 55 | |
| | 75 | ||
| | 75 | ||
| Changes in and Disagreements With Accountants on Accounting and Financial Disclosure | |||
112 | ||||
| | 112 | ||
| | 113 | ||
| | | | |
| | 114 | ||
| | 114 | ||
| Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters | | 114 | |
| Certain Relationships and Related Transactions, and Director Independence | | 114 | |
| ||||
114 | ||||
| | | | |
| | 115 | ||
| | 118 | ||
| | | 119 |
The Xencor logo is a trademark of Xencor, Inc. XmAb, PDA and Protein Design Automation are also registered trademarks of Xencor. All other product and company names are trademarks of their respective companies. References in this Annual Report on Form 10-K to “we”, “our”, “us”, “Xencor” or “the Company” refer to Xencor, Inc.
2
PART I
Forward‑LookingForward-Looking Statements
This Annual Report on Form 10‑K or this Annual Report, may contain “forward‑looking statements”10-K contains forward-looking statements within the meaning of the federal securities laws made pursuant to the safe harbor provisionsSection 27A of the Private Securities Litigation Reform Act of 1995.1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. You should not place undue reliance on these statements. We have based these forward‑lookingforward-looking statements largely on our current expectations and projections about future events and financial trends affecting the financial condition of our business. Forward‑lookingForward-looking statements should not be read as a guarantee of future performance or results and will not necessarily be accurate indications of the times at, or by, which such performance or results will be achieved. Forward‑lookingForward-looking statements are based on information available at the time those statements are made and/or management’s good faith belief as of that time with respect to future events, and are subject to risks and uncertainties that could cause actual performance or results to differ materially from those expressed in or suggested by the forward‑lookingforward-looking statements. Our actual results could differ materially from those anticipated in these forward‑lookingforward-looking statements as a result of various factors, including those set forth below under Part I, Item 1A, “Risk Factors” in this Annual Report. These statements, which represent our current expectations or beliefs concerning various future events, may contain words such as “may,” “will,” “expect,” “anticipate,” “intend,” “plan,” “believe,” “estimate” or other words indicating future results. Such statements may include, but are not limited to, statements concerning the following:
| the |
| ● | our ability to execute on our plans to research, develop and |
| ● | the success of our ongoing and |
| the timing of and our ability to obtain and maintain regulatory approval |
| our ability to |
| ● | our ability to receive research funding |
| our |
|
|
| our ability to attract collaborators with development, regulatory, and commercialization expertise; |
| our ability to |
|
|
|
|
| the rate and degree of market acceptance and clinical utility of our |
| costs of compliance and our |
|
|
|
|
|
|
| the potential loss or retirement of key |
| our failure to successfully execute our growth strategy including any delays in our planned future growth; |
3
| our failure to maintain effective internal controls; and |
3
|
|
Given these uncertainties, you should not place undue reliance on these forward‑lookingforward-looking statements. These forward‑lookingforward-looking statements represent our estimates and assumptions only as of the date of this Annual Report, on Form 10‑K and except as required by law, we undertake no obligation to update or revise publicly any forward‑lookingforward-looking statements, whether as a result of new information, future events, or otherwise after the date of this Annual Report on Form 10‑K.Report. We qualify all of our forward‑lookingforward-looking statements by these cautionary statements.
Our Business
We are a clinical‑stageclinical-stage biopharmaceutical company focused on discovering and developing engineered monoclonal antibody and other proteincytokine therapeutics to treat severepatients with cancer and life‑threateningautoimmune diseases withwho have unmet medical needs. We are developingadvancing a suitebroad portfolio of clinical-stage drug candidates from our proprietary XmAb® technology platforms that are designedplatforms. We use our protein engineering capabilities to treat cancer, autoimmuneincrease our understanding of protein structure and allergic diseases,interactions and other conditions.to design new XmAb technologies and development candidates with improved properties. In contrast to conventional approaches to antibody design, which focus on the portionsegment of antibodies that interact with target antigens, our protein engineering efforts and the XmAb technologies arework is focused on the portionFc domain, the part of thean antibody that interacts with multiple segments of the immune system and controls antibody structure. This portion, referred to as theThe Fc domain is constant and interchangeable among antibodies. Ourantibodies, and our engineered Fc domains, the XmAb technology, can be readily substituted for natural Fc domains.
We believeOur protein engineering capabilities and XmAb technologies enable us and our Fc domainspartners to develop antibodies and biotherapeutic drug candidates with improved properties and function, which can provide innovative approaches to treating disease and potential clinical advantage over other treatment options. For example, our capabilities have enabled us to develop an antibody scaffold to rapidly create novel bispecific antibodies that bind two different targets simultaneously, creating entirely new biological mechanisms. Other applications of our XmAb technologies enhance antibody performance by for example, increasing immune inhibitory activity, improving cytotoxicity, extending circulating half‑life, orhalf-life and stabilizing novel antibody and other protein structures, while maintaining 99.5% identitysuch as engineered cytokines. Currently, there are two marketed drugs that have been developed with our XmAb technologies.
On July 31, 2020, the U.S. Food and Drug Administration (FDA) approved our partner MorphoSys’ Monjuvi® (tafasitamab-cxix) in structurecombination with lenalidomide, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and sequencewho are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). We created and initially developed tafasitamab, which incorporates our XmAb Cytotoxic Fc Domain to natural antibodies. By designing antibodies and other protein molecules with improved function, we believe that our XmAb‑engineered proteins offer innovative approaches to treating disease and potential clinical advantages over other treatments. In December 2018, theenhance its tumor killing properties. Monjuvi is a registered trademark of MorphoSys AG.
Alexion's Ultomiris® (ravulizumab-cwvz) was first antibody that incorporates an XmAb technology, ALXN1210, now Ultomiris™, was approved by the United States Food & Drug Administration (FDA) for commercial marketing. Ultomiris™FDA in December 2018. It is a complement inhibitor indicatednow approved in the U.S., Europe and Japan for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) that was developed byand for the treatment of patients with atypical hemolytic uremic syndrome (aHUS). Alexion used our partner Alexion, and incorporates our XtendXtend™ Fc technology which allowsDomain to enhance the half-life of Ultomiris to allow for a longer duration of action, and less frequent dosing regimensand reduced patient burden of therapy compared to the previously approvedprevious generation therapy, Soliris®.
Our protein engineering capabilities allow us to continually explore new functionality in the Fc region, which provides us with opportunities to:
|
|
|
|
4
| Provide collaboration and licensing opportunities with partners for application of our technologies, access to our technologies, access to our drug candidates, or combinations of each. |
Our Strategy
Our goal is to become a leading biopharmaceutical company focused on developing and commercializing engineered biologic medicines to treat patients with severe and life-threatening diseases with unmet medical needs. Key elements of our strategy are to:
| 1. | Advance the clinical development of our XmAb bispecific antibody and cytokine drug candidates. Our modular XmAb bispecific technology and protein engineering capabilities enable us to rapidly advance multiple drug candidates into clinical development. We and our partners are enrolling Phase 1 studies for seven of these candidates to treat patients with many different types of cancer, and an eighth, to be developed for patients with autoimmune disease, is expected to start a Phase 1 study in early 2021. We and our partners plan to advance additional bispecific antibodies and cytokines into clinical development in the future. |
| 2. | Build a large and diversified portfolio of XmAb drug candidates. We create new XmAb-engineered antibody and cytokine product candidates to exploit the novel mechanisms of action enabled by our XmAb technology platforms and advance them into our internal portfolio of preclinical and clinical-stage assets, or, if strategically appropriate, we license certain drug candidates to leading pharmaceutical and biotechnology companies. |
| 3. | Leverage our protein engineering capabilities, XmAb technologies, and XmAb drug candidates with partnerships, collaborations, and licenses to generate revenue streams, create new drug candidates and combination treatments, and identify new indications for our pipeline of Generate revenue streams. The plug-and-play nature of our XmAb technologies and our ability to generate multiple drug candidates efficiently provides us opportunities to generate revenue from licensing and collaboration arrangements. In 2020, we received total proceeds of $165 million in upfront payments, milestone payments and royalties from such arrangements. Create new drug candidates and investigate novel combination therapies. We seek to leverage our XmAb technologies and drug candidates with partners to create novel drug candidates, including combination therapies. In 2020, we entered into separate agreements with Atreca, Inc. and The University of Texas MD Anderson Cancer Center to create novel CD3 bispecific antibody drug candidates. We also entered into a clinical collaboration with MorphoSys AG and Incyte Corporation, in which we plan to conduct multiple clinical studies in B-cell lymphomas, combining our plamotamab drug candidate with tafasitamab in combination with lenalidomide. Identify new indications for our pipeline of drug candidates.In August 2020, we entered into a five-year strategic collaboration with MD Anderson. We will support Investigator Sponsored Trials (ISTs) in which MD Anderson's investigators may explore additional indications for our pipeline of candidates. |
| 4. | Broaden the functionality of our XmAb technology platform. We are conducting further research into the function and application of antibody Fc domains in order to expand the scope of our XmAb technology platforms. We use the modularity of our XmAb bispecific Fc technology to build bispecific antibodies and cytokines in a variety of formats, recently introducing CD3 bispecific antibodies of a mixed valency format, the XmAb 2+1 bispecific antibody. XmAb 2+1 bispecific antibodies may preferentially kill tumor cells with high target expression which may be especially beneficial in designing antibodies that target solid tumors. Additionally, we have engineered CD28 bispecific antibodies to provide conditional CD28 co-stimulation of T cells, activating them when bound to tumor cells. Targeted CD28 bispecific antibodies may provide conditional co-stimulation of T cells, for example, to T cells recognizing neoantigens or in concert with CD3 T-cell engaging bispecific antibodies. |
The most recent expansion of our platform is the XmAb bispecific Fc domains, which enable the rapid design and simplified development of antibodies and other protein structures that bind two or more different targets simultaneously. Bispecifics are a rapidly emerging area of biotherapeutics development, particularly in oncology, and we are using our XmAb bispecific Fc domains as a robust scaffold to develop a pipeline of new bispecific antibody and cytokine drug candidates.
45
| 5. | Continue to expand our patent portfolio protecting our XmAb technologies and XmAb candidates. We seek to expand our intellectual property estate and protect our XmAb technologies, our development programs, and product candidates by filing and prosecuting patents in the United States and other countries. Where appropriate we will seek expansion and extension of patents issued for our product candidates. |
Our business strategy is to leverage our bispecific Fc technology and Fc engineering capabilities to develop and advance a pipeline of oncology candidates. We believe that bispecific technologies and candidates will play a growing role in the field of oncology, and that our Fc capabilities and technologies position us to be a leader in this field. We will also continue to leverage our other XmAb drug candidates and Fc technologies through partnerships and collaborations.
Since we began focusing our efforts in the bispecific field, we have advanced seven bispecific Fc candidates into development, expanded the functionality of the bispecific Fc technology, and entered into three collaborations with major pharmaceutical companies that will generate over $300 million in upfront payments. These collaborations provide us opportunities to co-develop drug candidates to leverage our partners’ capabilities and also to potentially earn substantial future revenue from potential milestones, royalties, and profit-sharing rights.
XmAb Bispecific Fc TechnologyTechnologies
A distinguishing feature of our XmAb technologies isarises from our modular approach to Fcprotein engineering. This provides us with flexibility to seek out new functionality inapplications of the bispecificXmAb Bispecific Fc domain, allowsDomain and enables us to design new bispecific antibody and cytokine drug candidates with distinct and novel mechanisms-of-action, and also allows for different variable target combinations.mechanisms-of-action. This approach is illustrated through ourthe expansion of our portfolio of novel bispecific Fc platformantibody and the novel candidates that we have designed.cytokine candidates. Our business, research, and clinical efforts are to develop and advance our XmAb bispecific technologies and our portfolio of bispecific antibodies and cytokines in oncology and autoimmune diseases.
CD3 bispecific candidates: the our initial bispecific antibody candidates that weare designed were created with our engineered heterodimer Fc domain, or bispecific Fc domain,to redirect T cells to tumor cells through the engagement of an antigen on tumor cells and are dual-antigen targeting molecules, containing an anti-tumor associated antigen binding domain and a second binding domain targeted to CD3, an activating receptor on T-cells. The goal of the “CD3 bispecific” is to recruit or activate T-cells against the antigen target.T cells. We are advancingcurrently conducting Phase 1 studies for three CD3 bispecific antibody candidates: plamotamab, vibecotamab, and tidutamab.
We have expanded our T-cell redirecting CD3 class of bispecific antibodies to create the XmAb 2+1 bispecific antibody format, utilizing two identical tumor targeting domains and one CD3 targeting domain. The affinities for antigen binding are reduced, which allows for selective engagement and killing of high antigen-expressing tumor cells over low antigen-expressing normal cells. In preclinical models, XmAb 2+1 bispecific antibodies bound preferentially to tumor cells compared to normal cells and effectively recruited T cells to kill tumor cells selectively. We believe that these properties will be particularly important when developing bispecific antibodies against many solid tumor targets, which can have poor tolerability because such targets are often expressed on a range of normal tissues, including critical organs. Our initial candidate using the XmAb 2+1 format is XmAb819, an ENPP3 x CD3 bispecific antibody, and we expect to submit an Investigational New Drug (IND) application in 2021.
CD28 candidates: T cells in the tumor microenvironment require both T cell receptor (TCR) and co-stimulatory receptor engagement to achieve full activation. CD28 is a key immune co-stimulatory receptor on T cells; however, the ligands that activate T cells through CD28 are often not expressed on tumor cells. Targeted CD28 bispecific antibodies may provide conditional co-stimulation of T cells, for example, to T cells recognizing neoantigens or in concert with CD3 T-cell engaging bispecific antibodies. We have engineered XmAb bispecific antibodies to provide conditional CD28 co-stimulation of T cells, activating them when bound to tumor cells, and we are conducting preclinical studies of internal CD28 candidates. Under our collaboration with Janssen Biotech, Inc., we are applying our XmAb bispecific Fc technology to create and characterize CD28 bispecific antibody candidates through clinical development: XmAb14045, XmAb13676, and XmAb18087.against a prostate tumor target.
Tumor microenvironment (TME)TME activator candidates: we expanded the functionality of our bispecific Fc platform with a suite of tumor microenvironment (TME) activators that have been designed to promote tumor-selective T-cell activation by targeting multiple checkpoints or co-stimulating receptors. These candidates incorporate our Xtend technology for longer half-life. We are currently conducting Phase 1 studies for three TME activator candidatescandidates: XmAb717, XmAb841 and XmAb104.
Cytokine candidates: we have expanded the use of our bispecific Fc platform to engineer novel cytokine candidates, which are not antibodies but fusions of a heterodimeric Fc domain and immune signaling proteins. Our cytokine candidates are potency tuned to improve therapeutic index and incorporate our Xtend technology for longer half-life in their design. We are advancing three TME activator candidates through clinical development: XmAb20717, XmAb22841, and XmAb23104.
Cytokine candidates: the most recent expansion of our bispecific Fc platformhalf-life. XmAb306 (RO7310729), formerly XmAb24306, is our novel cytokine candidates. These cytokines are built on our bispecific Fc domain and have potency tuned to improve therapeutic index. These candidates also incorporate our Xtend technology for longer half-life. Our first cytokine candidate is XmAb24306, an IL-15/IL-15Ra cytokine complex built with our bispecific Fc domain. WeIL-15Ra-Fc fusion, which we believe that IL-15 cytokines, like XmAb24306, will beis a promising candidate for oncology combination therapies.therapies, and our partner Genentech is conducting a Phase 1 dose-escalation study. A second IL-15 cytokine candidate, which is engineered with a target-specific binding arm for immune cell targeting, is also being explored in preclinical studies.
XmAb564 is a wholly owned IL-2-Fc fusion that we intend to develop for the treatment of patients with autoimmune diseases. In January 2021, the IND application for XmAb564 was allowed by the FDA, and we plan to initiate a Phase 1 study in healthy volunteers for this candidate in early 2021.
6
We continue to invest in our bispecific Fcprotein engineering efforts to identify additional novel technologies and drug candidates.
Other XmAb Fc Technologies
Our business, research, and clinical efforts are in developing and advancing our bispecific Fc technology and pipeline of drug candidates in oncology. We have also designed additional XmAb Fc technologies and XmAb drug candidates that wecandidates. We have successfully partnered with other companies,our technologies and many drug candidates, and we will seek to continue to licenseseek additional partnering and partner to maximize their potential. Ourlicensing opportunities for these technologies and candidates. Additional XmAb Fc domains and technologies include:
1. | Immune Inhibitor Fc Domain – selective immune inhibition and rapid target clearance, targeting the receptor FcγRIIb; |
2. | Cytotoxic Fc Domain – increased cytotoxicity, targeting the receptors FcγRIIIa on natural killer (NK) cells and FcγRIIa on other immune system cells; and |
3. | Xtend™ Fc Domain – extended antibody half-life, targeting the receptor FcRn on endothelial cells. |
Drug Candidates in Clinical Development
Currently 20 drug candidates in clinical development have been engineered with one or more of our Fc technologies, and one incorporates our DN-TNF technology. Ten of the candidates that are being advanced by us and our partners have been engineered with our bispecific Fc domain for dual targeting and are bispecific antibody and cytokine candidates; one candidate in clinical development incorporates our immune inhibitor Fc domain, and seven candidates incorporate our cytotoxic or Xtend Fc domains.
| | | | |
| | | | |
Wholly Owned | | Co-developed with Partners | | Developed by Partners |
Plamotamab (XmAb13676) | | Vibecotamab (XmAb14045) | | Ultomiris* |
XmAb717 (XmAb20717) | | XmAb306/RG6323 (XmAb24306) | | Monjuvi* |
Tidutamab (XmAb18087) | | | | VIR-7831 |
XmAb841 (XmAb22841) | | | | XPro1595/INB03/Quellor™ |
XmAb104 (XmAb23104) | | | | AIMab7195 |
XmAb564 (XmAb27564) | | | | Elipovimab (GS-9722) |
XmAb698 (AMG 424) | | | | VIR-3434 |
| | | | Novartis bispecific antibody |
| | | | AMG 509 |
| | | | VIR-2482 |
| | | | GS-9723 |
5
*Alexion and MorphoSys are conducting additional Phase 3 studies in new indications with these candidates.
XmAb Bispecific Fc Drug Candidates
There are currently seven bispecificCurrently 10 drug candidates that have been engineered with our bispecific Fc domain throughare in clinical or late preclinical development: fourdevelopment. Six candidates are wholly owned and are being evaluated by us in Phase 1 studies,studies. We are co-developing two candidates have Investigational Newwith partners. In addition, partners are advancing two bispecific antibody candidates through clinical development. Additional candidates are advancing through the preclinical stages of development. Drug applications (INDs) that have been allowed by the FDAcandidates with our bispecific Fc domain, both bispecific antibodies and for which we plan to initiatecytokines, in clinical trials in 2019, and one candidate for which we expect to submit an IND application to the FDA in 2019.development include:
| 1. | Plamotamab is a bispecific antibody that targets CD20, an antigen on B-cell tumors, and CD3, an activating receptor on T cells. In February 2017, we dosed the first patient in an open-label, Phase 1, multiple-dose, dose escalation study to assess the safety, tolerability, and preliminary anti-tumor activity of plamotamab in patients with B-cell malignancies. At the ASH Annual Meeting in December 2019, we presented preliminary safety and anti-tumor activity of plamotamab, including from patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL). We are enrolling patients in the ongoing dose-escalation study, and we are planning to initiate additional studies for plamotamab in 2021 including a Phase 1/2 study evaluating the combination of |
7
| plamotamab, tafasitamab (Monjuvi) and lenalidomide in patients with relapsed or refractory DLBCL, an aggressive type of NHL. |
| XmAb717 is a bispecific antibody that targets PD-1 and CTLA-4, two immune checkpoint receptors, to selectively activate the tumor microenvironment, and it is being developed in multiple types of solid tumors, including for patients with castration-resistant prostate cancer. In July 2018, we dosed the first patient in an open-label Phase 1 dose-escalation and expansion study to assess the safety, tolerability, and preliminary anti-tumor activity of XmAb717 in patients with selected solid tumors. We presented updated data from the study at the Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in November 2020. In the study's escalation phase, a dose of 10 mg/kg was identified as the recommended dose for the multi-cohort, parallel-group expansion phase, based on an observation of consistent proliferation of both CD8+ and CD4+ T cells, indicative of dual checkpoint blockade, and a complete response (CR) in one patient with melanoma. At the data cut off on September 30, 2020, 89 patients had been treated at the recommended dose in five dose expansion cohorts that enrolled patients with melanoma (n=20), renal cell carcinoma (RCC, n=11), non-small cell lung cancer (NSCLC, n=20), castration-resistant prostate cancer (CRPC, n=18) and other cancers without approved checkpoint therapies (n=20). XmAb717 was generally well-tolerated, and the most common treatment-related adverse events were immune-related adverse events (irAEs); however, rates of irAEs, including colitis, were lower than typically observed with CTLA-4 blockade. With exceptions for rash and increases in transaminases, other Grade 3 or higher irAEs were reported for no more than three patients each. The efficacy analysis included 42 evaluable patients at the recommended dose level. A complete response was observed in a patient with melanoma (1/10), and partial responses were observed in multiple tumor types, including melanoma (2/10), RCC (1/4), NSCLC (2/14), CRPC (1/4), and ovarian cancer (1/5). The objective response rate across cohorts was 19.0% (8/42). Across the expansion cohorts, approximately half of evaluable patients had at least 10% tumor shrinkage from baseline assessments, and nearly all these reductions occurred in patients with prior checkpoint inhibitor treatment. The median duration of response was 119 days at the time of the data cut off, and 24 patients remained on treatment. Of nine patients with prostate cancer who had baseline and follow-up prostate-specific antigen (PSA) assessments, one achieved a PSA reduction of greater than 50 percent. Two additional patients achieved reductions of greater than 30 percent, one of whom had an unconfirmed partial response by RECIST. Six of these nine patients remained on therapy as of the cut-off date. In the first half of 2021, we plan to initiate a Phase 1b study of XmAb717 for patients with certain molecular subtypes of CRPC, as a monotherapy or in combination depending on the subtype, as these patients represent a high unmet medical need. |
| 3. | Vibecotamab is a bispecific antibody that targets CD123, an antigen on acute myeloid leukemia (AML) cells and leukemic stem cells, and CD3, We presented updated data from the study at the American Society of Hematology (ASH) Annual Meeting in December 2020. At data cut off on October 28, 2020, 112 heavily pretreated patients with relapsed or refractory AML had received vibecotamab. Cytokine release syndrome (CRS) was the most common toxicity occurring in 61% of patients (n=68), and 9% of patients (n=10) experienced CRS at Grade 3 or higher. The majority of CRS was observed in the first dose and was generally manageable with premedication. Additional mitigation measures included selecting a lower priming dose, avoiding weekly dose step-up, and more frequent dosing in the first week to allow a higher cumulative exposure and to avoid the potential CD123 antigen sink. There was no evidence of drug related myelosuppression. Neurological events were infrequent and primarily Grade 1 and Grade 2 headaches. The efficacy analysis included 54 evaluable patients who received a dose of at least 0.75 mcg/kg, completed at least the first cycle of treatment and had at least one post-treatment disease assessment. |
We presented initial data from the study in December 2018 at the American Society8
In February 2019, we received notice from the FDA placing the XmAb14045 study on partial clinical hold due to safety issues of cytokine release syndrome and pulmonary toxicities. Under the partial hold, existing subjects on the trial may continue to receive dosing; however, no new subjects may be enrolled pending FDA review of a clinical hold response.
The partial hold was initiated following recent safety reports Xencor submitted to the FDA on two patient deaths that were considered at least possibly related to XmAb14045. One patient experienced cytokine release syndrome (CRS) after their first dose, the treatment of which was complicated by the patient’s decision to withdraw care. One subject developed acute pulmonary edema following several doses of XmAb14045. Items to be addressed in the response include analysis of CRS cases per dosing level, efficacy information, and strategies to mitigate the observed toxicities.
We are coordinating a response to the partial hold by the FDA with our partner, Novartis, and plan to continue development of XmAb14045 pending resolution of the partial hold.
| Two patients achieved complete remission (CR), and three patients achieved a CR with incomplete hematologic recovery. Additionally, two patients reached a morphologic leukemia-free state, and one patient experienced partial remission, as assessed by the investigator. The overall response rate (ORR) was 15% (n=8/54). Biomarker analyses suggest that low baseline leukemic burden and low PD-1 expression on CD4+ and CD8+ T cells are independent predictors of response. Seven responders had a baseline blast count less than or equal to 25% blasts in bone marrow. The ORR increased to 26% (n=7/27) when using this threshold to define the population with low disease burden for the analyses. In 2021, pending final dose escalation data and agreement with our partner, Novartis, we plan to initiate additional clinical studies evaluating vibecotamab. |
| Tidutamab is a bispecific antibody |
6
|
|
In October 2020, we presented initial dose-escalation data in patients with NETs at the North American Neuroendocrine Tumor Society’s 2020 Multidisciplinary NET Medical Virtual Symposium (NANETS). Tidutamab was generally well tolerated at the recommended dose identified for the expansion portion of the study, a 0.3 mcg/kg priming dose and subsequent 1.0 mcg/kg repeated doses. Analysis of peripheral blood biomarkers indicated that tidutamab induced acute and sustained T-cell activation at the recommended dose for expansion. The analysis also indicated a dose-dependent increase in proliferation and activation markers on CD8-positive effector T cells, which is consistent with tidutamab's mechanism of action. Fourteen patients, including 12 across the first three dose-escalation cohorts and two in the expansion cohort, were included in the analysis to describe clinical activity. The best overall response was stable disease, with a disease control rate of 43% and a median duration of treatment of approximately seven months. Completion of enrollment in the expansion cohort and longer follow-up are required to evaluate progression-free survival and the clinical utility of tidutamab in this NET patient population.
Because tidutamab induced sustained activation of cytotoxic T cells and engagement of the SSTR2 target, as designed, and has an encouraging safety profile, we plan to initiate a clinical study for tidutamab in patients with Merkel cell carcinoma and small cell lung cancer, SSTR2-expressing tumor types known to be responsive to immunotherapy, in early 2021.
|
|
|
|
|
|
7. |
|
9
| with atezolizumab. |
| 8. | AMG 509 is a STEAP1 x CD3 bispecific antibody candidate for the treatment of patients with prostate cancer.In December 2019, Amgen Inc. initiated a Phase 1 clinical study with AMG 509, a 2+1 bispecific antibody candidate that was developed with our bispecific Fc technology under our collaboration with them. Amgen is currently enrolling patients in a Phase 1 study of AMG 509 in patients with metastatic castration-resistant prostate cancer (mCRPC). |
| 9. | XmAb698 (AMG 424), a CD38 x CD3 bispecific antibody candidate, was developed in the Amgen collaboration and was being advanced by Amgen in a Phase 1 study. In 2020, Amgen notified us that they were terminating the study, and the rights to |
| 10. | NovartisXmAb undisclosed bispecific antibody candidate: in December 2019, Novartis initiated a Phase 1 clinical study with an undisclosed bispecific antibody candidate that was developed with our bispecific Fc technology under our collaboration with them. |
XmAb Immune Inhibitor Fc Candidates
We have developed two clinical candidates using our Immune Inhibitor Fc Domain:
XmAb5871AIMab7195 (XmAb7195) uses our XmAb Immune Inhibitor Fc Domain and is designed to reduce blood serum levels of IgE, which mediates allergic responses and allergic disease. In February 2020, we licensed this drug candidate to Aimmune Therapeutics, Inc., now a wholly owned subsidiary of Nestlé S.A., which is advancing the candidate in clinical studies for allergic indications.
Obexelimabtargets CD19 with its variable domain and uses our XmAb Immune Inhibitor Fc Domain, which is designed to inhibit the function of B cells, an important component of the immune system. We believe that XmAb5871obexelimab has the potential to address a key unmet need in autoimmune diseases due to its combination of potent reversible B-cell inhibition without B-cell depletion, enabling the immune system to resume natural function once treatment is no longer needed. We have completedare exploring opportunities to continue development of obexelimab with partners.
XmAb Cytotoxic Fc and Xtend Candidates
Currently, one drug engineered with our Xtend Fc Domain and one drug we engineered with our XmAb Cytotoxic Fc Domain are marketed commercially by partners. In addition, our partners are advancing eight clinical programs with antibodies engineered with XmAb technologies through clinical development: three programs are in Phase 3, one program is in Phase 2, clinical trials for XmAb5871and four programs are in three autoimmune disease areas: Systemic Lupus Erythematosus (SLE), IgG4-Related Disease (IgG4-RD), and Rheumatoid Arthritis (RA).Phase 1. Other partners are conducting preclinical studies of drug candidates engineered with these XmAb technologies.
| ● | MorphoSys AG: In 2020, Monjuvi was approved for marketing by the U.S. FDA for the treatment of certain adult patients with DLBCL. Tafasitamab’s marketing authorization application is under review by European regulators, and MorphoSys is also conducting studies of tafasitamab in additional B-cell indications. |
| ● | Alexion Pharmaceuticals, Inc.: Ultomiris was approved for marketing by the U.S. FDA in 2018, and Alexion is conducting Phase 3 studies of Ultomiris in additional neurology and nephrology indications. |
| ● | Gilead Sciences, Inc.: Gilead is advancing HIV candidates in clinical development that are broadly neutralizing antibodies that incorporate our Fc technologies. Gilead is conducting Phase 1 clinical studies of elipovimab (GS-9722) and GS-9723. |
| ● | Vir Biotechnology, Inc.: Vir is advancing three candidates in clinical development. VIR-7831 is an antibody that is being investigated in a Phase 3 study as a potential treatment for the treatment of patients with COVID-19. VIR-2482 is being evaluated in a Phase 1/2 study as a universal prophylactic for influenza A. VIR-3434 is being evaluated in a Phase 1 study as a potential treatment for patients with hepatitis B virus infection. |
10
| ● | Omeros Corporation, Viridian Therapeutics, Inc. and Catabasis Pharmaceuticals, Inc. each are conducting preclinical studies with candidates that incorporate our XmAb technologies. |
XPro1595
SLE: in orderIn October 2017, we licensed the rights to assess the effect of XmAb5871 on SLE disease activity inXPro1595, a shorter timeframe and enrolling fewer patients than standard SLE trials, we completedproprietary TNF inhibitor candidate to INmune Bio, Inc. INmune is currently conducting a Phase 2 study with a novel design that sought to reduce the confounding effects of background immunosuppressive medication.
7
The randomized, double-blind, placebo-controlled, Phase 2 study enrolled 104in hospitalized patients with moderate to severe, non-organ threatening SLE across 20 sitesrespiratory symptoms from COVID-19 infection, as Quellor™; a Phase 1 study in the United States. Patients discontinued background immunosuppressive medication and received a short course of intramuscular steroids to quiet SLEpatients Alzheimer’s disease, activity. Patient lupus activity was evaluated using the SLE Disease Activity Index (SLEDAI) and the British Isles Lupus Activity Group (BILAG) scoring. Patients achieving the required disease activity improvement (SLEDAI decrease ≥4 points, or ≥1 grade decrease in ≥1 BILAG A or B score) were randomized 1:1 to receive XmAb5871 (n = 52) or placebo (n = 52) every 14 days for up to 16 doses.
In October 2018, we presented topline data from the study at the American College of Rheumatology (ACR) annual meeting. The primary endpoint of the study was the proportion of patients with no loss of improvement (LOI) (i.e., maintenance of improvement) in the efficacy-evaluable population, defined as those who completed Day 225, had LOI, or discontinued due to a drug-related adverse event. LOI was defined as a SLEDAI increase ≥4 points or a new BILAG A or B score and physician intent to treat with rescue medication. Improvement was maintained at Day 225 by 42% of patients (21/50) in the XmAb5871-treated arm, compared to 28.6% of patients (12/42) in the placebo-treated arm, which did not meet the primary endpoint for statistical significance (p = 0.18). The efficacy-evaluable population excludes 10/52 (19%) placebo patients and 2/52 (4%) XmAb5871-treated patients who withdrew from the study for reasons other than LOI or adverse event. These exclusions resulted in higher placebo response rates compared to the intent-to-treat (ITT) population. In the ITT population, improvement was maintained by 40.4% of patients (21/52) in the XmAb5871-treated arm, compared to 23.1% of patients (12/52) in the placebo-treated arm which results in an improved statistical significance (p = 0.06).
Secondary endpoints included evaluations of time to LOI and safety and tolerability of XmAb5871. Patients in the efficacy-evaluable population treated with XmAb5871 experienced a statistically significant longer time to LOI (median = 230 days, hazard ratio = 0.53, p = 0.025), compared to placebo-treated patients (median = 131 days), a 76% improvement in median time to LOIXPro1595; and a 47% reduction in risk of LOI. XmAb5871 was well tolerated, and its safety profile was consistent with previous trials.
IgG4-RD: In November 2017, we presented final data from a Phase 21 study of XmAb5871 in patients with IgG4-RD at the ACR annual meeting for the 15 patients that had been enrolledadvanced cancers, as INB03.
Collaborations, Partnerships and received one or more doses of 5 mg/kg of XmAb5871. The data indicated that XmAb5871 was well tolerated by patients receiving drug in the study. Three patients had minor, transient gastrointestinal side-effects during the first infusion; all completed the study. Two serious adverse events (SAEs) unrelated to XmAb5871 were observed in one patient, pneumonia and recurrence of pneumonia due to non-compliance with antibiotic therapy (patient completed study). All other XmAb5871-related adverse events (AEs) were graded as mild or moderate, and no treatment related AE was reported in more than two patients. Three patients discontinued the study early.Licensing Arrangements
12 of the 15 patients (80%) completed the trial and all 12 achieved the primary endpoint of at least a 2-point reduction in IgG4-RD Responder Index (RI) on day 169. None of the 12 required corticosteroids (CS) after month two. Eight patients achieved remission (IgG4-RD RI of zero and no CS after two months) and the other four patients achieved an IgG4-RD Responder Index score of <=4 at Day 169. 14 of 15 patients (93%) achieved a decrease of ≥ 5 in the IgG4-RD RI.
In May 2017, we received Orphan Drug designation from the FDA for XmAb5871 for the treatment of IgG4-RD. In January 2018, we received Orphan Medicinal Product designation from the European Commission.
RA: In June 2015, we announced results from a Phase 1b/2a placebo-controlled trial of XmAb5871 in patients with rheumatoid arthritis (RA). The results indicated that XmAb5871 was generally well tolerated. Although the trial was not designed to observe a statistically significant difference in efficacy results between XmAb5871 and placebo treated patients, sufficient efficacy trends were seen to warrant continued clinical development of XmAb5871 in autoimmune indications. A numerically increased proportion of patients with improvements across several measurements of disease activity were observed in the XmAb5871 treated groups compared to placebo.
8
Subcutaneous bioequivalence: In October 2016, we completed a Phase 1 bioequivalence trial for XmAb5871 using a subcutaneous (SC) formulation. XmAb5871 had a favorable safety profile and was well-tolerated. Pharmacokinetics and bioavailability data from the trial support an every-other-week dosing schedule, and we expect that further clinical studies will be conducted with XmAb5871 in a SC formulation.
We believe that the clinical trials that we have conducted with XmAb5871 show the potential of this molecule in treating B-cell mediated autoimmune indications. We are looking to continue developing XmAb5871 in additional late-stage clinical trials with a partner that has the resources and infrastructure to maximize the potential of this compound.
XmAb7195 uses our Immune Inhibitor Fc Domain and targets IgE with its variable domain, and this drug candidate is being developed for the treatment of severe asthma and allergic diseases. XmAb7195 uses three distinct mechanisms of action to reduce blood serum levels of IgE, which mediates allergic responses and allergic disease.
In January 2015, we reported top-line interim data from Part 1 of the Phase 1a trial of XmAb7195, in which healthy volunteers received a single intravenous (IV) dose. In 2015, we continued the Phase 1a trial of XmAb7195, treating subjects with high baseline IgE levels, and in June 2015, we announced an expansion of the trial, adding cohorts of subjects that receive two IV doses of XmAb7195. We announced complete data from these studies in May 2016.
In September 2016, we initiated a multi-dose Phase 1b trial for XmAb7195 with a SC formulation. The first part of this study was an open-label bioequivalence trial evaluating four once-weekly doses of SC XmAb7195 ranging from 0.1 to 1.0 mg/kg in cohorts of six healthy volunteers. The second part of the trial, which we began in October 2016, was a randomized, double-blinded, placebo-controlled multiple-ascending dose study in atopic patients of SC XmAb7195 at doses of 1.5 and 2.0 mg/kg. Half-life of SC XmAb7195 ranged from 3.6 - 4.9 days, comparable to the previously reported half-life of 3.9 days of intravenously administered XmAb7195. Bioavailability after the fourth dose exceeded 50%, which is typical for monoclonal antibodies, and drug concentration levels increased with successive doses.
SC administration of XmAb7195 was well tolerated. No severe AEs or serious treatment-emergent AEs occurred during the study. The most frequently occurring treatment-emergent AEs were injection-site related, including erythema, pruritus and/or urticaria, and most were mild. No diffuse urticaria or other systemic hypersensitivity reactions were reported. No apparent consistent effect of SC XmAb7195 on platelet count was seen when dosed at 0.1 - 1.0 mg/kg weekly for four weeks. At 1.5 - 2.0 mg/kg weekly for four weeks mild platelet count reductions were observed. Four of 15 patients in the 2.0 mg/kg group had at least one platelet count of less than 150 x 103/L at some time point. The lowest count observed was 126 x 103/L, and a recovery to within normal range occurred within a few days of the doses.
In 23 of 27 (85%) subjects with detectable baseline free IgE (≥ 9.59 ng/mL) (median 76.2 ng/mL, range: 17.4-846 ng/mL), treated with four weekly SC XmAb7195 doses of 0.3 to 2.0 mg/kg, free IgE was suppressed to below the level of quantification (BLQ) at some time point during the treatment period. In 20 of the 27 (74%) subjects, once suppression of free IgE to BLQ was observed, BLQ values were maintained for the remainder of the treatment period and for at least seven days following the last dose. Similarly, in the subgroup of atopic subjects, 14 of 14 (100%) subjects with detectable baseline free IgE (median 150.0 ng/mL, range: 46.4-846 ng/mL) treated with four weekly SC XmAb7195 doses of 1.5 to 2.0 mg/kg, free IgE was suppressed to BLQ at some time point during the treatment period. In 12 (86%) atopic subjects, once suppression of free IgE to BLQ was observed, BLQ values were maintained for the remainder of the treatment period and for at least seven days following the last dose.
9
In 28 of 31 (90%) subjects with detectable baseline total IgE (≥ 2.0 IU/mL) (median 68.1 IU/mL, range: 7.13-736 IU/mL) treated with four weekly SC XmAb7195 doses of 0.3 to 2.0 mg/kg, total IgE was suppressed to BLQ at some time point during the treatment period. In the other three subjects, total IgE levels were reduced to < 1% of baseline values. In 23 of 28 (82%) subjects, once suppression of total IgE to BLQ was observed, BLQ values were maintained for the remainder of the treatment period and for at least seven days following the last dose. Similarly, in the subgroup of atopic subjects, 12 of 14 (86%) subjects with detectable baseline total IgE (median 153.5 IU/mL, range: 38.9-736.0 IU/mL) treated with four weekly SC XmAb7195 doses of 1.5 to 2.0 mg/kg, total IgE was suppressed to BLQ at some time point during the treatment period. In the other two atopic subjects, total IgE levels were reduced to < 1% of baseline values. In eight of 12 (67%) subjects once suppression of free IgE to BLQ was observed, BLQ values were maintained for the remainder of the treatment period and for at least seven days following the last dose. In three of the other four atopic subjects that had suppression of total IgE level to BLQ, subsequent total IgE levels through seven days after the fourth dose were < 2% of baseline values.
These results support SC delivery for future development, and pharmacokinetic/pharmacodynamic modeling is proceeding to determine the optimal dosing schedule. Xencor is seeking a partner for continued development of XmAb7195.
Collaborations
An importantkey part of our business strategy is to leverage the value of our bispecific Fcprotein engineering capabilities, XmAb technologies, and drug candidates with partnerships, collaborations and collaborations. Our goallicenses. Through these arrangements we generate revenues in suchthe form of upfront payments, milestone payments and royalties. For partnerships isfor our drug candidates, we aim to a retain a major economic interest in these candidates through transactions that allow us to retain major geographic commercial rights, provide for profit-sharing on future sales of approved products, include co-development options, and also the right to conduct independent clinical studies with drug candidates thatdeveloped in the collaboration.
Examples of arrangements we develop or, are developedhave entered with our bispecific technologies,partners include:
| ● | Product Licenses: Genentech, MorphoSys AG, Nestlé S.A., Novartis AG, INmune Bio, Inc. |
| ● | Novel Bispecific Antibody Collaborations: Janssen Biotech, Inc., Astellas Pharma, Inc., Amgen Inc., Novartis AG |
| ● | Technology Licensing Agreements: Alexion Pharmaceuticals, Inc., Vir Biotechnology, Inc., Gilead Sciences, Inc., Omeros Corporation, Viridian Therapeutics, Inc., Catabasis Pharmaceuticals, Inc. |
| ● | Strategic Collaborations: MorphoSys AG, Atreca, Inc., The University of Texas MD Anderson Cancer Center |
Product Licenses
Product licenses are arrangements in the form of retention of U.S. commercialwhich we have internally developed drug candidates, and based on a strategic review we licensed partial or full rights profit-sharing interest, co-development opportunities, upfront payments, milestones,to third parties to continue development and potential royalties on approved drug candidates.commercialization. We seek to partner with companiespartners that can provide infrastructure for late stage development,and resources to successfully develop our drug candidates, have a track record of successfully developing and commercializing oncology drug candidates,medicines, or have a pipelineportfolio of developmentdevelopment-stage candidates and commercial compounds for potential combinationcommercialized medicines which could potentially be developed in rational combinations with our bispecific compounds. The plug-and-play nature of our technologies allows us to license access to our bispecific Fc platform to partners with limited effort or resources on our part. We are co-developing two of our current drug candidates with partners, another partner has advanced into development two candidates that have been designed using our bispecific Fc technology, and there are others in preclinical development.candidates.
Our bispecific collaborations include:Genentech
Genentech
In February 2019, we entered into We received an upfront payment of $120.0 million. We are eligible to receive up to $160.0 million in clinical milestone payments for XmAb306, up to $180.0 million in clinical milestone payments for each new Collaboration Product, and a research and licensean agreement with Genentech (the Genentech Agreement) to develop and commercialize novel IL-15 cytokine therapeutics that use our bispecific Fc technology, including XmAb24306, and otherXmAb306, declared as a Collaboration Products, inProduct under the areas of cancer immunotherapy.agreement. We willare jointly collaboratecollaborating on the worldwide development of XmAb24306 and other IL-15 cytokine therapeutics, each a Collaboration Product,XmAb306 with Genentech maintaining worldwide commercialization rights, subject to us having a co-promotion option in the U.S. We retainedretain the right to perform clinical studies of Collaboration Productswith XmAb306 at our sole expense in combination with other therapeutic agents, subject to certain requirements.restrictions. Genentech received a worldwide exclusive license to XmAb24306XmAb306.other Collaboration Products. The key aspectsa 45% share of the agreement include:
|
|
|
|
|
|
1011
|
|
Thethe same percentage rate. We are sharing in 45% of development and commercialization costs of Collaboration Products, while Genentech Agreementwill pay for commercial launch costs. We are conducting a two-year joint research program with Genentech to discover additional IL-15 programs.
MorphoSys AG
In July 2020, the FDA approved Monjuvi® (tafasitamab-cxix) in combination with lenalidomide for treating certain patients with DLBCL. Tafasitamab, which we engineered with an XmAb Cytotoxic Fc Domain, is subjectthe second product with XmAb technology to customary closing conditions, including clearance underbe approved by the Hart-Scott-Rodino Antitrust Improvements Act,FDA.
In 2010, we licensed exclusive worldwide rights to develop and closing is expectedcommercialize tafasitamab (formerly MOR208 and XmAb5574) to occurMorphoSys. In 2020, we earned a total of $37.5 million in regulatory milestones and royalties of $1.5 million on net sales. We are also eligible to receive up to $98.0 million in additional milestones for development of tafasitamab in additional oncology indications and $50.0 million in sales milestones across all indications. We are entitled to receive tiered royalties in the first quarter of 2019.high-single digit to low-double digit percent range on net sales. Monjuvi is co-commercialized in the U.S. by MorphoSys and Incyte Corporation. The European Marketing Authorization Application for tafasitamab is currently under review by the European Medicines Agency.
We believe that the Genentech collaboration maximizes the potential value of our XmAb24306 candidate and other potential Collaboration Products.
NovartisNestlé S.A./Aimmune Therapeutics, Inc.
In February 2020, we granted Aimmune Therapeutics, Inc., an exclusive worldwide license to develop and commercialize XmAb7195, which was renamed AIMab7195. We received an upfront payment of $9.6 million in cash and shares of Aimmune common stock. Aimmune was subsequently acquired by Nestlé S.A. Nestlé is responsible for all further development and commercialization activities for AIMAb7195. We are eligible to receive up to $385.0 million in milestones, which includes $22.0 million in development milestones, $53.0 million in regulatory milestones and $310.0 million in sales milestones, and tiered royalties in the high-single to mid-teen percent range on net sales of approved products. Nestlé is planning additional studies of AIMab7195.
Novartis AG
In connection with our June 2016 we entered into a Collaboration and License Agreement with Novartis (the Novartis Agreement), we granted Novartis certain exclusive rights to research, develop, and commercialize vibecotamab. We are eligible to receive up to $325.0 million in milestone payments in connection with the development of vibecotamab, including $90.0 million in development milestones, $110.0 million in regulatory milestones, and $125.0 million in sales milestones, and low-double digit royalties on sales of approved products in all territories outside the United States. We retained the commercialization rights to vibecotamab in the U.S. We and Novartis are co-developing vibecotamab worldwide and are sharing development costs equally.
INmune Bio, Inc.
In October 2017, we entered into an agreement with INmune Bio, Inc., in which we provided INmune with an exclusive license to our XPro1595 drug candidate. In connection with the license, we received 1,585,000 shares of INmune common stock and an option to acquire up to 10% of the outstanding shares of INmune for $10.0 million. We are also eligible to receive a percentage of sublicensing revenue received for XPro1595 and royalties in the mid-single digit percentage range on the sale of approved products. INmune is currently conducting a Phase 2 study in hospitalized patients with respiratory symptoms from COVID-19 infection, as Quellor™; a Phase 1 study in patients Alzheimer’s disease, as XPro1595; and a Phase 1 study in patients with advanced cancers, as INB03.
Private Company
In November 2020, we entered into an agreement with a newly formed, privately held biotechnology company to which we licensed the exclusive worldwide rights to develop and commercialize three preclinical-stage Fc-engineered drug candidates for autoimmune disease: XmAb6755, XPro9523 and XmAb10717. These programs incorporate an Xtend Fc Domain, a Cytotoxic Fc Domain, or both. We received a 15% equity interest in the company, and we will also
12
receive royalties on net sales of approved products in the mid-single digit to mid-teen percentage range.
Novel Bispecific Antibody Collaborations
Novel bispecific antibody collaborations are arrangements in which our partner seeks to create a bispecific antibody using one or more of our XmAb bispecific technologies. Our partners provide an antibody or an antigen against tumors, and other Fc engineeredwe conduct limited research and development activities to create potential bispecific antibody drug candidates. Key aspectscandidates for further development and commercialization by our partners.
Janssen Biotech, Inc.
In November 2020, we entered into an agreement, which became effective in December 2020, with Janssen Biotech, Inc., to develop XmAb bispecific antibodies against CD28 and an undisclosed prostate tumor target, for the potential treatment of patients with prostate cancer. Under the agreement, include:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
11
Tablewe will conduct research activities to develop CD28 bispecific drug candidates for further development by Janssen. Preclinical activities and all clinical development, regulatory and commercial activities will be conducted by Janssen, which has exclusive worldwide rights to develop and commercialize the novel drug candidates developed in the collaboration. We received a $50.0 million upfront payment and are eligible to receive a total of Contents$662.5 million in milestone payments which include $161.9 million in development milestones, $240.6 million in regulatory milestones, and $260.0 million in sales milestones. We are also eligible to receive tiered royalties in the high-single to low-double digit percentage range on net sales.
Upon development of a bispecific candidate by Janssen through proof of concept, the agreement provides us the right to opt-in to fund 20% of development costs and to perform up to 30% of detailing efforts in the U.S. If we exercise this right, we will be eligible to receive tiered royalties in the low-double digit to mid-teen digit percentage range.
|
|
Both we and Janssen also have the right to access predefined agents from each other's portfolios to evaluate potential combination therapies in prostate cancer, subject to certain limitations.
Astellas Pharma, Inc.
In March 2019, we entered into an agreement with Astellas Pharma, Inc., under which we applied our XmAb bispecific Fc technology to an antigen pair provided by Astellas and generated bispecific antibody candidates for further certain characterization and testing, and in 2019, we completed delivery of the candidates to Astellas for development and potential commercialization. Astellas was granted a worldwide exclusive license, with the right to sublicense products in the field created by the research activities. We received an upfront payment of $15.0 million, and we are eligible to receive up to $240.0 million in milestones which include $32.5 million in development milestones, $57.5 million in regulatory milestones and $150.0 million in sales milestones and royalties on net sales in the high-single to low-double digit percentage range. In 2020, we received a $2.5 million milestone payment related to Astellas advancing a bispecific candidate into IND enabling studies, and we are eligible to receive an additional $30.0 million in development milestones as the program advances.
Amgen Inc.
In September 2015, we entered into a research and licensean agreement with Amgen Inc. (Amgen) (the Amgen Agreement) to develop and commercialize productsbispecific antibody product candidates using our proprietary XmAb bispecific Fc technology. Under the
We granted Amgen Agreement, we licensedan exclusive license to the rights to our internally developed, preclinical CD38 x CD3 preclinical program, and they developed AMG 424. In May 2020, Amgen notified us it was terminating its rights with respect to the CD38 x CD3 program, including AMG 424. Under the terms of the agreement, the rights to the AMG 424 program reverted to us. We renamed the program XmAb698 and plan to initiate a new study for it in 2021.
Amgen also applied our XmAb bispecific antibody candidate to Amgen and also agreed to apply our bispecificFc technology to five previously identified Amgen antibodies.create AMG 509, a STEAP1 x CD3 XmAb 2+1 bispecific antibody. We have received $55.5a total of $60.5 million in upfront payments and milestone payments and are eligible to receive up to an additional $600$255.0 million in future development, regulatory and sales milestone payments in total for the STEAP1 x
13
CD3 program and royalties on net sales.
Novartis AG
In connection with our June 2016 agreement with Novartis, we also applied our XmAb bispecific Fc technology to two target pair antibodies selected by Novartis. Novartis is responsible for development and commercialization of these programs. We are eligible to receive up to $250.0 million in milestone payments for each program which includes $50.0 million in development milestones, $100.0 million in regulatory milestones, and $100.0 million in sales milestones and royalties in the mid-single digit percent range on net sales of approved products. Amgen isWe completed delivery of one bispecific antibody candidate in 2017 and a second bispecific antibody candidate in 2018. In December 2019, Novartis dosed the first patient in a Phase 1 study of an undisclosed bispecific antibody candidate, and we received a $10.0 million milestone payment.
We have the right to participate in the development and commercialization of one of these programs prior to submission of an IND for such program. If we elect to participate in development, we will assume 25% of the worldwide development costs for the program and 50% of commercialization costs and will receive 50% of the U.S. profits on net sales of the product.
Technology Licensing Agreements
We enter into technology licensing agreements in which we license access to one or more of our XmAb Fc technologies on a restricted basis, typically to our XmAb Cytotoxic Fc Domain and/or our Xtend Fc Domain. Our partners are responsible for all research, development and commercialization activities of the bispecific candidates underdrug candidates. The plug-and-play nature of XmAb technologies allows us to license access to our platforms with no internal research and development activities required of us.
Alexion Pharmaceuticals, Inc.
Ultomiris® (ravulizumab-cwvz) was the Amgen Agreement. Current programsfirst antibody incorporating XmAb Fc technology to be approved by the U.S. FDA for commercial marketing. It is approved in development from the Amgen collaboration include:
|
|
|
|
XmAb LicensingU.S., Europe and Technology Partnerships
There are currently four partnershipsJapan for the treatment of adult patients with XmAb candidates in development.
paroxysmal nocturnal hemoglobinuria (PNH) and for the treatment of patients with atypical hemolytic uremic syndrome (aHUS). Ultomiris is commercialized by Alexion Pharmaceuticals, Inc.
In 2013, we licensed Alexion Pharmaceuticals, Inc. (Alexion) the right to access our Xtend Fc domain, andwhich Alexion incorporated it in developing Ultomiris,used to develop an improved version of Alexion’s commercialized Soliris product. The Xtend technology has increased the circulating half-life of Ultomiris by over three foldthree-fold compared to Soliris and extended the dosing schedule to bimonthly for Ultomiris compared to biweekly for Soliris. During 2020, we received a $10.0 million sales milestone payment and recorded royalty revenue of $16.2 million. We are eligible to receive an additional $20.0 million in sales milestones and a low-single digit percent royalty on the sale of approved products.
Vir Biotechnology, Inc.
In 2018, Alexion submitted marketing authorization applicationsAugust 2019, we entered into an agreement with Vir Biotechnology, Inc., in which we provided Vir a non-exclusive license to our Xtend technology for Ultomiristwo targets in infectious disease. We received an upfront payment, and we are eligible to receive total milestones of $155.0 million, including $5.0 million of development milestones, $30.0 million of regulatory milestones and $120.0 million of sales milestones. We are also eligible to receive royalties on the regulatory authoritiesnet sales in the U.S., Europelow single digit percentage range. Vir has advanced two programs under this agreement. VIR-2482 is being evaluated in a Phase 1/2 study as a universal prophylactic for influenza A, and Japan;VIR-3434 is being evaluated in a Phase 1 study as a potential treatment for patients with hepatitis B virus infection.
In March 2020, we entered into a second agreement in which we provided Vir a non-exclusive license to our Xtend technology to extend the half-life of novel antibodies Vir is investigating as potential treatments or for patients with COVID-19. Vir is responsible for all research, development, regulatory and commercial activities for COVID-19 antibodies, and we are eligible to receive royalties on the net sales of approved products in the mid-single digit
14
percentage range. Vir is currently conducting Phase 3 studies of VIR-7831 as a potential treatment for the treatment of adult patientsCOVID-19.
Gilead Sciences, Inc.
In January 2020, we entered into an agreement with paroxysmal nocturnal hemoglobinuria (PNH)Gilead Sciences, Inc., in which we provided Gilead an exclusive license to our Cytotoxic Fc and in December 2018, Alexion received FDA approval.Xtend Fc technologies for an initial identified antibody and options for up to three additional antibodies, all broadly neutralizing anti-HIV antibodies. Gilead has exercised its options for all three additional antibodies. Gilead is responsible for all development and commercialization activities. During 2018,2020, we received upfront and option payments of $13.5 million, and for each of four antibodies, we are eligible to receive up to $67.0 million in milestones, which includes $10.0 million in development milestones, $27.0 million in regulatory milestones and $30.0 million in sales milestones. We are also eligible to receive royalties in the low-single digit percentage range on net sales of approved products. Gilead has advanced antibodies, including elipovimab (GS-9722) and GS-9723, into clinical studies.
Omeros Corporation
In August 2020, we entered into an agreement with Omeros Corporation, in which we provided Omeros a non-exclusive license to our Xtend Fc technology, an exclusive license to apply our Xtend Fc technology to an initial identified antibody and options to apply our Xtend Fc technology to three additional antibodies. Omeros is responsible for all development and commercialization activities. We received an upfront payment of $5.0 million, and for each product incorporating our Xtend Fc technology, we are eligible to receive up to $65.0 million in milestones, which includes $15.0 million in development milestones, $25.0 million in regulatory milestones and $25.0 million in sales milestones. We are also eligible to receive royalties in the mid-single digit percentage range on net sales of approved products.
Viridian Therapeutics, Inc./MiRagen Therapeutics, Inc.
In December 2020, we entered into an agreement with MiRagen Therapeutics, Inc., in which we provided MiRagen a non-exclusive license to our Xtend Fc technology and an exclusive license to apply our Xtend Fc technology to antibodies targeting IGF-1R. MiRagen subsequently changed its name to Viridian Therapeutics, Inc. Viridian is responsible for all development and commercialization activities. We received an upfront payment of 322,407 shares of Viridian common stock valued at $6.0 million and are eligible to receive up to $55.0 million in milestones, which include $10.0 million in development milestones, $20.0 million in milestone payments from this partnershipregulatory milestones and to date we have received a cumulative total of $37.5$25.0 million in milestonesales milestones. We are also eligible to receive royalties in the mid-single digit percentage range on net sales of approved products.
Catabasis Pharmaceuticals, Inc./Quellis Biosciences, Inc.
In May 2018, we entered into an agreement with Quellis Biosciences, Inc., in which we provided Quellis a non-exclusive license to our Xtend Fc technology to apply to an identified antibody. Quellis is responsible for all development and upfront payments.commercialization activities. We received an equity interest in Quellis, and in January 2021, upon Quellis merging into Catabasis Pharmaceuticals, Inc., we received common and preferred shares of Catabasis stock in exchange for our equity in Quellis. We are eligible to receive up to an additional $38.0$66.0 million in regulatory and sales milestones, and royalties on the sale of approved products in the low single-digit percent range.
MorphoSys
In June 2011 we entered into a collaboration and license agreement (the MorphoSys Agreement) with MorphoSys AG (MorphoSys) to license the worldwide rights to XmAb5574 (now known as MOR208). MOR208 is an antibody drug candidate originally developed by us and it incorporates our XmAb cytotoxic Fc domain.
12
MorphoSys is currently conducting Phase 3 clinical trials of MOR208 in patients with non-Hodgkin lymphomas (NHL) and a Phase 2 clinical trial in chronic lymphocytic leukemia (CLL). MorphoSys has indicated that it has received Breakthrough Therapy designation from the FDA for targeting diffuse large B-cell lymphoma (DLBCL) in combination with lenalidomide. MorphoSys has indicated it will be submitting MOR208 for regulatory approval in 2019.
We have received a total of $28.5 million in upfront and milestone payments under the MorphoSys Agreement and we are eligible to receive additional milestones for development of the MorphoSys compounds in oncology and additional milestones for development of compounds in different indications. Total additional milestones for MorphoSys compounds currently in development total $111 million which include: $6include $6.0 million in development milestones, $55$30.0 million in regulatory milestones and $50$30.0 million of aggregate milestone payments for the achievement of certain productin sales goals. If licensed productsmilestones. We are commercialized, we are entitledalso eligible to receive tiered royalties in the high single‑mid-single digit percentage range on net sales of approved products.
Strategic Collaborations
We enter into strategic collaborations where we can create synergies between our partners' capabilities and assets and our own protein engineering capabilities, XmAb technologies and XmAb drug candidates. Through these arrangements we seek to low‑double digit percent range.create new drug candidates, investigate novel combination therapies and potentially identify additional indications for our portfolio of XmAb drug candidates.
15
MorphoSys AG
The term of this agreement will continue until all of MorphoSys’ royalty payment obligations have expired unless terminated earlier.
CSL
In February 2009,November 2020, we entered into a research license and commercialization agreement (CSL Agreement) with CSL Limited (CSL) in which we provided CSL with a research license to our cytotoxic Fc technology and options to non-exclusive commercial licenses. CSL elected to exercise one commercial license for a compound, CSL362.
In 2013 CSL sublicensed CSL362 to Janssen Biotech Inc. (Janssen Biotech). In August 2015, CSL, through its sublicensee, Janssen Biotech, initiated a Phase 2 clinical trial for CSL362. In March 2017, Janssen Biotech initiated a Phase 3 trial for CSL362 and we received a milestone payment of $3.5 million. In July 2017, Janssen discontinued the Phase 3 trial for CSL362 and returned the compound to CSL.
Boehringer Ingelheim
In February 2007, we entered into a research and option agreement (BI Agreement) with Boehringer Ingelheim International GmbH (BI). Under the terms of the BI Agreement we provided a research license to our XmAb cytotoxic technology and options to non-commercial licenses. BI elected to take options to two licenses and there is currently one compound in a Phase 1 clinical trial.
NIH
In January 2016, we announced that the National Institutes of Health (NIH) initiated a Phase 1 clinical trial of VRC01LS, a therapeutic antibody for the treatment of human immunodeficiency virus (HIV) that uses our Xtend technology to enhance antibody half-life. VRC01LS is a humanized monoclonal antibody targeted to the CD4 binding site of HIV-1. VRC01LS is a modification of the VRC01 monoclonal antibody, which demonstrated a suppression of HIV viral load in a Phase 1 trial conducted by NIH. NIH has not entered into an agreement with usMorphoSys AG to conduct clinical studies to investigate the combination of plamotamab and tafasitamab in combination with lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), first-line DLBCL, and relapsed or refractory follicular lymphoma (FL). MorphoSys and Incyte Corporation will provide tafasitamab for this technology.the studies, which Xencor will sponsor and fund. We plan to initiate a Phase 1/2 study evaluating the combination in patients with relapsed or refractory DLBCL in the second half of 2021.
Atreca, Inc.
13
costs and profits. Each company has the option to lead development, regulatory and commercialization activities for one of the joint programs. In addition, each partner has the option to pursue up to two programs independently, with a royalty in the mid- to high-single digit percentage range payable on net sales to the other partner.
Our StrategyThe University of Texas MD Anderson Cancer Center
Our goal isIn September 2020, we entered into an agreement with MD Anderson, in which we will provide funding over a five-year period, and MD Anderson will collaborate to becomedesign and execute additional clinical studies with our portfolio of XmAb drug candidates, including novel bispecific antibody and cytokine candidates. We own all rights to the programs and results generated from these studies.
In December 2020, we entered into a leading biopharmaceutical company focused on developingsecond agreement with MD Anderson to develop novel CD3 bispecific antibody therapeutics for the potential treatment of patients with cancer. MD Anderson will work to identify and commercializing engineered monoclonaldevelop potential antibodies, and other proteins in oncologywe will apply its our Fc bispecific technology to treat patients with severecreate therapeutic candidates. MD Anderson will then conduct and life-threatening diseases with unmet medical needs. Key elements of our strategy are to:fund all preclinical activities to advance candidates toward clinical studies. We have certain exclusive options to license worldwide rights to develop and commercialize potential new medicines arising from the collaboration.
|
|
|
|
|
|
|
|
|
|
Our Research and Development Pipeline
We have used our XmAb Fc platforms and antibody optimizationprotein engineering capabilities to produce a growing pipeline of drug candidates in clinical and preclinical development. These include multiple oncology candidates using our bispecific Fc domain, including CD3 candidates, TME activator checkpoint,bispecific antibody and cytokine candidates, and drug candidates using our immune inhibitor Fc domain.candidates. We will continue to progressadvance these candidates as additional options for clinical development by us or as out‑licensingout-licensing opportunities. We also from time to time in-license antibody technologies and compounds from other companies which we believe may allow us to create potential product candidates by incorporating our XmAb technology. These licenses may require us to pay up-frontupfront fees, development and commercial milestone payments, and if commercial products are approved, royalties on net sales.
Human Capital Management
Our Employees and Commitment to Diversity, Equity, and Inclusion
Our ability to develop XmAb technologies, advance our programs into late-stage development, position our programs for commercialization and identify successful business partnerships is dependent on attracting, retaining, and developing our employees. We seek and support a diverse population of employees without regard to race, gender or sexual orientation. As of December 31, 2020, we had 202 full-time employees, representing a 22% increase in our employee workforce as compared to December 31, 2019. Of these, 156 were engaged in research and development
1416
activities, and 46 are engaged in business development, information systems, facilities, human resources or administrative support. Of these employees, 42 hold Ph.D. degrees, and 6 hold M.D. degrees. None of our employees are represented by any collective bargaining unit. We believe we maintain good relations with our employees.
We are an equal opportunity employer and maintain policies that prohibit unlawful discrimination based on race, color, religion, gender, sexual orientation, gender identity/expression, national origin/ancestry, age, disability, marital and veteran status. We are proud to employ a diverse workforce that, as December 31, 2020, was 53% non-white and 55% women. In addition, as of December 31, 2020, women made up 22% of our senior leadership team. We strive to build and nurture a culture where all employees feel empowered to be their authentic selves.
We seek to provide human capital policies that provide for the health, safety and welfare of our employees as well as professional development and training. In 2020 in connection with the ongoing pandemic we implemented the following policies:
| ● | Instituted a remote work mandate for all non-laboratory staff and provided technical support and training to enable employees to continue to perform their responsibilities while working remotely; |
| ● | Implemented onsite safety procedures for all laboratory staff which includes mandatory weekly onsite SARS-CoV-2 virus testing for all laboratory employees and their household members, reimbursement of 100% of medical insurance costs for all onsite employees, and fully paid time off for any employee that missed time due to the COVID-19 virus including for the care of family members; and |
| ● | Provided additional compensation for onsite employees and provided additional days off for all employees. |
We provide compensation packages designed to attract and retain high-quality employees, and all of our employees are eligible for cash bonuses and grants of equity awards. We regularly evaluate our compensation programs with an independent compensation consultant and utilize industry benchmarking in an effort to ensure they are competitive compared to similar biotechnology and biopharmaceutical companies with which we compete for talent and that they are fair and equitable across our workforce with respect to gender, race, and other personal characteristics. In addition, we provide a variety of programs and services to help employees meet and balance their needs at work, at home and in life, including an attractive mix of healthcare, insurance, and other benefit plans. We deliver a benefits program that is designed to keep our employees and their families healthy, which includes not only medical, dental and vision benefits, but also dependent care, mental health, and other wellness benefits.
| ● | We also value career development for all employees, and we provide reimbursement and time for employees to attend professional development courses ranging from technical training, competency-based workshops and leadership development programs facilitated by external partners who are experts in their respective fields. Direct managers also take an active role in identifying individualized development plans to assist their employees in realizing their full potential and creating opportunities for promotions and added responsibilities that enhance the engagement and retention of our workforce. |
Market Opportunity
Our drug candidates that use the XmAb bispecific Fc domain, including XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104,plamotamab, XmAb717, vibecotamab, tidutamab, XmAb841, XmAb104 and XmAb24306XmAb306: We are pursuing the development ofdeveloping our bispecific Fcantibody and cytokine candidates for applications in oncology, whereby the immune system is modulated to treat cancer. Cancer is a broad group of diseases in which cells divide and grow in an uncontrolled fashion, forming malignancies that can invade other parts of the body, and it is the second leading cause of death in the United States (U.S.). The American Cancer Society estimates that in 20182021 there werewill be approximately 1.71.9 million new cases of cancer and approximately 609,000608,570 deaths from cancer. The National Institutes of Health (NIH) estimatesestimated that based on growth and aging of the U.S. population, medical expenditures for cancer in the year 2020 arewere projected to reach at least $158$158.0 billion (in 2010 dollars).
XmAb5871: We have advanced development17
XmAb7195: The potential indication for which we are currently pursuing XmAb7195 development is allergic asthma. According to the Centers for Disease Control and Prevention, asthma affects approximately one in 12 Americans. More than half of asthma sufferers have at least one attack each year and thousands of people die from asthma attacks each year. Disease severities cover a wide range, and the treatment landscape is multi-tiered for asthma patients. Patients with mild and moderate asthma are generally well controlled with inhaled corticosteroids and long-acting beta agonists. However, a small percentage of the estimated 25 million asthma patients in the U.S. have severe asthma and are refractory to high-dose combination therapy. This severe population is commonly treated with oral corticosteroids, which are associated with many undesirable side effects and are often insufficient to control the disease.
Intellectual Property
The foundation for our XmAb technology and our product candidates and partnering is the generation and protection of intellectual property for novel antibody and cytokine therapeutics. We combine proprietary computational methods for amino acid sequence design with laboratory generation and testing of new antibody and cytokine compositions. Our design and engineering team prospectively assesses, with patent counsel, the competitive landscape with the goal of building broad patent positions and avoiding third-party intellectual property.
As a pioneer in Fc domain engineering, we systematically scanned the structure of the Fc domain to discover Fc variants. We have filed patent applications relating to thousands of specific Fc domain variants with experimental data on specific improvements of immune function, pharmacokinetics, structural stability, and novel structural constructs. We have filed additional patent applications derived from these applications as we discover new properties of the Fc variants and as new business opportunities arise. We continually seek to expand the intellectual property coverage of our technology and candidates and invest in discovering new Fc domain technologies, antibody product candidates, and antibodycytokine product candidates.
Our patent estate, on a worldwide basis, includes over 7501,000 issued patents and pending patent applications which we own, or for which we have a fully-paid exclusive license, with claims directed to XmAb Fc domains, all of our clinical and preclinical stage antibodiesproduct candidates and our computational protein design methods and platforms. We also have a large number of issued patents and pending patent applications with claims directed specifically to our XmAb technology and candidates.
15
The patent expiration in the U.S. and major foreign countries (ex-U.S.) for our key technologies and drug candidates is:is set forth below. We have pending applications filed that may extend the exclusivity of some of our technology and products:
| | |
Technology | | Patent Expiry |
Cytotoxic | | 2025 U.S.; |
Immune Inhibitor |
|
|
Xtend | | 2025 U.S.; 2028 |
Bispecific |
| |
|
| |
|
| |
|
| |
|
| |
|
| 2034 U.S. and Ex-U.S. |
| | 2035 U.S. and Ex-U.S. |
CD28 T Cell Engagers | | 2040 U.S. and Ex-U.S. |
| | |
Company Products | | Patent Expiry |
Obexelimab (XmAb5871) | | 2029 U.S.; 2028 Ex-U.S. |
Plamotamab | | 2035 U.S. and Ex-U.S. |
Vibecotamab | | 2035 U.S.; 2036 Ex-U.S. |
Tidutamab | | 2037 U.S. and Ex-U.S. |
|
| |
| | 2037 U.S. and Ex-U.S. |
XmAb564 | | 2038 U.S. and Ex-U.S. |
XmAb819 | | 2040 U.S. and Ex-U.S. |
XmAb306 | | 2038 U.S.; 2037 Ex-U.S. |
| | |
Partnered Products | | Patent Expiry |
Monjuvi (tafasitamab) | | 2029 U.S.; 2027 Ex-U.S. |
Ultomiris | | 2025 U.S.; 2028 Ex-U.S. |
AIMab7195 (XmAb7195) | | 2029 U.S. and Ex-U.S. |
18
The Hatch-Waxman Act permits a patent term extension for FDA-approved drugs, including biological products, 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 drug is under regulatory review. Patent extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only one patent applicable to an approved drug may be extended. Similar provisions are available in Europe and other jurisdictions to extend the term of a patent that covers an approved drug. In the future, if and when our pharmaceutical product candidates receive FDA approval, we expect to apply for patent term extensions on patents covering those products. We intend to seek patent term extensions to any of our issued patents in any jurisdiction where these are available, however there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of whether such extensions should be granted, and even if granted, the length of such extensions.
The Patient Protection and Affordable Care Act, as amended by the Healthcare and Education Affordability Reconciliation Act (collectively the ACA) created a regulatory scheme authorizing the FDA to approve biosimilars via an abbreviated licensure pathway. In many cases, this allows biosimilars to be brought to market without conducting the full suite of clinical trials typically required of originators. Under the ACA, a manufacturer may submit an application for licensure of a biologic product that is "biosimilar to" or "interchangeable with" a previously approved biological product or "reference product." The "biosimilar" application must include specific information demonstrating biosimilarity based on data derived from: (1) analytical studies, (2) animal studies, and (3) a clinical study or studies that are sufficient to demonstrate safety, purity, and potency in one or more appropriate conditions of use for which the reference product is licensed, except that FDA may waive some of these requirements for a given application. Under this new statutory scheme, an application for a biosimilar product may not be submitted to the FDA until four years after the date of first licensure. The FDA may not approve a biosimilar product until 12 years from the date on which the reference product was first licensed. The law does not change the duration of patents granted on biological products. Even if a product is considered to be a reference product eligible for exclusivity, another company could market a competing version of that product if the FDA approves a full Biologics License Application (BLA) for such product containing the sponsor's own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity, and potency of their product. There have been recent proposals to repeal or modify the ACA and it is uncertain how any of those proposals, if approved, would affect these provisions.
In addition to patent protection, we rely on trade secret protection and know-how to expand our proprietary position around our technology and other discoveries and inventions that we consider important to our business. We seek to protect this intellectual property in part by entering into confidentiality agreements with our employees, consultants, scientific advisors, clinical investigators, and other contractors and also by requiring our employees, commercial contractors, and certain consultants and investigators, to enter into invention assignment agreements that grant us ownership of certain discoveries or inventions made by them.
Further, we seek trademark protection in the United States and in certain other jurisdictions where available and when we deem appropriate. We have obtained registrations for the Xencor trademark, as well as certain other trademarks, which we use in connection with our pharmaceutical research and development services and our clinical-stage products, including XmAb, PDA, and Protein Design Automation.Automation, Proteins By Design and Antibodies By Design. We currently have registrations for Xencor and PDA in the United States, Australia, Canada, the European Community, and Japan, for Protein Design Automation in the United States, Australia, Canada and the European Community, and for XmAb in the United States, Australia, andCanada, the European Community.Community and Japan.
ManufacturingThird Party Vendors and Suppliers
Our internal research activities are focused on early research stage and preclinical activities and studies. We rely on third party vendors, suppliers and contractors for all other research, development and clinical activities. We are able to internally manufacture the quantities of our product candidates required for relatively short preclinical animal studies. We believe that this allows us to accelerate the drug development process by not having to relyrelying on third parties for all of our manufacturing needs. We have adopted a manufacturing strategy of contracting with third parties in accordance with current good manufacturing practices (cGMPs) for the manufacture of drug substance and product, including our pipeline of bispecific antibody and cytokine development candidates and also our XmAb5871 and XmAb7195obexelimab development candidates.candidate. We have used third party manufacturers for all our bispecific Fcantibody and cytokine candidates which include: XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104,
19
vibecotamab, plamotamab, tidutamab, XmAb717, XmAb841, XmAb104, XmAb306, and XmAb24306.XmAb564. Additional contract manufacturers are used to fill, label, package and distribute investigational drug products. This allows us to maintain a more flexible infrastructure while focusing our expertise on developing our products. XmAb5871 and XmAb7195 areObexelimab is produced by mammalian cell culture of a Chinese hamster ovary cell line that expresses the antibody, followed by multiple purification and filtration steps typical of those used for monoclonal antibodies. We do not have any long-term manufacturing agreements in place and will ultimately depend on contract manufacturers for the manufacture of our products for commercial sale, as well as for process development. We have successfully completed clinical trials with subcutaneous formulations for both XmAb5871 and XmAb7195obexelimab which have been manufactured with third party contract manufacturers. In February 2020, we entered into a License, Development and Commercialization Agreement for XmAb7195 (Aimmune Agreement) with Aimmune Therapeutics, Inc. (Aimmune). Under the Aimmune Agreement, Aimmune will assume all future manufacturing of XmAb7195.
16
KBI Biopharma, Inc.
In July 2014, we entered into a master services agreement (KBI Agreement) with KBI Biopharma, Inc. (KBI). We have engaged KBI under the KBI Agreement for process development, clinical scale-up, analytical method development, formulation development, and other services related to drug substance and drug product for our bispecific antibody and cytokine development candidates: XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104,vibecotamab, plamotamab, tidutamab, XmAb717, XmAb841, XmAb104, XmAb306, and XmAb24306XmAb564 in accordance with cGMP regulations. For each bispecific program, we have entered into a separate agreement with the terms and conditions of services and payment. The KBI Agreement is for a three-year term but is automatically extended on an annual basis until the services are completed. The KBI Agreement may be terminated by either party for a breach that is not remedied within 30 days after notice or 60 days after notice of the existence of an incurable scientific or technical issue that renders KBI unable to render services under the KBI Agreement, by after 60 day60-day notice, or in the event of a bankruptcy of a party. For termination other than a material breach by KBI, we must pay for all services conducted prior to the termination and to wind down the activities.
Cell Line Agreements with Selexis
In December 2015, we entered into a master service agreement (Selexis Agreement) with Selexis SA (Selexis) for the manufacture of Selexis cell lines. Under the terms of the Selexis Agreement, Selexis will manufacture cell lines for the antibody candidates provided by us and upon completion of the cell lines, we have the option to take an unrestricted commercial license to the cell line. The terms of each commercial license require us to make payments upon achievement of certain development and regulatory milestones and we will also pay royalties based on a percentage of net sales for products that are derived from or utilize the Selexis cell line. The royalty percentage is less than 1%.
Selexis has manufactured cell lines for all our bispecific Fcantibody and cytokine drug candidates, and we currently have commercial licenses to the Selexis cell line for the following bispecific Fcantibody and cytokine candidates: XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104,vibecotamab, plamotamab, tidutamab, XmAb717, XmAb841, XmAb104, XmAb306 and XmAb24306.XmAb564.
License Agreements with BIO-TECHNE
In February 2015, we entered into a license agreement with BIO-TECHNE Corporation (BIO-TECHNE) for a non-exclusive license to certain antibody technology including monoclonal antibodies which recognize human somatostatin reception 2.receptor 2 (SSTR2). The variable domain of this antibody is incorporated in our XmAb18087tidutamab drug candidate.
Under the terms of this agreement, we made an upfront payment and are obligated to make payments upon the achievement of certain development and regulatory milestones, and royalties based on a percentage of net sales from products that are derived from the XmAb18087tidutamab program. The royalty percentage is less than 1%.
We entered into a second agreement with BIO-TECHNE effective February 2018 for a non-exclusive license to a certain recombinant monoclonal antibody reactive with human programmed death protein, PD-1 antibody. We expect to use this protein in certain of our oncology drug candidates.
Under the terms of this agreement, we made an upfront payment and are obligated to make payments upon the achievement of certain development, regulatory and sales milestones, and royalties based on a percentage of net sales from products that are derived from the PD-1 antibody. The royalty percent is 1%.
20
Umbrella Development and Manufacturing and Cell Line Sale AgreementsServices Agreement with CatalentPatheon Biologics LLC
In September 2005,2018, we entered into a development and manufacturing services agreement (the Catalent Manufacturingan Umbrella Development Services Agreement (Patheon Agreement) with Catalent Pharma SolutionsPatheon Biologics LLC (Catalent)(Patheon). Under the terms of the agreement, Catalent will, from time to time, provide development and manufacturing services for us.
17
We have also entered into separate cell line sale agreements (Cell Line Agreements) with Catalent for the XmAb5871 and XmAb7195 cell lines. Catalent manufactured the cell lines for the XmAb5871 and XmAb7195 programs using their proprietary GPEx® technology. Under the Catalent ManufacturingPatheon Agreement, we have an unrestricted license to the GPEx cell lines provided that Catalent is manufacturing drug substance material from the cell line. The Cell Line Agreements allow us to transfer the manufacturing processes for either XmAb5871 or XmAb7195 to a third party manufacturer. In 2018, we transferred the manufacturing process for XmAb5871 from Catalent to a third party manufacturer.
Upon transferany of the XmAb5817 or XmAb7195 cell line to a third party manufacturer, we will be required to make payments to Catalent based uponaffiliates within the achievementglobal network of certain development and regulatory milestones and will also pay royalties based on a percentage of net sales for products that are derived from or utilize the GPEx cell line. The royalty percentages under each Cell Line Agreement are less than 1.0%. In 2017, we transferred the cell line for XmAb5871 to a third party manufacturer. We have not made any payments under the Cell Line Agreement to date.
We have the unilateral right to terminate the Catalent Manufacturing Agreement upon 30 days written notice to Catalent. Absent early termination, the agreement will remainservice sites in effect. If we terminate the agreement without cause or if Catalent terminates the agreement for our material breach of the agreement, our ownership rights in the cell line will automatically terminate, and title will revert to Catalent.
Master BioprocessingThermo Fisher Scientific Inc.’s Pharma Services Agreement with FUJIFILM Diosynth Biotechnologies
In June 2017, we entered into a bioprocessing services agreement (FUJI Agreement) with FUJIFILM Diosynth Biotechnologies U.S.A. (FUJI). We have engaged FUJI under the FUJI Agreement forGroup may perform clinical manufacturing and development services related to drug substance for our XmAb5871 programus in accordance with cGMP regulations. The FUJIPatheon Agreement includes a statement of work for Patheon to provide process transfer, process development and cGMP manufacturing to support our obexelimab program. The Patheon Agreement may be terminated by either party for a breach or default that is not remedied within 4530 days, or forsuch other time period as may be reasonably necessary to remedy such breach after receiving notice of the breach from the non-breaching party or if the other party is subject to an additional 45 days if such cure has commenced by the responsible party but it is unable to cure it within the original 45-day notice period. If such cure is not completed within the 90-day period, we have the right to terminate the FUJI Agreement.insolvency event. We have the unilateral right to terminate the Patheon Agreement upon 30 days written notice to FUJI.Patheon for any business reason, subject to cancellation fees. Patheon has the unilateral right to terminate the Patheon Agreement if we request to reschedule work beyond 120 days, the project work is not progressing according to our expectations and we cannot agree on appropriate changes, after six months of inactivity on a project at our request or if Patheon determines it is unable to perform its obligations in a safe and effective way in compliance with applicable regulatory requirements.
Patheon is currently conducting process transfer, process development and cGMP manufacturing for our obexelimab program and process development and cGMP manufacturing for our XmAb819 program.
Competition
We compete in an industry that is characterized by rapidly advancing technologies, intense competition, and a strong emphasis on proprietary products. Our competitors include pharmaceutical companies, biotechnology companies, academic institutions, and other research organizations. We compete with these parties for promising targets for antibody‑basedantibody-based therapeutics, new technology for optimizing antibodies and cytokines, and in recruiting highly qualified personnel. Many competitors and potential competitors have substantially greater scientific, research, and product development capabilities as well as greater financial, marketing and sales, and human resources than we do. In addition, many specialized biotechnology firms have formed collaborations with large, established companies to support the research, development, and commercialization of products that may be competitive with ours. Accordingly, our competitors may be more successful than we may be in developing, commercializing, and achieving widespread market acceptance. In addition, our competitors’ products may be more effective, more effectively developed, or more effectively marketed and sold than any treatment we or our development partners may commercialize, andwhich may render our product candidates obsolete or noncompetitive before we can recover the expenses related to developing and commercializing any of our product candidates.
Competition in the field of cancer drug development is intense, with more than 250hundreds of compounds in clinical trials bytrials. Many large multinational pharmaceutical companies. Wecompanies and other smaller biotechnology companies are aware of companies withdeveloping competing bispecific technologiesantibody platforms, and many of these companies have advanced multiple drug candidates into clinical development, including Amgen MacroGenics, Inc. (MacroGenics),; Genmab A/S; Macrogenics, Inc.; Merus Inc.,N.V.; Regeneron Pharmaceuticals, Inc., F. Hoffmann-LaRoche Ltd. (Roche), Genentech,; Roche Holding AG; and Zymeworks Inc. Several
We are developing bispecific antibody drug candidates engineered to direct cytotoxic T cell killing of tumor cells, by engaging the CD3 receptor on T cells and an antigen on tumor cells. Regarding plamotamab, other companies have competing bispecific molecules as both Roche and Regeneron have CD20 x CD 3 candidates in Phase 1 development and MacroGenics has a CD123 xdeveloping CD3 bispecific antibodies directed to CD20, an antigen expressed on many blood tumors, include AbbVie Inc. and Genmab A/S; IGM Biosciences, Inc.; Regeneron Pharmaceuticals, Inc.; and Roche Holding AG. Other antibodies, antibody drug candidates and cell therapies are in clinical development . Theor approved to treat patients with non-Hodgkin lymphomas. Regarding vibecotamab, other companies developing CD3 bispecific antibodies directed to CD123, an antigen expressed on myeloid tumors, include Aptevo Therapeutics Inc. and Macrogenics, Inc.
We are also developing several bispecific antibody drug candidates engineered to selectively engage the immune system in order to treat patients with cancer, such as XmAb717, XmAb841 and XmAb104. Immuno-oncology is a competitive field of oncology has multiplewithin the biotechnology and pharmaceutical industries, and most large pharmaceutical companies with competing oncology programs including Bristol Myers-Squib,are developing drug candidates, have marketed medicines in this space, or both: AstraZeneca plc; Bristol-Myers Squibb Company; GlaxoSmithKline plc; Merck & Co., Inc.; Novartis AG; Pfizer Inc.; Roche Holding AG; and Roche. Sanofi S.A.
21
While tuning the binding affinities plays a crucial role in designing the mechanism of action for this class of bispecific antibody, smaller companies advancing clinical programs that, like XmAb717, dually target the immune checkpoint receptors PD-1 and CTLA-4 include Akeso, Inc. and Macrogenics, Inc.
Several companies are developing engineered cytokines intended to activate specific immune cell populations in order to treat patients with cancer and/or autoimmune diseases, including Alkermes plc; Amgen Inc.; Cue Biopharma, Inc.; Cytune Pharma; Eli Lilly and Company; IGM Biosciences, Inc.; ImmunityBio, Inc.; Kadmon Holdings, Inc.; Medicenna Therapeutics Corp.; Nektar Therapeutics, Inc.; Neoleukin Therapeutics, Inc.; Novartis AG; Pandion Therapeutics, Inc.; Roche Holding AG; Sanofi S.A.; Sutro Biopharma, Inc.; and Xilio Therapeutics, Inc.
In addition, we are aware of a number of other companies with development stage programs that may compete with the drug candidates we and our licensees are developing in the future. We anticipate that we will face intense and increasing competition as new treatments enter the market and advanced technologies become available.
18
Regulatory Overview
Our business and operations are subject to a variety of U.S. federal, state and local and foreign supranational, national, provincial and municipal laws, regulations and trade practices. The FDA and comparable regulatory authorities in state and local jurisdictions and in other countries impose substantial and burdensome requirements upon companies involved in the clinical development, manufacture, marketing, and distribution of drugs and biologics. These agencies and other federal, state and local entities regulate research and development activities and the testing, manufacture, quality control, safety, effectiveness, labeling, storage, recordkeeping, approval, advertising and promotion, and export and import of our product candidates.
U.S. Government Regulation
We are subject to extensive regulation by the U.S. and other countries. Regulation by government authorities is a significant factor in the development, manufacture, distribution and ongoing research activities. All our products in development will require regulatory approval by government agencies prior to commercialization. In particular, drugs and biologic products are subject to rigorous preclinical studies and clinical trials and other approval procedures of the FDA and similar regulatory authorities in foreign countries. The process of obtaining these approvals and the subsequent compliance with appropriate federal and state statutes and regulations require the expenditure of substantial time and financial resources. Various federal and state statutes and regulation also govern or influence testing, manufacturing, safety, labeling, storage, tracking, tracing and record-keeping of drugs and biologic products and their marketing.
U.S. Drug Development Process
In the United States, the FDA regulates drugs and biologic products under the Federal Food, Drug and Cosmetic Act (FDCA), its implementing regulations, and other laws including, in the case of biologics, the Public Health Service Act. Our antibody product candidates are subject to regulation by the FDA as a biologic. Biologics require the submission of a Biologics License Application (BLA)BLA to the FDA and approval of the BLA by the FDA before marketing in the United States. The process of obtaining regulatory approvals for commercial sale and distribution and the subsequent compliance with applicable federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources. Failure to comply with the applicable requirements at any time during the product development process, approval process or after approval, may subject an applicant to administrative or judicial civil or criminal sanctions. These sanctions could include the FDA’s refusal to approve pending applications, license suspension or revocation, withdrawal of an approval, imposition of a clinical hold on clinical trials, warning letters, product recalls, product seizures, total or partial suspension of production, or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement or civil and/or criminal penalties. The process required by the FDA before a biologic may be marketed in the United States generally involves the following:
1. | completion of preclinical laboratory tests, animal studies, and formulation studies performed in accordance with the FDA’s current Good Laboratory Practices (GLP) regulations; |
22
2. | submission to and acceptance by the FDA of an IND which must become effective before human clinical trials in the United States may begin; |
3. | performance of adequate and |
4. | submission to and acceptance by the FDA of a BLA; |
5. | satisfactory completion of an FDA inspection (if the FDA deems it as a requirement) of the manufacturing facility or facilities where the product is produced to assess compliance with the FDA’s cGMP regulations to assure that the facilities, methods, and controls are adequate to preserve the product’s identity, strength, quality, and purity; |
6. | potential audits by the FDA of the nonclinical and clinical trial sites that generated the data in support of the BLA; |
7. | potential review of the BLA by an external Advisory Committee to the FDA, whose recommendations are not binding on the FDA; and |
8. | FDA review and approval of the BLA prior to any commercial marketing or sale. |
19
Before testing any compounds with potential therapeutic value in humans, the product candidate enters the preclinical testing stage. Preclinical tests include laboratory evaluations of product chemistry, stability, and formulation, as well as animal studies to assess the potential toxicity and activity of the product candidate. Clinical trials involve the administration of the product candidate to human patients under the supervision of qualified investigators, generally physicians not employed by or under the clinical trial sponsor’s control. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria, and the parameters to be used to monitor subject safety and effectiveness. The FDA or responsible Institutional Review Board may place a trial on hold at any time related to perceived risks to patient safety. Phases of clinical development include:
1. | Phase 1. The product candidate is initially introduced into a limited population of healthy human subjects, or in some cases, patients with the disease for which the drug candidate is intended, and tested for safety, dosage tolerance, absorption, metabolism, distribution, and excretion. In the case of some products for some diseases, or when the product may be too inherently toxic to ethically administer to healthy volunteers, the initial human testing is often conducted in patients with the disease or condition for which the product candidate is intended to gain an early indication of its effectiveness. |
2. | Phase 2. The product candidate is evaluated in a limited patient population (but larger than in Phase 1) to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted indications, and to assess dosage tolerance, optimal dosage, and dosing schedule. |
3. | Phase 3. Clinical trials are undertaken to further evaluate dosage and provide substantial evidence of clinical efficacy and safety in an expanded patient population (such as several hundred to several thousand) at geographically dispersed clinical trial sites. Phase 3 clinical trials are intended to establish the overall risk/benefit ratio of the product and provide an adequate basis for product labeling. Generally, two adequate and |
| 4. | Post Approval. Clinical trials or other post-approval commitments may be conducted after initial marketing approval. These studies are used to gain additional experience from the treatment of patients in the intended therapeutic indication and may be required by the FDA as a condition of approval. |
23
Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the biologic and finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.
U.S. Review and Approval Processes
The results of product development, preclinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests, proposed labeling, and other relevant information are submitted to the FDA in the form of a BLA requesting approval to market the product for one or more specified indications. The standard time for the FDA to accept a BLA filingsubmission is two months.
If the FDA determines that the BLA is substantially complete, it will accept the BLA for filing. review.
Once accepted, for filing, the FDA reviews the BLA to determine, among other things, whether the proposed product is safe and effective for its intended use, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity, strength, quality, and purity, and it may inspect the manufacturing facilities to assure cGMP compliance and clinical sites used during the clinical trials to assure cGMP compliance. The standard FDA review process is 10 months once a BLA is accepted for review, but it can take longer. During the review process, the FDA also will determine whether a risk evaluation and mitigation strategy (REMS) is necessary to assure the safe use of the product. If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS prior to approval. A REMS can substantially increase the costs of obtaining approval. In addition, under the Pediatric Research Equity Act, a BLA or supplement to a BLA 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.
20
The FDA will issue a complete response letter describing deficiencies in the BLA and recommend actions if the agency decides not to approve the BLA. The applicant will have to address all of the deficiencies which could take substantial time to address.
If the product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages, or the indications for use may otherwise be limited and may require that certain contraindications, warnings, or precautions be included in the product labeling. In addition, the FDA may require post marketing studies, sometimes referred to as Phase 4 testing, which involves clinical trials designed to further assess drug safety and effectiveness and may require testing and surveillance programs to monitor the safety of approved products that have been commercialized.
Post‑ApprovalPost-Approval Requirements
Any biologic products for which we or our collaborators receive FDA approvals are subject to continuing regulation by the FDA, including, among other things, cGMP compliance for product manufacture, record‑keepingrecord-keeping requirements, reporting of adverse experiences with the product, providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, complying with certain electronic records and signature requirements, and complying with FDA promotion and advertising requirements, which include, among others, restrictions on direct‑to‑consumerdirect-to-consumer advertising, promoting biologics for uses or in patient populations that are not described in the product’s approved labeling (known as “off‑label“off-label use”), industry‑sponsoredindustry-sponsored scientific and educational activities, and promotional activities involving the internet. Failure to comply with these or other FDA requirements can subject a manufacturer to possible legal or regulatory action, such as product reclass, warning letters, suspension of manufacturing, seizure of product, injunctive action, mandated corrective advertising or communications with healthcare professionals, possible civil or criminal penalties, or other negative consequences, including adverse publicity.
24
U.S. Patent Term Restoration and Marketing Exclusivity
Depending upon the timing, duration and specifics of the FDA approval of any of our biologic product candidates, we may apply for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Amendments. The Hatch‑WaxmanHatch-Waxman Amendments permit a patent restoration term of up to five years for one patent per product as compensation for patent term lost during product development and the FDA regulatory review process of that product. The U.S. Patent and Trademark Office, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.
Market exclusivity provisions under the FDCA can also delay the submission or the approval of certain applications of other companies seeking to reference another company’s BLA. Specifically, the Biologics Price Competition and Innovation Act established an abbreviated pathway for the approval of biosimilar and interchangeable biological products generally not earlier than 12 years after the original BLA approval. The abbreviated regulatory pathway establishes legal authority for the FDA to review and approve biosimilar biologics, including the possible designation of a biosimilar as “interchangeable” based on their similarity to existing brand product.
U.S. Foreign Corrupt Practices Act
The U.S. Foreign Corrupt Practices Act, to which we are subject, prohibits corporations and individuals from engaging in certain activities to obtain or retain business or to influence a person working in an official capacity. It is illegal to pay, offer to pay or authorize the payment of anything of value to any foreign government official, government staff member, political party or political candidate in an attempt to obtain or retain business or to otherwise influence a person working in an official capacity.
21
Pharmaceutical Coverage, Pricing and Reimbursement
The cost of pharmaceuticals continues to generate substantial governmental and third‑partythird-party payor interest. We expect that the pharmaceutical industry will experience pricing pressures due to the trend toward managed healthcare, the increasing influence of managed care organizations and additional legislative proposals. Significant uncertainty exists and will continue to exist as to the coverage and reimbursement status of any product candidate for which we obtain regulatory approval. In the United States and markets in other countries, sales of any product for which we receive regulatory approval for commercial sale will depend in part on the availability of coverage and adequate reimbursement from third-party payors. Third-party payors include government payor programs at the federal and state levels, including Medicare and Medicaid, managed care providers, private health insurers and other organizations. Third‑party payors are increasingly challenging the price and examining the medical necessity and cost‑effectiveness of medical products and services, in addition to their safety and efficacy. Formulary placement by third-party payors is very competitive and can lead to lower prices and may effectively restrict patient access to our drugs. 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 the FDA approvals. Our product candidates may not be considered medically necessary or cost-effective.
The U.S. government, state legislatures and foreign governments have shown significant interest in implementing cost containment programs to limit the growth of government-paid healthcare costs, including price controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs. In the United States, there has been heightened government scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several 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, reduce the cost of products under Medicare, and reform government program reimbursement methodologies for products. For example, at the federal level, on May 11, 2018, President Trump laid out his administration’s “Blueprint” to lower drug prices and reduce out of pocket costs of drugs that contains additional proposals to increase manufacturer competition, increase the negotiating power of certain federal healthcare programs, incentivize manufacturers to lower the list price of their products and reduce the out of pocket costs of drug products paid by consumers. On January 31, 2019, the Department of Health and Human Services (HHS) Office of Inspector General proposed modifications to federal Anti-Kickback Statute safe harbors which, among other things, if finalized, will affect discounts paid by manufacturers to Medicare Part D plans, Medicaid managed care organizations and pharmacy benefit managers working with these organizations. Although some of these and other proposals may require additional authorization to become effective, Congress and the Trump administration have each indicated that it will continue to seek new legislation and/or administrative measures to control pharmaceutical costs. In other countries, pricing and reimbursement schemes differ. In the European Community, governments influence the price of pharmaceutical products through their pricing and reimbursement rules and control of national healthcare systems that fund a large part of the cost of those products to consumers. The downward pressure on healthcare costs in general, and particularly prescription drugs, has become very intense. As a result, increasingly high barriers are being erected to the entry of new products. In addition, in some countries, cross‑border imports from low‑priced markets exert a commercial pressure on pricing within a country. There can be no assurance that any country that has price controls or reimbursement limitations for drug products will allow favorable reimbursement and pricing arrangements for any of our products.
Healthcare Reform
In the United States and foreign jurisdictions, there have been and will continue to be a number of legislative and regulatory proposals to change the healthcare system in ways that could affect our ability to sell our product candidates profitably, once they are approved for sale. Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives.
22
For example, in March 2010, President Obama signed into law the Patient Protection and Affordable Care Act, which, as amended by the Health Care and Education Reconciliation act of 2010 (Affordable Care Act) is a sweeping law 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. In the years since its enactment, there have been, and continue to be, significant developments in, and continued legislative activity around, attempts to repeal or repeal and replace the Affordable Care Act. On December 14, 2018, a Texas U.S. District Court Judge ruled that the Affordable Care Act is unconstitutional in its entirety because the “individual mandate” was repealed by Congress as part of the Tax Cuts and Jobs Act of 2017. While the Texas U.S. District Court Judge, as well as the Trump administration and Centers for Medicare & Medicaid Services, have stated that the ruling will have no immediate effect pending appeal of the decision, it is unclear how this decision, subsequent appeals, and other efforts to repeal and replace the Affordable Care Act will impact the Affordable Care Act. In addition, other reform measures have been proposed and adopted since the Affordable Care Act was enacted.
Additional new laws may result in additional reductions in funding to Medicare and other healthcare programs and other healthcare funding, which could have a material adverse effect on our customers and our financial operations. Further, new laws may, among other things, increase drug rebates or discounts owed under federal health care programs, impose additional reporting or compliance obligations, and/or otherwise put additional downward pressure on drug prices or increase the burden of compliance on pharmaceutical manufacturers.
Other Healthcare Laws and Compliance Requirements
In the United States, the research, manufacturing, distribution, sale and promotion of drug products and medical devices are potentially subject to regulation by various federal, state and local authorities in addition to the FDA, including the Centers for Medicare & Medicaid Services, other divisions of Health and Human Services (e.g., the Office of Inspector General), the U.S. Department of Justice, state Attorneys General, and other state and local government agencies. For example, sales, marketing and scientific/educational grant programs must comply with fraud and abuse laws such as the federal Anti‑Kickback Statute, as amended, the federal civil False Claims Act, as amended, and similar state laws. Pricing and rebate programs must comply with the Medicaid Drug Rebate Program requirements of the Omnibus Budget Reconciliation Act of 1990, as amended, and the Veterans Health Care Act of 1992, as amended. If products are made available to authorized users of the Federal Supply Schedule of the General Services Administration, additional laws and requirements apply. All of these activities are also potentially subject to federal and state consumer protection and unfair competition laws.
The federal Anti‑Kickback Statute prohibits, among other things, any person, including a prescription drug manufacturer (or a party acting on its behalf), from knowingly and willfully soliciting, receiving, offering or providing remuneration, directly or indirectly, to induce or reward either the referral of an individual, or the furnishing, recommending or arranging for a good or service, for which payment may be made under a federal healthcare program such as the Medicare and Medicaid programs. The federal civil False Claims Act imposes liability on any person or entity that, among other things, knowingly presents or causes to be presented, a false or fraudulent claim for payment by a federal healthcare program. The qui tam provisions of the federal civil False Claims Act allow a private individual to bring civil actions on behalf of the federal government alleging that the defendant has submitted a false claim to the federal government, and to share in any monetary recovery. In recent years, the number of suits brought by private individuals has increased dramatically. In addition, various states have enacted anti-kickback statues and false claims laws analogous to the federal civil False Claims Act. Also, the Health Insurance Portability and Accountability Act of 1996 (HIPAA) created several additional federal crimes, including healthcare fraud, and false statements relating to the delivery of or payments for healthcare benefits, items or services. HIPAA, as amended the Health Information Technology for Economic and Clinical Health Act (HITECH), and its implementing regulations also established uniform federal standards for certain “covered entities” (certain healthcare providers, health plans and healthcare clearinghouses) and their “business associates” (individuals and entities that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity) governing the conduct of certain electronic healthcare transactions and protecting the security and privacy of protected health information. In addition, we may be subject to physician payment transparency laws and patient privacy and security regulation by the federal government and by the states and foreign jurisdictions in which we conduct our business.
23
Because of the breadth of these laws and the narrowness of available statutory exceptions and regulatory safe harbors, it is possible that some of our business activities could be subject to challenge under one or more of such laws. If our operations are found to be in violation of any of the federal and state laws described above or any other governmental regulations that apply to us, we may be subject to penalties, including criminal and significant civil monetary penalties, damages, fines, imprisonment, exclusion from participation in government healthcare programs, 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 or refusal to allow us to enter into supply contracts, including government contracts, additional oversight and reporting obligations, 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.
Europe / Rest of World Government Regulation
In addition to regulations in the United States, we, and our collaborators, will be subject to a variety of regulations in other jurisdictions governing, among other things, clinical trials and any commercial sales, marketing and distribution of our products, similar or more stringent than the U.S. laws.
Whether or not we, or our collaborators, obtain FDA approval for a product, we must obtain the requisite approvals from regulatory authorities in foreign countries prior to the commencement of clinical trials or marketing of the product in those countries. The requirements and process governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country. In addition, we and our collaborators may be subject to foreign laws and regulations and other compliance requirements, including, without limitation, anti‑anti-kickback laws, false claims laws and other fraud and abuse laws, as well as laws and regulations requiring transparency of pricing and marketing information and governing the privacy and security of health information, such as the European Union’s Directive 95/95/46 on the Protection of Individuals with regard to the Processing of Personal Data.
25
If we, or our collaborators, 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.
Employees
As of December 31, 2018, we had 156 employees, all of whom were full‑time, 46 of whom hold Ph.D. or M.D. degrees, 128 of whom were engaged in research and development activities and 28 of whom were engaged in business development, finance, information systems, facilities, human resources or administrative support. None of our employees are represented by any collective bargaining unit. We believe that we maintain good relations with our employees.
Corporate Information
We were incorporated in California in August 1997 under the name Xencor. In September 2004, we reincorporated in the state of Delaware under the name Xencor, Inc. Our principal offices are located at 111 West Lemon Avenue, Monrovia, CA 91016, and our telephone number is (626) 305‑5900.305-5900. Our website address is www.xencor.com. Our website and the information contained on, or that can be accessed through, the website will not be deemed to be incorporated by reference in and are not considered part of this Annual Report on Form 10‑K (the Annual Report).Report. Our Annual Reports on Form 10‑K,10-K, Quarterly Reports on Form 10‑Q,10-Q, Current Reports on Form 8‑K8-K and amendments to reports filed or furnished pursuant to Section 13(a) and 15(d) of the Securities Exchange Act of 1934, as amended, are available free of charge on the Investor Relations portion of our web site at www.xencor.com as soon as reasonably practical after we electronically file such material with, or furnish it to, the Securities and Exchange Commission.Commission (SEC). The SEC maintains an internet site that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC and state the address of that site (www.sec.gov).
Item 1A. Risk Factors.
Summary of Risk Factors
We are subject to a number of risks that if realized could materially harm our business, prospects, operating results, and financial condition. Some of the more significant risks and uncertainties we face include those summarized below. The summary below is not exhaustive and is qualified by reference to the full set of risk factors set forth in this “Risk Factors” section. Please carefully consider all of the information in this Form 10-K, including the full set of risks set forth in this
“Risk Factors” section, and in our other filings with the U.S. Securities and Exchange Commission before making an investment decision regarding Xencor.
We have reviewed our risk factors and categorized them into five specific categories:
| 1. | Risks related to our unique and specific business operations as a small biotechnology company. These risks include: |
| ● | Our success depends on our ability to use and expand our XmAb technology platform to build a pipeline of product candidates and develop marketable products. We cannot be certain our candidates will receive regulatory approval or be successfully commercialized. |
| ● | The clinical development stage of our operations may make it difficult for you to evaluate the success of our business to date and to assess our future viability. |
| ● | The COVID-19 pandemic and the future outbreak of other highly infectious or contagious diseases could materially and adversely impact or disrupt our business and our financial condition, results of operations, cash flows and performance. |
| 2. | Risks specifically related to our financial position, capital requirements and ownership of our common stock. These risks include: |
| ● | We have incurred significant losses since our inception and anticipate that we will continue to incur significant losses for the foreseeable future. |
| ● | Biopharmaceutical product development is a highly speculative undertaking and involves a substantial degree of uncertainty. We have never generated any revenue from product sales and may never be profitable. |
| ● | We will require additional financing and may be unable to raise sufficient capital, which could lead us to delay, reduce or abandon research and development programs or commercialization. |
| ● | The market price of our common stock is likely to be highly volatile, and you could lose all or part of |
2426
| your investment. |
| ● | Our principal stockholders, directors and management own a significant percentage of our stock and will be able to exert significant control over matters subject to stockholder approval. |
| ● | Raising additional funds through debt or equity financing may be dilutive or restrict our operations and raising funds through licensing may require us to relinquish rights to our technology or product candidates. |
| ● | Future sales and issuances of our common stock or rights to purchase common stock, including pursuant to our equity incentive plans, could result in additional dilution of the percentage ownership of our stockholders and could cause our stock price to fall. |
| 3. | Risks related to our intellectual property. These risks include: |
| ● | If we are unable to obtain, maintain and enforce intellectual property protection covering our products, others may be able to make, use or sell products substantially the same as ours, which could adversely affect our ability to compete in the market. |
| ● | We have in-licensed, and may in the future in-license, a portion of our intellectual property, and, if we fail to comply with our obligations under these arrangements, we could lose such intellectual property rights or owe damages to the licensor of such intellectual property. |
| ● | We may be required to reduce the scope of our intellectual property due to third party intellectual property claims. |
| ● | Our products could infringe patents and other property rights of others, which may result in costly litigation and, if we are not successful, could cause us to pay substantial damages or limit our ability to commercialize our products, which could have a material adverse effect on our business. |
| ● | If we are not able to prevent disclosure of our trade secrets and other proprietary information, the value of our technology and products could be significantly diminished. |
| ● | If we do not obtain patent term extension and data exclusivity for any therapeutic candidates we develop, our business may be materially harmed. |
| 4. | Risks related to our dependence on third parties. These risks include: |
| ● | Our patent protection and prosecution for some of our product candidates is dependent on third parties. |
| ● | We rely on third party manufacturers for the manufacture of our XmAb engineered antibodies. This entails a complex process and manufacturers often encounter difficulties in production. If we, or any of our third-party manufacturers, encounter any loss of our master cell banks or if any of our third party manufacturers otherwise fail to comply with their contractual obligations, the development or commercialization of our product candidates could be delayed or stopped. |
| ● | Our existing partnerships are important to our business, and future partnerships may also be important to us. If we are unable to maintain any of these partnerships, or if these partnerships are not successful, our business could be adversely affected. |
| ● | We rely upon third party contractors, and service providers for the execution of most aspects of our development programs. Failure of these collaborators to provide services of a suitable quality and within acceptable timeframes may cause the delay or failure of our development programs. |
| ● | We rely on third parties to manufacture supplies of our preclinical and clinical product candidates. The development of such candidates could be stopped or delayed if any such third party fails to provide us with sufficient quantities of product or fails to do so at acceptable quality levels or prices or fails to maintain or achieve satisfactory regulatory compliance. |
| 5. | Risks related to our industry. These risks include: |
| ● | Clinical trials are expensive and take years to conduct, and the outcome of such clinical trials is uncertain. Clinical trials may fail to prove our product candidates are safe and effective. This could lead to delays, downsizing or termination of clinical development plans for any our product candidates. |
| ● | Adverse side effects or other safety risks associated with our product candidates could delay or preclude |
27
| approval, cause us to suspend or discontinue clinical trials, abandon product candidates, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any. |
| ● | If we experience delays or difficulties in the enrollment of patients in clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented. |
| ● | Our industry is subject to competition for skilled personnel and the challenges we face to identify and retain key personnel could impair our ability to effectively conduct and grow our operations. |
| ● | The development and commercialization of biologic products is subject to extensive regulation, and we may not obtain regulatory approvals for any of our product candidates. |
| ● | We face significant competition from other biotechnology and pharmaceutical companies and our operating results will suffer if we fail to compete effectively. |
| ● | Our current and future relationships with healthcare professionals, principal investigators, consultants, customers, and third-party payors in the United States and elsewhere may be subject, directly or indirectly, to applicable anti-kickback, fraud and abuse, false claims, physician payment transparency, health information privacy and security and other healthcare laws and regulations, which could expose us to penalties. |
| ● | Present and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and affect the prices we may obtain. |
| ● | Even if we are able to commercialize any product candidates, our product candidates may be subject to unfavorable pricing regulations, third-party coverage and reimbursement policies or healthcare reform initiatives. |
| ● | Our business involves the controlled use of hazardous materials, and as such we are subject to environmental and occupational safety laws. Continued compliance with these laws may incur substantial costs and failure to maintain compliance could result in liability for damages that may exceed our resources. |
Risks Related To Our Company
Item 1A. Risk Factors.Our success depends on our ability to use and expand our XmAb technology platform to build a pipeline of product candidates and develop marketable products. We cannot be certain our candidates will receive regulatory approval or be successfully commercialized.
Except for the historical information contained herein or incorporated by reference, this Annual ReportWe use our proprietary XmAb technology platform to develop engineered antibodies, with an initial focus on four properties: immune inhibition, cytotoxicity, extended half-life and the information incorporated by reference contains forward‑looking statements that involve risks and uncertainties. These statements include projections aboutmost recently, heterodimeric Fc domains enabling molecules with dual target binding. This platform has led to our accounting and finances, plans and objectives for the future, future operating and economic performance and other statements regarding future performance. These statements are not guaranteescurrent pipeline of future performance or events. Our actual results may differ materially from those discussed here. Factors that could cause or contribute to differences in our actual results include those discussed in the following section,candidates as well as those discussedthe other programs that utilize our technology and that are being developed by our partners and licensees. While we believe our preclinical and clinical data to date, together with our established partnerships, has validated our platform to a degree, most of the programs are in Part II, Item 7 entitled “Management’s Discussionearly stages of development. Although drug candidates incorporating our Fc technology, or Fc candidates, have been approved by the FDA, other product candidates have not yet been, and Analysismay never lead to, approved or marketable therapeutic antibody products. Even if we are successful in continuing to build our pipeline, the potential candidates that we identify may not be suitable for clinical development, including as a result of Financial Conditiontheir harmful side effects, limited efficacy or other characteristics that indicate that they are unlikely to receive marketing approval and Resultsachieve market acceptance. If we do not successfully develop and commercialize product candidates, we may not be able to obtain product or partnership revenues in future periods, which would adversely affect our business, prospects, financial condition and results of Operations”operations.
The clinical development stage of our operations may make it difficult for you to evaluate the success of our business to date and elsewhere throughout this Annual Reportto assess our future viability.
Our operations to date have been limited to raising capital, staffing our company, developing our proprietary XmAb technology platform, identifying potential product candidates, conducting preclinical studies and inclinical trials, developing partnerships and business planning. We have conducted, or are currently conducting, early phase clinical trials for several product candidates, but have not completed any late stage clinical trials for these or any other documents incorporatedproduct candidate. We have not yet demonstrated our ability to successfully complete any pivotal clinical trials, obtain regulatory
28
approvals, manufacture a commercial scale product, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful product commercialization. Consequently, any predictions you make about our future success or viability may not be as accurate as they could be if we were further advanced in development of our product candidates.
In addition, we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors. We believe to be successful will need to transition from a company with a research and development focus to a company capable of supporting commercial activities. We may not be successful in this transition.
We expect our financial condition and operating results to continue to fluctuate significantly from quarter to quarter and year to year due to a variety of factors, many of which are beyond our control. Accordingly, you should not rely upon the results of any quarterly or annual periods as indications of future operating performance.
The COVID-19 pandemic and the future outbreak of other highly infectious or contagious diseases, could materially and adversely impact or disrupt our business and our financial condition, results of operations, cash flows and performance.
On March 11, 2020, the World Health Organization (WHO) declared the rapid spread of COVID-19 a global pandemic, and on March 19, the Governor of the State of California, where we are headquartered and where our principal place of business is located, implemented a mandatory stay at home order for residents working in non-critical businesses.
While we have managed to maintain our operations during the COVID-19 pandemic, additional developments with this pandemic or another epidemic or pandemic, could cause significant disruptions to our business operations, business operations of our partners, on whom we rely for potential revenue, and product development collaborations; operations of our third-party manufacturers and CROs, on which we rely to conduct our clinical trials; and to our clinical trials, including as a result of significant restrictions or bans on travel into and within the countries in which our manufacturers produce our product candidates or where we conduct our clinical trials. Such disruptions could impede, delay, limit or prevent our employees and CROs from continuing research and development activities.
Although the COVID-19 pandemic has not materially affected our clinical development for the year ended December 31, 2020, certain of our clinical programs have seen slower enrollment and there have also been delays in initiating new studies as a result of the COVID-19 pandemic. These delays are not seen across all our trials and are specific to certain trials enrolling at certain sites. In the future, the COVID-19 pandemic could further adversely affect our and our partners’ ability to enroll and recruit patients in current and future clinical trials. Our success is dependent on our ability and the ability of our partners to advance our wholly-owned and partnered development programs into later stages of clinical development. Many pharmaceutical and biotechnology companies have indicated that their clinical trials will be delayed and enrollment of current and ongoing trials will suffer as a result of the COVID-19 pandemic. Completion of our ongoing clinical and preclinical studies or commencement of new clinical trials could be impeded, delayed, limited or prevented by reference intothe effects of the COVID-19 pandemic and related restrictions including negative effects on the production, delivery or release of our product candidates to our clinical trial sites, as participation by our clinical trial investigators, patients or other critical staff, which to could delay data collection, analysis and other related activities, any of which could cause delay or denial of regulatory approval of our product candidates. The delay and impact on enrollment cannot be determined at this Annual Report. You should consider carefullytime and will depend on the following risk factors, togetherlength and severity of the COVID-19 pandemic. Continued delays on our clinical and preclinical studies or trials will increase our costs and expenses and seriously harm our operations and financial condition, which will adversely affect our business.
The COVID-19 pandemic could also potentially affect the business of the FDA as well as other health regulatory authorities, which could result in delays in our communications with these authorities and ultimately in the ability for us and our partners to have drug products approved.
29
The COVID-19 pandemic and mitigation measures also have had and may continue to have an adverse impact on global economic conditions which could have an adverse effect on our business and financial condition, including impairment of our ability to raise capital when needed. The trading prices for biopharmaceutical companies’ stock, including our common shares have been highly volatile as a result of the COVID-19 pandemic. In addition, a recession, depression, or other sustained adverse market event resulting from the COVID-19 pandemic could materially and adversely affect our business and the value of our common shares.
The COVID-19 pandemic could potentially affect our partnerships and collaborations which provide us with revenue and non-dilutive payments in the form of upfront payments, milestone payments, royalties, and cost-sharing of co-development programs. If our partners’ and collaborators’ operations are severely affected by the COVID-19 pandemic, it will adversely affect our future potential revenue from such partners and collaborators.
We have required most of our employees, including all of our administrative employees, to work remotely, restricted on-site staff to only those employees that must perform essential activities that must be completed on-site and limited the other information includednumber of staff allowed in our laboratory and offices. These changes may negatively impact productivity, or incorporateddisrupt, delay, or otherwise adversely impact our business. In addition, this could increase our cyber security risk, create data accessibility concerns, and make us more susceptible to communication disruptions, any of which could adversely impact our business operations. When we reopen our facilities, we could encounter delays in this Annual Report. Eachconnection with implementing precautionary measures to mitigate the risk of these risk factors, either alone or taken together,exposing our facilities and employees to COVID-19.
The COVID-19 pandemic could adversely affect our business, operating resultssupply chain for our research, development, and financial condition, as well asclinical programs. We rely on third party vendors for research supplies, development activities including manufacturing of drug product for our clinical studies and testing of drug material. In the third quarter of 2020, several manufacturing vendors notified us of critical supply shortages which will delay the development timelines for our earlier stage development programs by three to six months. We currently do not expect these supply shortages to delay the timelines for our programs that are already in clinical studies. However, if this supply disruption extends for more than the expected three to six months, it will extend the timelines for advancing our earlier stage programs further and could also delay the current timelines for advancing our existing clinical programs. If any other vendors in our supply chain of products or services are also severely affected from the COVID-19 pandemic, it will adversely affect our ability to continue our research and development activities and also continue our clinical trial activities.
The COVID-19 pandemic continues to rapidly evolve. Its ultimate impact on our business operations is highly uncertain and subject to change that will depend on future developments, which cannot be accurately predicted, including the valueduration of an investmentthe COVID-19 pandemic, additional or modified government actions, new information that will emerge concerning the severity and impact of COVID-19 and the actions taken to address its impact in our common stock. There may be additional risks that wethe short and long term, among others. We do not presentlyyet know the full extent of potential delays or that we currently believe are immaterial which could also impairimpacts on our business, our clinical trials, our research programs, healthcare systems or the global economy. We will continue to monitor the situation closely.
Risks Specifically Related to our Financial Position, Capital Requirements and financial position.
Risks Relating to Our Business and to the Discovery, Development, Regulatory ApprovalOwnership of Our Product Candidates and other Legal Compliance MattersCommon Stock
We have incurred significant losses since our inception and anticipate that we will continue to incur significant losses for the foreseeable future.
We are a clinical‑stageclinical-stage biopharmaceutical company. To date, we have financed our operations primarily through equity and debt financings and our research and development licensing agreements and have incurred significant operating losses since our inception in 1997. For the year ended December 31, 2018, our net loss was $70.5 million and our net loss for the year ended December 31, 2017 was $38.5 million. The only year that2020, we did not sustainincurred a net loss was the year ended December 31, 2016 when we earned a net income of $45.1 million. As$69.3 million and as of December 31, 2018,2020, we had an accumulated deficit of $323.3$365.7 million. We expect to incur additional losses in future years as we execute our plan to continue our discovery, research and development activities, including the ongoing and planned clinical development of our antibody product candidates, and incur the additional costs of operating as a public company. We are unable to predict the extent of any future losses or when we will become profitable, if ever. Even if we do achieve profitability, we may not be able to sustain or increase profitability on an ongoing basis which would adversely affect our business, prospects, financial condition and results of operations.
30
Biopharmaceutical product development is a highly speculative undertaking and involves a substantial degree of uncertainty. We have never generated any revenue from product sales and may never be profitable.
We have devoted substantially all of our financial resources and efforts to developing our proprietary XmAb technology platform, identifying potential product candidates and conducting preclinical studies and clinical trials. We and our partners are still in the early stages of developing our product candidates, and we have not completed development of any of our wholly-owned products. Our revenue to date has been primarily revenue from the license of our proprietary XmAb technology platform and drug candidates for the development of product candidates by others or revenue from our partners. Our ability to generate revenue and achieve profitability depends in large part on our ability, alone or with partners, to achieve milestones and to successfully complete the development of, obtain the necessary regulatory approvals for, and commercialize and market, product candidates. We do not anticipate generating revenues from sales of our own products forin the foreseeable future. future that will provide sufficient proceeds to fund our operations on an ongoing basis.
Our ability to generate future revenues from product saleslicensing our proprietary XmAb technologies and drug candidates depends heavily on our and our partners’ success in:
|
|
|
|
25
Tablein advancing drug candidate that they have licensed from us or developed using one of Contentsour technologies. Our partners face the same development, regulatory and market risk for advancing their drug candidates and their ability to successfully advance these partnered programs will affect potential milestones and royalties we could earn under our collaboration agreements. Further, our partners may decide not to pursue, or decide to deprioritize our programs due to changing priorities which could affect our future potential revenue from such arrangements.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Because of the numerous risks and uncertainties associated with biologic product development, we are unable to predict the timing or amount of increased expenses and when we will be able to achieve or maintain profitability, if ever. In addition, our expenses could increase beyond expectations if we are required by the U.S. Food and Drug Administration (FDA),FDA, or foreign regulatory agencies, to perform studies and trials in addition to those that we currently anticipate, or if there are any delays in our or our partners completing clinical trials or the development of any of our product candidates. If one or more of the product candidates that we independently develop is approved for commercial sale, we anticipate incurring significant costs associated with commercializing such product candidates. Even if we or our partners are able to generate revenues from the sale of any approved products, we may not become profitable and may need to obtain additional funding to continue operations, which may not be available to us on favorable terms, if at all. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable would depress the value of our company and could impair our ability to raise capital, expand our business, maintain our research and development efforts, diversify our product offerings or even continue our operations. A decline in the value of our company could also cause you to lose all or part of your investment.
We will require additional financing and may be unable to raise sufficient capital, which could lead us to delay, reduce or abandon research and development programs or commercialization.
As of December 31, 2018,2020, we had $530.5$604.0 million in cash, cash equivalents and marketable securities. We expect our expenses to increase in connection with our ongoing development activities, including the continued development of our pipeline of bispecific drug candidates including XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104, and XmAb24306 and other research activities. Identifying potential product candidates and conducting preclinical testing and clinical trials are time‑consuming,time-consuming, expensive and uncertain processes that take years to complete, and we or our partners may never generate the necessary data or results required to obtain regulatory approval and achieve product sales. In addition, our product candidates, if approved, may not achieve commercial success.
26
Our commercial revenues, if any, will be derived from sales of products that we do not expect to be commercially available for many years, if at all. If we obtain regulatory approval for any of our product candidates, we expect to incur significant commercialization expenses related to product manufacturing, marketing, sales and distribution. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research and development programs or any future commercialization efforts.
We believe our existing cash, cash equivalents and marketable securities, together with interest thereon and expected milestones and royalty payments will be sufficient to fund our operations beyond the end ofinto 2024. However, changing circumstances or inaccurate estimates by us may cause us to use capital significantly faster than we currently anticipate, and we may need to spend more money than currently expected because of circumstances beyond our control. For example, our current and our planned clinical trials for XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104, and XmAb24306 or clinical trials for other drug candidates may encounter technical, enrollment or other issues that could cause our development costs to increase more than we expect. Under the Genentech Agreement, we will be sharing 45% of development costs worldwide for XmAb24306 and other IL-15 programs, and under the Novartis Agreement, we are co-developing XmAb14045 worldwide and sharing development costs. We do not have sufficient cash to complete the clinical development of any of our product candidates and will require additional funding to complete the development activities required for regulatory approval of XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104, or XmAb24306our current product candidates or any other future product candidates that we develop independently. 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
31
and commercialize our product candidates. Adequate additional financing may not be available to us on acceptable terms, or at all. In addition, we may seek additional capital due to favorable market conditions or strategic considerations; even if we believe we have sufficient funds for our current or future operating plans. If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research and development programs or any future commercialization efforts.
The developmentmarket price of our common stock is likely to be highly volatile, and commercializationyou could lose all or part of biologic productsyour investment.
Prior to our initial public offering (IPO), there was no public market for our common stock. The trading price of our common stock is likely to be volatile. Since our IPO, the trading price of our common stock has ranged from a low of approximately $5.75 to a high of approximately $55.33. Our stock price could be subject to extensive regulation,wide fluctuations in response to a variety of factors, including the following:
| 1. | adverse results or delays, or cancellations of clinical trials by us or our partners; |
| 2. | inability to obtain additional funding; |
| 3. | changes in laws or regulations applicable to our products; |
| 4. | inability to obtain adequate product supply for our product candidates, or the inability to do so at acceptable prices; |
| 5. | adverse regulatory decisions; |
| 6. | changes in the structure of healthcare payment systems; |
| 7. | introduction of new products or technologies by our competitors; |
| 8. | failure to meet or exceed product development or financial projections we provide to the public; |
| 9. | the perception of the pharmaceutical and biotechnology industry by the public, legislatures, regulators and the investment community; |
| 10. | announcements of significant acquisitions, strategic partnerships, joint ventures or capital commitments by us or our competitors; |
| 11. | disputes or other developments relating to proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies; |
| 12. | additions or departures of key scientific or management personnel; |
| 13. | significant lawsuits, including patent or stockholder litigation; |
| 14. | changes in the market valuations of similar companies; |
| 15. | sales of our common stock by us or our stockholders in the future; and |
| 16. | trading volume of our common stock. |
In addition, the stock market in general, and the Nasdaq Global Market and biotechnology companies in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies. Broad market and industry factors may negatively affect the market price of our common stock, regardless of our actual operating performance.
32
In the past, securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for us because biopharmaceutical companies have experienced significant stock price volatility in recent years. If we face such litigation, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business.
Our principal stockholders, directors and management own a significant percentage of our stock and will be able to exert significant control over matters subject to stockholder approval.
Based on information available to us as of December 31, 2020 our executive officers, directors, 5% stockholders and their affiliates beneficially owned, as a group, approximately 67% of our voting stock.
Therefore, our officers, directors and 5% stockholders and their affiliates will have the ability to influence us through this ownership position and so long as they continue to beneficially own a significant amount of our outstanding voting stock. These stockholders may be able to determine all matters requiring stockholder approval and this concentration of ownership may deprive other stockholders from realizing the true value of our common stock. For example, these stockholders, acting together, may be able to control elections of directors, amendments of our organizational documents, or approval of any merger, sale of assets, or other major corporate transaction. This may prevent or discourage unsolicited acquisition proposals, offers for our common stock or other transactions or arrangements that you may believe are in your best interest as one of our stockholders.
Raising additional funds through debt or equity financing may be dilutive or restrict our operations and raising funds through licensing may require us to relinquish rights to our technology or product candidates.
To the extent that additional capital is raised through the sale of equity or convertible debt securities, the issuance of those securities could result in substantial dilution for our current stockholders and the terms may include liquidation or other preferences that adversely affect the rights of our current stockholders. Existing stockholders may not agree with our financing plans or the terms of such financings. If we are unable to obtain additional funding on required timelines, we may be required to:
1. seek collaborators for one or more of our product candidates at an earlier stage than otherwise would be desirable or on terms that are less favorable than might otherwise be available;
2. relinquish or license on unfavorable terms our rights to technologies or product candidates that we otherwise would seek to develop or commercialize ourselves; or
3. significantly curtail one or more of our research or development programs or cease operations altogether. Additional funding may not be available to us on acceptable terms, or at all.
Future sales and issuances of our common stock or rights to purchase common stock, including pursuant to our equity incentive plans, could result in additional dilution of the percentage ownership of our stockholders and could cause our stock price to fall.
We expect that significant additional capital will be needed in the future to continue our planned operations. To the extent we raise additional capital by issuing equity securities, our stockholders may experience substantial dilution. We may sell common stock, convertible securities, or other equity securities in one or more transactions at prices and in a manner, we determine from time to time. These sales may also result in material dilution to our existing stockholders, and new investors could gain rights superior to our existing stockholders.
Pursuant to our 2013 equity incentive plan (2013 plan), subject to board approval, our management is authorized to grant stock options and other equity-based awards to our employees, directors and consultants. The number of shares available for future grant under the 2013 plan will automatically increase each year until 2023 by 4% of all shares of our capital stock outstanding as of December 31 of the prior calendar year, subject to the ability of our Board of Directors to take action to reduce the size of the increase in any given year. As of December 31, 2020, we had options to purchase 7,751,789 shares outstanding under our equity compensation plans. In addition, we are also authorized to
33
grant equity awards, including stock options, to our employees, directors and consultants, covering up to 11,479,096 shares of our common stock, pursuant to our equity compensation plans. We plan to register the number of shares available for issuance or subject to outstanding awards under our equity compensation plans. If our Board of Directors elects to increase the number of shares available for future grant by the maximum amount each year, our stockholders may experience additional dilution, which could cause our stock price to fall.
If our internal control over financial reporting is not effective, we may not be able to accurately report our financial results or file our periodic reports in a timely manner, which may cause investors to lose confidence in our reported financial information and may lead to a decline in our stock price.
Effective internal control over financial reporting is necessary for us to provide reliable financial reports in a timely manner. If we fail to adequately staff our accounting and finance function to address the additional demands that will be placed upon us as a public company, including the requirements of the Sarbanes-Oxley Act of 2002, or fail to maintain adequate internal control over financial reporting, it could prevent our management from concluding our internal control over financial reporting is effective and impair our ability to prevent material misstatements in our financial statements, which could cause our business to suffer.
As a large accelerated filer, we are subject to additional internal control requirements of the Sarbanes-Oxley Act of 2002.
Sales of a substantial number of shares of our common stock by our existing stockholders in the public market could cause our stock price to fall.
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. In addition, a substantial number of shares of common stock are subject to outstanding options that are or will become 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.
Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited.
Our net operating loss (NOL) carryforwards generated in tax years ending on or prior to December 31, 2017, are only permitted to be carried forward for 20 years under applicable U.S. tax law. Under the TCJA, our federal NOLs generated in tax years ending after December 31, 2017, may be carried forward indefinitely, but the deductibility of such federal NOLs generated in tax years beginning after December 31, 2020, is limited. It is uncertain if and to what extent various states will conform to the TCJA. In addition, under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, and corresponding provisions of state law, if a corporation undergoes an “ownership change,” which is generally defined as a greater than 50% change, by value, in its equity ownership over a three-year period, the corporation’s ability to use its pre-change NOL carryforwards and other pre-change U.S. tax attributes (such as research tax credits) to offset its post-change income or taxes may be limited. It is also possible that we have in the past undergone, and in the future may undergo, ownership changes that could result in additional limitations on our net operating loss and tax credit carryforwards.
As a result, our pre-2018 NOL carryforwards may expire prior to being used. Similar provisions of state tax law may also apply to limit our use of accumulated state tax attributes. In addition, at the state level, there may be periods during which the use of NOLs is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed. As a result, if we earn net taxable income, we may be unable to use all or a material portion of our NOLs and other tax attributes, which could potentially result in increased future tax liability to us and adversely affect our future cash flows.
We do not intend to pay dividends on our common stock so any returns will be limited to the value of our stock.
We have never declared or paid any cash dividend on our common stock. We currently anticipate that we will retain future earnings for the development, operation and expansion of our business and do not anticipate declaring or
34
paying any cash dividends for the foreseeable future. Any return to stockholders will therefore be limited to the appreciation of their stock.
Provisions in our amended and restated certificate of incorporation and bylaws, as well as provisions of Delaware law, could make it more difficult for a third party to acquire us or increase the cost of acquiring us, even if doing so would benefit our stockholders or remove our current management.
Some provisions of our charter documents and Delaware law may have anti-takeover effects that could discourage an acquisition of us by others, even if an acquisition would be beneficial to our stockholders and may prevent attempts by our stockholders to replace or remove our current management. These provisions include:
| ● | authorizing the issuance of “blank check” preferred stock, the terms of which may be established and shares of which may be issued without stockholder approval; |
| ● | prohibiting stockholder action by written consent, thereby requiring all stockholder actions to be taken at a meeting of our stockholders; |
| ● | eliminating the ability of stockholders to call a special meeting of stockholders; and |
| ● | establishing advance notice requirements for nominations for election to the Board of Directors or for proposing matters that can be acted upon at stockholder meetings. |
These provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our Board of Directors, which is responsible for appointing the members of our management. In addition, we are subject to Section 203 of the Delaware General Corporation Law, which generally prohibits a Delaware corporation from engaging in any of a broad range of business combinations with an interested stockholder for a period of three years following the date on which the stockholder became an interested stockholder, unless such transactions are approved by our Board of Directors. This provision could have the effect of delaying or preventing a change of control, whether or not it is desired by or beneficial to our stockholders. Further, other provisions of Delaware law may also discourage, delay, or prevent someone from acquiring us or merging with us. Any provision of our certificate of incorporation or bylaws or Delaware law that has the effect of delaying or deterring change in control could limit the opportunity for our stockholders to receive a premium for their shares of our common stock, and could also affect the price that some investors are willing to pay for our common stock.
Requirements associated with being a public reporting company will continue to increase our costs significantly, as well as divert significant company resources and management attention.
We have been subject to the reporting requirements of the Exchange Act and the other rules and regulations of the Securities and Exchange Commission (SEC) since December 2013. Effective for the year-ended December 31, 2016, we became a large accelerated filer and are subject to additional internal control and SEC reporting obligations. Compliance with the various reporting and other requirements applicable to public reporting companies requires considerable time, attention of management, and financial resources.
Further, the listing requirements of The Nasdaq Global Market require that we satisfy certain corporate governance requirements relating to director independence, distributing annual and interim reports, stockholder meetings, approvals, and voting, soliciting proxies, conflicts of interest and a code of conduct. Our management and other personnel need to devote a substantial amount of time to ensure that we comply with all of these requirements. Moreover, the reporting requirements, rules and regulations increase our legal and financial compliance costs and also make some activities more time-consuming and costly. These reporting requirements, rules, and regulations, coupled with the increase in potential litigation exposure associated with being a public company, could also make it more difficult for us to attract and retain qualified persons to serve on our Board of Directors or board committees or to serve as executive officers, or to obtain certain types of insurance, including directors’ and officers’ insurance, on acceptable terms.
35
In addition, being a public company could make it more difficult or more costly for us to obtain certain types of insurance, including directors’ and officers’ liability insurance, and we may be forced to accept reduced policy limits and coverage or incur substantially higher costs to obtain the same or similar coverage. The impact of these events could also make it more difficult for us to attract and retain qualified persons to serve on our Board of Directors, our Board committees, or as executive officers.
Any changes we make to comply with these obligations may not be sufficient to allow us to satisfy our obligations as a public company on a timely basis, or at all.
Risks Related to Our Intellectual Property
If we are unable to obtain, regulatory approvals for any ofmaintain and enforce intellectual property protection covering our product candidates.
The clinical development, manufacturing, labeling, packaging, storage, recordkeeping, advertising, promotion, export, import, marketing and distribution and other possible activities relatingproducts, others may be able to XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104, and XmAb24306make, use or sell products substantially the same as ours, which could adversely affect our current lead antibody product candidates, as well as any other antibody product candidate that we may developability to compete in the future, are subject to extensive regulationmarket.
Our commercial success depends, in the United States as biologics. Biologics require the submission of a Biologics License Application (BLA) to the FDA and we are not permitted to market any product candidate in the United States until we obtain approval from the FDA of a BLA for that product. A BLA must be supported by extensive clinical and preclinical data, as well as extensive information regarding chemistry, manufacturing and controls (CMC) sufficient to demonstrate the safety, purity, potency and effectiveness of the applicable product candidate to the satisfaction of the FDA.
Regulatory approval of a BLA is not guaranteed, and the approval process is an expensive and uncertain process that may take several years. The FDA and foreign regulatory entities also have substantial discretion in the approval process. The number and types of preclinical studies and clinical trials that will be required for BLA approval varies dependingpart, on the product candidate, the disease or the condition that the product candidate is designed to target and the regulations applicable to any particular product candidate. Despite the time and expense associated with preclinical studies and clinical trials, failure can occur at any stage, and we could encounter problems that require us to repeat or perform additional preclinical studies or clinical trials or generate additional CMC data. The FDA and similar foreign authorities could delay, limit or deny approval of a product candidate for many reasons, including because they:
|
|
|
|
|
|
27
|
|
|
|
|
|
Generally, public concern regarding the safety of drug and biologic products could delay or limit our ability to obtain, regulatory approval, result inmaintain and enforce patents, trade secrets, trademarks and other intellectual property rights and to operate without having third parties infringe, misappropriate or circumvent the inclusionrights that we own or license. The value of unfavorable information inmany of our labeling, or require us to undertake other activities that may entail additional costs.
We have not submitted an application for approval or obtained FDA approval for any product. This lack of experience may impede our abilitypartnered licensing arrangements is based on the underlying intellectual property and related patents. If we are unable to obtain, FDA approval in a timely manner, if at all, formaintain and enforce intellectual property protection covering our product candidates.
To market any biologics outside of the United States, we and currentproducts or future collaborators must comply with numerous and varying regulatory and compliance related requirements of other countries. Approval procedures vary among countries and can involve additional product testing and additional administrative review periods, including obtaining reimbursement and pricing approval in select markets. The time required to obtain approval in other countries might differ from that required to obtain FDA approval. The regulatory approval process in other countries may include all of the risks associated with FDA approval as well as additional, presently unanticipated, risks. 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 inunderlying technologies, others including the risk that our product candidates may not be approved for all indications requested and that such approval may be subjectable to limitations onmake, use or sell products that are substantially the indicated uses for whichsame as ours without incurring the drug may be marketed. Certain countriessizeable development and licensing costs that we have a very difficult reimbursement environment and we may not obtain reimbursement or pricing approval, if required, in all countries where we expect to market a product, or we may obtain reimbursement approval at a level that would make marketing a product in certain countries not viable.
If we experience delays in obtaining approval or if we fail to obtain approval of our product candidates, the commercial prospects for our product candidates may be harmed and our ability to generate revenues will be materially impairedincurred, which would adversely affect our business, prospects, financial conditionability to compete in the market. As of December 31, 2020, we held over 1,000 issued patents and resultspending patent applications. We file patent applications in the United States, Canada, Japan, Europe and other major markets either directly or via the Patent Cooperation Treaty. Our ability to stop third parties from making, using, selling, offering to sell or importing our product candidates is dependent upon the extent to which we have rights under valid and enforceable patents or trade secrets that cover these activities. However, the patent positions of operations.
Even ifbiopharmaceutical companies, including ours, can be highly uncertain and involve complex legal and factual questions for which important legal principles remain unresolved. No consistent policy regarding the breadth of claims allowed in patents in these fields has emerged to date in the United States. The U.S. patent laws have recently changed, there have been changes regarding how patent laws are interpreted, and the U.S. Patent and Trademark Office (the PTO) has also implemented changes to the patent system. Some of these changes are currently being litigated, and we cannot accurately determine the outcome of any such proceedings or predict future changes in the interpretation of patent laws or changes to patent laws which might be enacted into law. Those changes may materially affect our patents, our ability to obtain patents or the patents and applications of our collaborators and licensors. The patent situation in the biopharmaceutical industry outside the United States is even more uncertain. Therefore, there is no assurance that our pending patent applications will result in the issuance of patents or that we will develop additional proprietary products which are patentable. Moreover, patents issued or to be issued to us may not provide us with any competitive advantage. Our patent position is subject to numerous additional risks, including the following:
| 1. | we may fail to seek patent protection for inventions that are important to our success; |
| 2. | our pending patent applications may not result in issued patents; |
| 3. | we cannot be certain that we are the first to invent the inventions covered by pending patent applications or that we were the first to file such applications and, if we are not, we may be subject to priority disputes; |
| 4. | we may be required to disclaim part or all of the term of certain patents or all of the term of certain patent applications; |
| 5. | we may file patent applications but have claims restricted or we may not be able to supply sufficient data to support our claims and, as a result, may not obtain the original claims desired or we may receive restricted claims. Alternatively, it is possible that we may not receive any patent protection from an application; |
36
| 6. | we could inadvertently abandon a patent or patent application, resulting in the loss of protection of certain intellectual property rights in a certain country. We, our collaborators or, our patent counsel may take action resulting in a patent or patent application becoming abandoned which may not be able to be reinstated or if reinstated, may suffer patent term adjustments; |
| 7. | the claims of our issued patents or patent applications when issued may not cover our product candidates; |
| 8. | no assurance can be given that our patents would be declared by a court to be valid or enforceable or that a competitor’s technology or product would be found by a court to infringe our patents. Our patents or patent applications may be challenged by third parties in patent litigation or in proceedings before the PTO or its foreign counterparts, and may ultimately be declared invalid or unenforceable, or narrowed in scope; |
| 9. | there may be prior art of which we are not aware that may affect the validity or enforceability of a patent claim. There also may be prior art of which we are aware, but which we do not believe affects the validity or enforceability of a claim, which may, nonetheless, ultimately be found to affect the validity or enforceability of a claim; |
| 10. | third parties may develop products which have the same or similar effect as our products without infringing our patents. Such third parties may also intentionally circumvent our patents by means of alternate designs or processes or file applications or be granted patents that would block or hurt our efforts; |
| 11. | there may be dominating patents relevant to our product candidates of which we are not aware; |
| 12. | our patent counsel, lawyers or advisors may have given us, or may in the future give us incorrect advice or counsel. Opinions from such patent counsel or lawyers may not be correct or may be based on incomplete facts; |
| 13. | obtaining regulatory approval for biopharmaceutical products is a lengthy and complex process, and as a result, any patents covering our product candidates may expire before, or shortly after such product candidates are approved and commercialized; |
| 14. | the patent and patent enforcement laws of some foreign jurisdictions do not protect intellectual property rights to the same extent as laws in the United States, and many companies have encountered significant difficulties in protecting and defending such rights in foreign jurisdictions. If we encounter such difficulties or we are otherwise precluded from effectively protecting our intellectual property rights in foreign jurisdictions, our business prospects could be substantially harmed; and |
| 15. | we may not develop additional proprietary technologies that are patentable. |
Any of these factors could hurt our ability to gain full patent protection for our products. Registered trademarks and trademark applications in the United States and other countries are subject to similar risks as described above for patents and patent applications, in addition to the risks described below.
Many of our product development partnership agreements are complex and may call for licensing or cross-licensing of potentially blocking patents, know-how or intellectual property. Due to the potential overlap of data, know-how and intellectual property rights there can be no assurance that one of our collaborators will not dispute our right to use, license or distribute data, know-how or other intellectual property rights, and this may potentially lead to disputes, liability or termination of a program. There are no assurances that our actions or the actions of our collaborators would not lead to disputes or cause us to default with other collaborators. For example, we may become involved in disputes with our collaborators relating to the ownership of intellectual property developed in the course of the partnership. We also cannot be certain that a collaborator will not challenge the validity or enforceability of the patents we license.
37
We cannot be certain that any country’s patent and/or trademark office will not implement new rules which could seriously affect how we draft, file, prosecute and/or maintain patents, trademarks and patent and trademark applications. We cannot be certain that increasing costs for drafting, filing, prosecuting and maintaining patents, trademarks and patent and trademark applications will not restrict our ability to file for patent protection. For example, we may elect not to seek patent protection in certain jurisdictions or for certain inventions in order to save costs. We may be forced to abandon or return the rights to specific patents due to a lack of financial resources.
We intend to file applications for trademark registrations in connection with our product candidates in various jurisdictions, including the United States. No assurance can be given that any of our trademark applications will be registered in the United States or elsewhere, or that the use of any registered or unregistered trademarks will confer a competitive advantage in the marketplace. Furthermore, even if we are successful in our trademark registrations, the FDA and regulatory authorities in other countries have their own process for drug nomenclature and their own views concerning appropriate proprietary names. No assurance can be given that the FDA or any other regulatory authority will approve of any of our trademarks or will not request reconsideration of one of our trademarks at some time in the future. The loss, abandonment, or cancellation of any of our trademarks or trademark applications could negatively affect the success of the product candidates we will be subject to ongoing regulatory obligationswhich they relate.
We have in-licensed, and continued regulatory review, which may result in significant additional expense. Additionally,the future in-license, a portion of our product candidates, if approved, could be subject to labelingintellectual property, and, other restrictions and market withdrawal and we may be subject to penalties if we fail to comply with regulatory requirementsour obligations under these arrangements, we could lose such intellectual property rights or experience unanticipated problems withowe damages to the licensor of such intellectual property.
We currently rely, and may in the future rely, on certain intellectual property rights licensed from third parties to protect our products.
Any regulatory approvals thattechnology and certain product candidates, and we ormay enter into additional license agreements in the future. As part of our partners receivediscovery and development activities, we routinely evaluate in-licenses from academic and research institutions. We have licensed and sublicensed certain intellectual property relating to our Xtend technology from a third party. We have also sublicensed certain intellectual property rights related to our CD3 bispecific technology from a third party, and we have licensed certain intellectual property rights from a third party related to our tidutamab and our IL-15 product candidates. We also license certain rights to the underlying cell lines for all our product candidates from third parties. Under these licenses, we have no right to control patent prosecution of the intellectual property or to enforce the patents, and as such the licensed rights may not be adequately maintained by the licensors. The termination of these or other licenses could also prevent us from commercializing product candidates covered by the licensed intellectual property.
Furthermore, the research resulting in the in-licensed patents was developed in the course of research funded by the U.S. government. As a result, the U.S. government may have certain rights (“march-in rights”) to intellectual property embodied in our Xtend products. Government rights in certain inventions developed under a government-funded program include a non-exclusive, non-transferable, irrevocable worldwide license to use inventions for any governmental purpose. Circumstances that trigger march-in rights include, for example, failure to take, within a reasonable time, effective steps to achieve practical application of the invention in a field of use, failure to satisfy the health and safety needs of the public and failure to meet requirements of public use specified by federal regulations. Federal law requires any licensor of an invention that was partially funded by the federal government to obtain a covenant from any exclusive licensee to manufacture products using the invention substantially in the United States. The U.S. government also has the right to use and disclose, without limitation, scientific data relating to licensed technology that was developed in whole or in part at government expense. The government funding agency can elect to exercise these march-in rights on their own initiative or at the request of a third party. It is also possible that we might knowingly or unknowingly in-license additional technology that is subject to U.S. government march-in rights.
Our existing license agreements impose, and we expect that future license agreements will impose, various diligence, milestone payment, royalty and other obligations on us. If there is any conflict, dispute, disagreement or issue of non-performance between us and our licensing partners regarding our rights or obligations under the license agreements, including any such conflict, dispute or disagreement arising from our failure to satisfy payment obligations under any such agreement, we may owe damages, our licensor may have a right to terminate the affected license, and our and our partners' ability to utilize the affected intellectual property in our drug discovery and development efforts, and
38
our ability to enter into collaboration or marketing agreements for an affected product or therapeutic candidate, may be adversely affected.
We may be required to reduce the scope of our intellectual property due to third-party intellectual property claims.
Our competitors may have filed, and may in the future file, patent applications covering technology similar to 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 U.S. patent application on inventions similar to ours that claims priority to an application filed prior to March 16, 2013, we may have to participate in an interference proceeding declared by the PTO to determine priority of invention in the United States. The costs of these proceedings could be substantial, and it is possible that such efforts would be unsuccessful if, unbeknownst to us, the other party had independently arrived at the same or similar invention prior to our own invention, resulting in a loss of our U.S. patent position with respect to such inventions. In addition, changes enacted on March 15, 2013 to the U.S. patent laws under the America Invents Act resulted in the United States changing from a “first to invent” country to a “first to file” country. As a result, we may lose the ability to obtain a patent if a third-party files with the PTO first and could become involved in proceedings before the PTO to resolve disputes related to inventorship. We may also become involved in similar proceedings in other jurisdictions.
Furthermore, recent changes in U.S. patent law under the America Invents Act allows for post-issuance challenges to U.S. patents, including ex parte reexaminations, inter parte reviews and post-grant oppositions. There is significant uncertainty as to how the new laws will be subject to limitations on the approved indicated uses for which the productapplied and if our U.S. patents are challenged using such procedures, we may be marketednot prevail, possibly resulting in altered or to the conditionsdiminished claim scope or loss of approval, or contain requirements for potentially costly post‑marketing testing, including Phase 4 clinical trials, and surveillance to monitor the safety and efficacypatent rights altogether. Similarly, some countries, notably members of the product candidate. In addition,European Union, also have post grant opposition proceedings that can result in changes in scope and/or cancellation of patent claims.
Our products could infringe patents and other property rights of others, which may result in costly litigation and, if we are not successful, could cause us to pay substantial damages or limit our ability to commercialize our products, which could have a material adverse effect on our business.
Our commercial success depends upon our ability, and the FDA or a comparable foreign regulatory authority approves anyability of our collaborators, to develop, manufacture, market and sell our product candidates and use our proprietary technologies without infringing the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion, import, exportpatents and recordkeepingother proprietary rights of third parties. There is considerable intellectual property litigation in the biotechnology and pharmaceutical industries. For example, we are aware of issued patents owned by Merus B.V. (Merus) that may relate to and claim components of our bispecific antibody product candidates and partnered bispecific product candidates, including vibecotamab, plamotamab, tidutamab, XmAb717, XmAb104, XmAb841, and XmAb819 will putatively expire in 2033. We are additionally aware of several patents and pending applications directed to the use of IL-15 fused with Fc domains, and in some cases in combination with targeting domains, that might be relevant to XmAb306, with putative expirations ranging from 2025 to later than 2032. It is possible that these terms could be extended, for example, as a result of patent term restoration to compensate for regulatory delays. While we believe that our current development of these candidates currently falls into the “safe harbor” of non-infringement under 35 U.S.C. §271€(1), this protection terminates upon commercialization. In addition, there can be no assurance that our interpretation of this statutory exemption would be upheld. We believe there exists reasonable arguments of invalidity for the Genentech patent, the Merus patents and the IL-15 patents; however, we cannot assure that if challenged in litigation for infringement of these patents that we would prevail. In order to successfully challenge the validity of any issued U.S. patent, we would need to overcome a presumption of validity. This burden is a high one requiring us to present clear and convincing evidence as to the invalidity of such claims. There is no assurance that a court would find these claims to be invalid or not infringed.
In addition, as the biopharmaceutical industry expands and more patents are issued, the risk increases that there may be patents issued to third parties that relate to our products and technology of which we are not aware or that we must challenge to continue our operations as currently contemplated. Our products may infringe or may be alleged to infringe these patents. Because some patent applications in the United States may be maintained in secrecy until the patents are issued, because patent applications in the United States and many foreign jurisdictions are typically not published until eighteen months after filing and because publications in the scientific literature often lag behind actual discoveries, we cannot be certain that others have not filed patents that may cover our technologies, our product will be
39
candidates or their use. Additionally, pending patent applications which have been published can, subject to extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post‑marketing information and reports, registration, as well as continued compliance with current good manufacturing practices (cGMPs), and current good clinical practices (cGCPs), for any clinical trialscertain limitations, be later amended in a manner that we conduct post‑approval. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severitycould cover our technologies, our products or frequency, undesirable side effects caused by the product, problems encountered by our third‑party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, either before or after product approval, may result in, among other things:
|
|
|
|
28
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Additionally, if anyuse of our product candidates receivesproducts. We may become party to, or threatened with, future adversarial proceedings or litigation regarding intellectual property rights with respect to our products and technology. Third parties may assert infringement claims against us based on existing patents or patents that may be granted in the future.
If we are sued for patent infringement, we would need to demonstrate that our products or methods either do not infringe the patent claims of the relevant patent or that the patent claims are invalid, and we may not be able to do this. Proving invalidity 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. Even if we are successful in these proceedings, 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.
Any such claims are likely to be expensive to defend, and some of our competitors may be able to sustain the costs of complex patent litigation more effectively than we can because they have substantially greater resources.
If we are found to infringe a third party’s intellectual property rights, we could be required to obtain a license from such third party to continue developing and marketing approval,our products and technology. We may also elect to enter into such a license in order to settle litigation or in order to resolve disputes prior to litigation. 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 a license, it could be non-exclusive, thereby giving our competitors access to the FDAsame technologies licensed to us and could require us to adopt a REMSmake substantial royalty payments. We could also be forced, including by court order, to ensure thatcease commercializing the benefits of the therapy outweigh its risks, which may include, among other things, a medication guide outlining the risksinfringing technology or product. In addition, we could be found liable for distribution to patientsmonetary damages, including treble damages and a communication plan to health care practitioners.
Moreover, the FDA strictly regulates marketing, labeling, advertising and promotion of products. Drugs may be promoted only for the approved indications and in accordance with the provisions of the approved label, although physicians, in the practice of medicine, may prescribe approved drugs for unapproved indications. However, companies may share truthful and not misleading information that is otherwise consistent with the labeling. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that isattorneys’ fees if we are found to have improperly promoted off-label uses may be subject to significant liability.
Anywillfully infringed a patent. A finding of these eventsinfringement could prevent us from achievingcommercializing our product candidates or maintaining market acceptanceforce us to cease some of the product or the particular product candidate at issue andour business operations, which could significantlymaterially harm our business, prospects, financial condition and resultsbusiness. Claims that we have misappropriated the confidential information or trade secrets of operations.third parties could have a similar negative impact on our business.
The FDA’s policies 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 obtainedprevent disclosure of our trade secrets and we may not achieve or sustain profitability, which would adversely affectother proprietary information, the value of our business, prospects, financial conditiontechnology and results of operations.
If we experience delays or difficulties in the enrollment of patients in clinical trials, our receipt of necessary regulatory approvalsproducts could be delayedsignificantly diminished.
We rely on trade secret protection to protect our interests in proprietary know-how and in processes for which patents are difficult to obtain or prevented.
enforce. We may not be able to initiateprotect our trade secrets adequately. We have a policy of requiring our consultants, advisors, and collaborators to enter into confidentiality agreements and our employees to enter into invention, non-disclosure and non-compete agreements. However, no assurance can be given that we have entered into appropriate agreements with all parties that have had access to our trade secrets, know-how or continue clinical trialsother proprietary information. There is also no assurance that such agreements will provide for a meaningful protection of our producttrade secrets, know-how or other proprietary information in the event of any unauthorized use or disclosure of information. Furthermore, we cannot provide assurance that any of our employees, consultants, contract personnel, or collaborators, either accidentally or through willful misconduct, will not cause serious damage to our programs and/or our strategy, for example by disclosing important trade secrets, know-how or proprietary information to our competitors. It is also possible that our trade secrets, know-how or other proprietary information could be obtained by third parties as a result of breaches of our physical or electronic security systems. Any disclosure of confidential data into the public domain or to third parties could allow our competitors to learn our trade secrets and use the information in competition against us. In addition, others may independently discover our trade secrets and proprietary information. Any action to enforce our rights is likely to be time consuming and expensive, and may ultimately be unsuccessful, or may result in a remedy that is not commercially valuable. These risks are accentuated in foreign countries where laws or law enforcement practices may not protect proprietary rights as fully as in the United States or Europe. Any unauthorized disclosure of our trade secrets or proprietary information could harm our competitive position.
If we do not obtain patent term extension and data exclusivity for any therapeutic candidates ifwe develop, our business may be materially harmed.
Depending upon the timing, duration, and specifics of any FDA marketing approval of any therapeutic candidates we
40
may develop, one or more of our owned or licensed U.S. patents may be eligible for limited patent term extension under the Hatch-Waxman Act. Similar extensions as compensation for patent term lost during regulatory review processes are also available in certain foreign countries and territories, such as in Europe under a Supplementary Patent Certificate. However, we may not be granted an extension in the United States and/or foreign countries and territories because of, for example, failing to exercise due diligence during the testing phase or regulatory review process, 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 less than we request. If we are unable to locateobtain patent term extension or the term of any such extension is shorter than what we request or we fail to choose the most optimal patents to extend, our competitors may obtain approval of competing products following our patent expiration, and enroll a sufficient numberour business, financial condition, results of eligible patientsoperations and prospects could be materially harmed.
Risks Related to participate in these trials as required by the FDA or similar regulatory authorities outside the United States. In addition,Our Dependence on Third Parties
Our patent protection and prosecution for some of our competitors have ongoing clinical trials for product candidates that treatis dependent on third parties.
While we normally seek and gain the same indications asright to fully prosecute the patents relating to our product candidates, and patients who would otherwisethere may be eligible for our clinical trials may instead enroll in clinical trials of our competitors’ product candidates.
Patient enrollment is affected by other factors including:
|
|
29
|
|
|
|
|
|
|
|
|
|
|
|
Our inability to enroll a sufficient number of patients for any of our clinical trials could result in significant delays and could require us to abandon one or more clinical trials altogether. Enrollment delays in our clinical trials may result in increased development costs for our product candidates and in delays to commercially launchingare controlled by our product candidates, if approved, which would causelicensors.
We rely on third-party manufacturers for the valuemanufacture of our company to decline and limit our ability to obtain additional financing.
The manufacture of biopharmaceutical products, including XmAb‑engineered antibodies, isXmAb-engineered antibodies. This entails a complex process and manufacturers often encounter difficulties in production. If we, or any of our third‑partythird-party manufacturers, encounter any loss of our master cell banks or if any of our third‑partythird-party manufacturers encounter other difficulties, or otherwise fail to comply with their contractual obligations, our ability to provide product candidates for clinical trials or our products to patients, once approved, the development or commercialization of our product candidates could be delayed or stopped.
The manufacture of biopharmaceutical products is complex and requires significant expertise and capital investment, including the development of advanced manufacturing techniques and process controls. We and our contract manufacturers must comply with cGMP regulations and guidelines. Manufacturers of biopharmaceutical products often encounter difficulties in production, particularly in scaling up and validating initial production and contamination. These problems include difficulties with production costs and yields, quality control, including stability of the product, quality assurance testing, operator error, shortages of qualified personnel, as well as compliance with strictly enforced federal, state and foreign regulations. Furthermore, if microbial, viral or other contaminations are discovered in our products or in the manufacturing facilities in which our products are made, such manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination.
All of our XmAb engineered antibodies are manufactured by starting with cells which are stored in a cell bank. We have one master cell bank for each antibody manufactured in accordance with cGMP and multiple working cell banks and believe we would have adequate backup should any cell bank be lost in a catastrophic event. However, it is possible that we could lose multiple cell banks and have our manufacturing severely impacted by the need to replace the cell banks.
30
We cannot assure you that any stability or other issues relating to the manufacture of any of our product candidates or products will not occur in the future. Additionally, our manufacturer may experience manufacturing difficulties due to resource constraints or as a result of labor disputes or unstable political environments. If our manufacturers were to encounter any of these difficulties, or otherwise fail to comply with their contractual obligations, our ability to provide any product candidates to patients in clinical trials and products to patients, once approved, would be jeopardized. Any delay or interruption in the supply of clinical trial supplies could delay the completion of clinical trials, increase the costs associated with maintaining clinical trial programs and, depending upon the period of delay, require us to commence new clinical trials at additional expense or terminate clinical trials completely. Any adverse developments affecting clinical or commercial manufacturing of our product candidates or products may result in shipment delays, inventory shortages, lot failures, product withdrawals or recalls, or other interruptions in the supply of our product candidates or products. We may also have to take inventory write‑offswrite-offs and incur other charges and expenses for product candidates or products that fail to meet specifications, undertake costly remediation efforts or seek more costly manufacturing alternatives. Accordingly, failures or difficulties faced at any level of our supply chain could
41
materially adversely affect our business and delay or impede the development and commercialization of any of our product candidates or products and could have a material adverse effect on our business, prospects, financial condition and results of operations.
Adverse side effects or other safety risks associated with our product candidates could delay or preclude approval, cause us to suspend or discontinue clinical trials, abandon product candidates, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any.
Undesirable side effects caused by our product candidates could result in the delay, suspension or termination of clinical trials by us, our collaborators, the FDA or other regulatory authorities for a number of reasons. If we elect or are required to delay, suspend or terminate any clinical trial of any product candidates that we develop, the commercial prospects of such product candidates will be harmed and our ability to generate product revenues from any of these product candidates will be delayed or eliminated. Serious adverse events observed in clinical trials could hinder or prevent market acceptance of the product candidate at issue. Any of these occurrences may harm our business, prospects, financial condition and results of operations significantly.
In February 2019, we received notice from the FDA placing the XmAb14045 study on partial clinical hold due to safety issues of cytokine release syndrome (CRS) and pulmonary toxicities. Under the partial hold, existing subjects on the trial may continue to receive dosing; however, no new subjects may be enrolled pending FDA review of a clinical hold response.
The partial clinical hold was initiated following recent safety reports Xencor submitted to the FDA on two patients deaths that were considered at least possibly related to XmAb14045. One patient experienced cytokine release syndrome (CRS) after their first dose, the treatment of which was complicated by the patient’s decision to withdraw care. Once subject developed acute pulmonary edema following several doses of XmAb14045. Items to be addressed in the response include analysis of CRS cases per dosing level, efficacy information, and strategies to mitigate the observed toxicities.
Previously, we observed CRS as a toxicity in 55% of total patients dosed (36) with 6% of patients experiencing Grade 3 or Grade 4 CRS. Additional adverse events consistent with CRS but not reported as such, include chills, fever, tachycardia, hypotension and hypertension within 24 hours of infusion, were reported in an additional 29% of patients (19).
31
In our Phase 1b/2a clinical trial of XmAb5871, some subjects reported mild to moderate gastrointestinal toxicities (nausea, vomiting and diarrhea). Other treatment related adverse events experienced in more than two XmAb5871-treated patients were pyrexia (fever) and headache. Treatment related serious adverse events occurred in two patients that received XmAb5871: infusion related reaction and venous thrombosis. Further, in our Phase 1a clinical trial of XmAb7195 resulted in subjects having urticaria and dose limiting thrombocytopenia. If these or other side effects cause excessive discomfort, safety risks or reduction in acceptable dosage, then the development and commercialization of XmAb5871 or XmAb7195 could suffer significant negative consequences. We cannot predict if additional types of adverse events or more serious adverse events will be observed in future clinical trials of XmAb5871, XmAb7195 or any future product candidate.
In addition, we observed detectable levels of immunogenicity, or the creation by the immune system of anti‑XmAb5871 antibodies, in 44% of subjects receiving XmAb5871 in the Phase 1a clinical trial. While a common occurrence for antibody therapies, immunogenicity to XmAb5871 or any of our other product candidates could neutralize the therapeutic effects of XmAb5871 or such other candidates and/or alter their pharmacokinetics, which could have a material adverse effect on the effectiveness of our product candidates and on our ability to commercialize them.
We may not be successful in our efforts to use and expand our XmAb technology platform to build a pipeline of product candidates and develop marketable products.
We are using our proprietary XmAb technology platform to develop engineered antibodies, with an initial focus on four properties: immune inhibition, cytotoxicity, extended half‑life and most recently, heterodimeric Fc domains enabling molecules with dual target binding. This platform has led to our current pipeline of candidates as well as the other programs that utilize our technology and that are being developed by our partners and licensees. While we believe our preclinical and clinical data to date, together with our established partnerships, has validated our platform to a degree, we are at a very early stage of development. Although the first drug candidate incorporating our Fc technology has been approved by the FDA, other drug candidates that incorporate our Fc technologies or Fc candidates have not yet, and may never lead to, approved or marketable therapeutic antibody products. Even if we are successful in continuing to build our pipeline, the potential product candidates that we identify may not be suitable for clinical development, including as a result of their harmful side effects, limited efficacy or other characteristics that indicate that they are unlikely to be products that will receive marketing approval and achieve market acceptance. If we do not successfully develop and commercialize product candidates based upon our technological approach, we may not be able to obtain product or partnership revenues in future periods, which would adversely affect our business, prospects, financial condition and results of operations.
We face significant 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. We have competitors both in the United States and internationally, including major multinational pharmaceutical companies, biotechnology companies, universities and other research institutions. Many of our competitors have substantially greater financial, technical and other resources, such as larger research and development staff and experienced marketing and manufacturing organizations and well‑established sales forces. Competition may increase further as a result of advances in the commercial applicability of technologies and greater availability of capital for investment in these industries. Our competitors may succeed in developing, acquiring or licensing on an exclusive basis, drug products that are more effective or less costly than any product candidate that we are currently developing or that we may develop.
32
We face intense competition in autoimmune disease drug development from multiple monoclonal antibodies, other biologics and small molecules approved for the treatment of autoimmune diseases many of which are being developed or marketed by large multinational pharmaceutical companies. GlaxoSmithKline’s Benlysta (belimumab) is currently the only monoclonal antibody that we are aware of that is approved for the treatment of lupus although we believe that Biogen Idec/Genentech’s Rituxan (rituximab) is prescribed, off label, for this indication. There is also no approved therapy for IgG4-RD but we believe Rituxan is prescribed, off label. In addition, these and other pharmaceutical companies have monoclonal antibodies or other biologics in clinical development for the treatment of autoimmune diseases.
Many companies have approved therapies or are developing drugs for the treatment of asthma including multinational pharmaceutical companies such as GlaxoSmithKline, Roche/Genentech, Novartis and AstraZeneca plc. Genentech’s and Novartis’ Xolair is currently the only monoclonal antibody targeting IgE that we are aware of that is approved for the treatment of severe asthma. Three other monoclonal antibodies, Nucala, Cinquair and Fasenra have recently been approved for treatment of severe asthma.
Competition in blood cancer drug development is intense, with more than 250 compounds in clinical trials by large multinational pharmaceutical companies and Rituxan is just one of many monoclonal antibodies approved for the treatment of non‑Hodgkin lymphomas or other blood cancers. Both Roche and Regeneron have bispecific CD20 drug candidates in Phase 1 of development and there are many other companies developing their own bispecific platform technologies and drug candidates. MacroGenics has a bispecific CD123 x CD3 antibody currently in Phase 1 and Janssen has a CD123 x CD3 bispecific antibody that is also currently in Phase 1.
Our ability to compete successfully will depend largely on our ability to leverage our experience in drug discovery and development to:
|
|
|
|
|
|
|
|
|
|
The availability and price of our competitors’ products could limit the demand, and the price we are able to charge, for any of our product candidates, if approved. We will not achieve our business plan if acceptance is inhibited by price competition or the reluctance of physicians to switch from existing drug products to our products, or if physicians switch to other new drug products or choose to reserve our products for use in limited circumstances.
Established biopharmaceutical companies may invest heavily to accelerate discovery and development of products that could make our product candidates less competitive. In addition, any new product that competes with an approved product must demonstrate compelling advantages in efficacy, convenience, tolerability and safety in order to overcome price competition and to be commercially successful. Accordingly, our competitors may succeed in obtaining patent protection, receiving FDA approval or discovering, developing and commercializing medicines before we do, which would have a material adverse impact on our business. We will not be able to successfully commercialize our product candidates without establishing sales and marketing capabilities internally or through collaborators.
33
Our current and future relationships with healthcare professionals, principal investigators, consultants, customers and third-party payors in the United States and elsewhere may be subject, directly or indirectly, to applicable anti-kickback, fraud and abuse, false claims, physician payment transparency, health information privacy and security and other healthcare laws and regulations, which could expose us to penalties.
Healthcare providers, physicians and third-party payors in the United States and elsewhere will play a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval. Our current and future arrangements with healthcare professionals, principal investigators, consultants, customers and third-party payors may expose us to broadly applicable fraud and abuse and other healthcare laws, including, without limitation, the federal Anti-Kickback Statute and the federal civil False Claims Act, that may constrain the business or financial arrangements and relationships through which we sell, market and distribute any product candidates for which we obtain marketing approval. In addition, we may be subject to physician payment transparency laws and patient privacy and security regulation by the federal government and by the states and foreign jurisdictions in which we conduct our business. The applicable federal, state and foreign healthcare laws that may affect our ability to operate include the following:
|
|
|
|
|
|
|
|
|
|
34
|
|
|
|
Further, the Affordable Care Act, among other things, amended the intent requirement of the federal Anti-Kickback Statute and the healthcare fraud statute. 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. In addition, the Affordable Care Act provided 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 federal civil False Claims Act.
Efforts to ensure that our future business arrangements with third parties will comply with applicable healthcare laws and regulations may involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, including, without limitation, damages, fines, imprisonment, disgorgement, exclusion from participation in government healthcare programs, such as Medicare and Medicaid, additional reporting requirements and/or oversight if we become 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, as well as reputational harm, which could significantly harm our business.
Recently enacted and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and affect the prices we may obtain.
Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives. In March 2010, President Obama signed into law the Affordable Care Act, a sweeping law 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.
35
The Affordable Care Act established an annual, nondeductible fee on any entity that manufactures or imports certain specified branded prescription drugs and biologic agents, 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, increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program, extended the Medicaid Drug Rebate program to utilization of prescriptions of individuals enrolled in Medicaid managed care organizations, and provided incentives to programs that increase the federal government’s comparative effectiveness research. In addition, the Affordable Care Act implemented payment system reforms including a national pilot program on payment bundling to encourage hospitals, physicians and other providers to improve the coordination, quality and efficiency of certain healthcare services through bundled payment models.
There have been judicial and Congressional challenges to certain aspects of the Affordable Care Act, as well as recent efforts by the Trump administration to repeal or replace certain aspects of the Affordable Care Act. Since January 2017, President Trump has signed two Executive Orders and other directives designed to delay the implementation of certain provisions of the Affordable Care Act or otherwise circumvent some of the requirements for health insurance mandated by the Affordable Care Act. Concurrently, Congress has considered legislation that would repeal or repeal and replace all or part of the Affordable Care Act. While Congress has not passed comprehensive repeal legislation, two bills affecting the implementation of certain taxes under the Affordable Care Act have been signed into law. Legislation enacted in 2017, informally titled the Tax Cuts and Jobs Act of 2017 (TCJA), includes a provision which repealed, effective January 1, 2019, 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 January 22, 2018, President Trump signed a continuing resolution on appropriations for fiscal year 2018 that delayed the implementation of certain Affordable Care Act-mandated fees, including the so-called “Cadillac” tax on certain high cost employer-sponsored insurance plans, the annual fee imposed on certain health insurance providers based on market share, and the medical device excise tax on non-exempt medical devices. The Bipartisan Budget Act of 2018 (BBA) among other things, amended the Affordable Care Act, effective January 1, 2019, to increase from 50 percent to 70 percent the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part D and to close the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole”.In July 2018, the Centers for Medicare & Medicaid Services (CMS) published a final rule permitting further collections and payments to and from certain Affordable Care Act qualified health plans and health insurance issuers under the Affordable Care Act risk adjustment program in response to the outcome of federal district court litigation regarding the method CMS uses to determine this risk adjustment. On December 14, 2018, a Texas U.S. District Court Judge ruled that the Affordable Care Act is unconstitutional in its entirety because the “individual mandate” was repealed by Congress as part of the TCJA. While the Texas U.S. District Court Judge, as well as the Trump administration and CMS, have stated that the ruling will have no immediate effect pending appeal of the decision, it is unclear how this decision, subsequent appeals, and other efforts to repeal and replace the Affordable Care Act will impact the Affordable Care Act and our business.
In addition, other legislative changes have been proposed and adopted since the Affordable Care Act was enacted. On August 2, 2011, President Obama signed into law the Budget Control Act of 2011, which, among other things, created the Joint Select Committee on Deficit Reduction to recommend to Congress proposals in spending reductions. The Joint Select Committee did not achieve a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, triggering the legislation’s automatic reduction to several government programs. This includes reductions to Medicare payments to providers of 2% per fiscal year, which went into effect on April 1, 2013 and, due to subsequent legislation, including the BBA, will remain in effect through 2027 unless additional Congressional action is taken. 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, imaging centers and cancer treatment centers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.
36
Further, there has been heightened governmental scrutiny recently over the manner in which manufacturers set prices for their marketed products, which have resulted in several 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, reduce the cost of products under Medicare, and reform government program reimbursement methodologies for products. At the federal level, the Trump administration’s budget proposal for fiscal year 2019 contains further price control measures that could be enacted during the 2019 budget process or in other future legislation, including, for example, measures to permit Medicare Part D plans to negotiate the price of certain products under Medicare Part B, to allow some states to negotiate product prices under Medicaid, and to eliminate cost sharing for generics for low-income patients. Additionally, the Trump administration released a “Blueprint” to lower drug prices and reduce out of pocket costs of drugs that contains additional proposals to increase manufacturer competition, increase the negotiating power of certain federal healthcare programs, incentivize manufacturers to lower the list price of their products and reduce the out of pocket costs of drug products paid by consumers. HHS has already started the process of soliciting feedback on some of these measures and, at the same, is immediately implementing others under its existing authority. For example, in September 2018, CMS announced that it will allow Medicare Advantage Plans the option to use step therapy for Part B drugs beginning January 1, 2019, and in October 2018, HHS through CMS proposed a new rule that would require direct-to-consumer television advertisements of prescription drugs and biological products, for which payment is available through or under Medicare or Medicaid, to include in the advertisement the Wholesale Acquisition Cost, or list price, of that drug or biological product. On January 31, 2019, the HHS Office of Inspector General proposed modifications to the federal Anti-Kickback Statute discount safe harbor for the purpose of reducing the cost of drug products to consumers which, among other things, if finalized, will affect discounts paid by manufacturers to Medicare Part D plans, Medicaid managed care organizations and pharmacy benefit managers working with these organizations. While some of these and other proposed measures may require additional authorization to become effective, Congress and the Trump administration have each indicated that it will continue to seek new legislative and/or administrative measures to control pharmaceutical costs. At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological 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, designed to encourage importation from other countries and bulk purchasing. We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our products or additional pricing pressure.
Additionally, on May 30, 2018, the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 (the Right to Try Act) was signed into law. The law, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase 1 clinical trial and that are undergoing investigation for FDA approval. Under certain circumstances, eligible patients can seek treatment without enrolling in clinical trials and without obtaining FDA permission under the FDA expanded access program. There is no obligation for a pharmaceutical manufacturer to make its drug products available to eligible patients as a result of the Right to Try Act.
We expect that healthcare reform measures that may be adopted in the future may result in more rigorous coverage criteria and lower reimbursement, and in additional downward pressure on the price that may be charged for any of our product candidates, if approved.
37
Even if we are able to commercialize any product candidates, our product candidates may be subject to unfavorable pricing regulations, third-party coverage and reimbursement policies or healthcare reform initiatives.
Our ability to commercialize any product candidates successfully will depend, in part, on the extent to which coverage and adequate reimbursement for our product candidates will be available from government payor programs at the federal and state levels, including Medicare and Medicaid, private health insurers, managed care plans and other third-party payors. Government authorities and other third-party payors, such as private health insurers and health maintenance organizations, decide which medical products they will pay for and establish reimbursement levels. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for products. Coverage and reimbursement may not be available for any product that we commercialize and, even if these are available, the level of reimbursement may not be satisfactory. Inadequate reimbursement levels may adversely affect the demand for, or the price of, any product candidate for which we obtain marketing approval. Obtaining and maintaining adequate reimbursement for our drugs may be difficult. We may be required to conduct expensive pharmacoeconomic studies to justify coverage and reimbursement or the level of reimbursement compared to other therapies. If coverage and adequate reimbursement are not available or reimbursement is available only to limited levels, we may not be able to successfully commercialize any product candidates for which marketing approval is obtained.
In addition, net prices for products may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of products 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 policies. 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 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 no assurance that coverage and adequate reimbursement will be applied consistently or obtained at all. Further, there may be significant delays in obtaining coverage and reimbursement for newly approved products, and coverage may be more limited than the indications for which the product is approved by the FDA or similar regulatory authorities outside the United States. Moreover, eligibility for coverage and reimbursement does not imply that a product will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution expenses. Interim reimbursement levels for new products, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Our inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for any approved products that we develop could significantly harm our operating results, our ability to raise capital needed to commercialize products and our overall financial condition.
The regulations that govern marketing approvals, pricing, coverage and reimbursement for new drugs and biological products vary widely from country to country. Current and future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. Some countries require approval of the sale price of a product 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 in a particular country, but then be subject to price regulations that delay commercial launch of the product, possibly for lengthy time periods, and negatively impact the revenues able to be generated from the sale of the product in that country. Adverse pricing limitations may hinder our ability to recoup our investment in one or more product candidates, even if our product candidates obtain marketing approval.
There can be no assurance that our product candidates, if they are approved for sale in the United States or in other countries, will be considered medically reasonable and necessary for a specific indication, that they will be considered cost-effective by third-party payors, that coverage or an adequate level of reimbursement will be available, or that third-party payors’ reimbursement policies will not adversely affect our ability to sell our product candidates profitably if they are approved for sale.
38
Our business could be negatively impacted by cyber security threats.
In the ordinary course of our business, we use our data centers and our networks to store and access our proprietary business information. We face various cyber security threats, including cyber security attacks to our information technology infrastructure and attempts by others to gain access to our proprietary or sensitive information. The procedures and controls we use to monitor these threats and mitigate our exposure may not be sufficient to prevent cyber security incidents. The result of these incidents could include disrupted operations, lost opportunities, misstated financial data, liability for stolen assets or information, increased costs arising from the implementation of additional security protective measures, litigation and reputational damage. Any remedial costs or other liabilities related to cyber security incidents may not be fully insured or indemnified by other means.
Risks Relating to Our Dependence on Third Parties
Our existing partnerships are important to our business, and future partnerships may also be important to us. If we are unable to maintain any of these partnerships, or if these partnerships are not successful, our business could be adversely affected.
Because developing biologics products, conducting clinical trials, obtaining regulatory approval, establishing manufacturing capabilities and marketing approved products are expensive, we have entered into partnerships, and may seek to enter into additional partnerships, with companies that have more resources and experience than us, and we may become dependent upon the establishment and successful implementation of partnership agreements.
Our partnership and license agreements include those we have announced with Janssen Genentech, Novartis, Amgen, MorphoSys, Alexion and others. These partnerships and license agreements also have provided us with important funding for our development programs, and we expect to receive additional funding under these partnerships in the future. Our existing partnerships, and any future partnerships we enter into, may pose a number of risks, including the following:
1. | collaborators have significant discretion in determining the efforts and resources that they will apply to these partnerships. |
2. | our |
3. | our |
4. |
|
| collaborators may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities; |
| collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; |
39
| collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours, which may cause collaborators to cease to devote resources to the commercialization of our product candidates; |
| a collaborator with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products; |
42
| disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development, might cause delays or termination of the research, development or commercialization of product candidates, might lead to additional responsibilities for us with respect to product candidates, or might result in litigation or arbitration, any of which would be |
| while we have generally retained the right to maintain and defend our intellectual property under our agreements with collaborators, certain collaborators may not properly maintain or defend certain of our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information; |
| collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; |
| collaborators may learn about our technology and use this knowledge to compete with us in the future; |
| results of collaborators’ preclinical or clinical studies could produce results that harm or impair other products using our XmAb technology platform; |
| there may be conflicts between different collaborators that could negatively affect those partnerships and potentially others; and |
| the number and type of our partnerships could adversely affect our attractiveness to future collaborators or acquirers. |
If our partnerships and license agreements do not result in the successful development and commercialization of products or if one of our collaborators terminates its agreement with us, we may not receive any future research and development funding or milestone or royalty payments under the arrangement. If we do not receive the funding we expect under these arrangements, our continued development of our product candidates could be delayed, and we may need additional resources to develop additional product candidates. All of the risks described in these risk factors relating to product development, regulatory approval and commercialization described in this Annual Report also apply to the activities of our collaborators and there can be no assurance that our partnerships and license agreements will produce positive results or successful products on a timely basis or at all.
Our partnership agreements generally grant our collaborators exclusive rights under certain of our intellectual property and may therefore preclude us from entering into partnerships with others relating to the same or similar compounds, indications or diseases. In addition, partnership agreements may place restrictions or additional obligations on our ability to license additional compounds in different indications, diseases or geographical locations. If we fail to comply with or breach any provision of a partnership agreement, a collaborator may have the right to terminate, in whole or in part, such agreement or to seek damages. Many of our collaborators also have the right to terminate the partnership agreement for convenience. If a partnership agreement is terminated, in whole or in part, we may be unable to continue the development and commercialization of the applicable product candidates, and even if we are able to do so, such efforts may be delayed and result in additional costs.
40
There is no assurance that a collaborator who is acquired by a third party would not attempt to change certain contract provisions that could negatively affect our partnership. The acquiring company may also not accept the terms or assignment of our contracts and may seek to terminate the agreements. Any one of our partners could breach covenants, restrictions and/or sub‑licensesub-license agreement provisions leading us into disputes and potential breaches of our agreements with other partners.
We may in the future determine to partner with additional pharmaceutical and biotechnology companies for development and potential commercialization of therapeutic products. We face significant competition in seeking appropriate collaborators. Our ability to reach a definitive agreement for a partnership will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed partnership
43
and the proposed collaborator’s evaluation of a number of factors. If we elect to fund and undertake development or commercialization activities on our own, we may need to obtain additional expertise and additional capital, which may not be available to us on acceptable terms or at all. If we fail to enter into partnerships and do not have sufficient funds or expertise to undertake the necessary development and commercialization activities, we may not be able to further develop our product candidates or bring them to market or continue to develop our product platform and our business, prospects, financial condition and results of operations may be materially and adversely affected.
We rely upon third‑partythird-party contractors, and service providers for the execution of most aspects of our development programs. Failure of these collaborators to provide services of a suitable quality and within acceptable timeframes may cause the delay or failure of our development programs.
We outsource manufacturing, certain functions, teststesting and services to contract research organizations (CROs), medical institutions and collaborators, as well as outsourcing manufacturing to collaborators and/or contract manufacturers, and we rely on third parties for quality assurance, clinical monitoring, clinical data management and regulatory expertise. We also have engaged, and may in the future engage, a CRO to run all aspects of a clinical trial on our behalf. There is no assurance that such individuals or organizations will be able to provide the functions, tests, biologic supply or services as agreed upon or in a quality fashion and we could suffer significant delays in the development of our products or processes.
In some cases, there may be only one or few providers of such services, including clinical data management or manufacturing services. In addition, the cost of such services could be significantly increased over time. We rely on third parties and collaborators as mentioned above to enroll qualified patients and conduct, supervise and monitor our clinical trials. Our reliance on these third parties and collaborators for clinical development activities reduces our control over these activities. Our reliance on these parties, however, does not relieve us of our regulatory responsibilities, including ensuring that our clinical trials are conducted in accordance with GCP regulations and the investigational plan and protocols contained in the regulatory agency applications. In addition, these third parties may not complete activities on schedule or may not manufacture under GMP conditions. Preclinical or clinical studies may not be performed or completed in accordance with Good Laboratory Practices (GLP) regulatory requirements or our trial design. If these third parties or collaborators do not successfully carry out their contractual duties or meet expected deadlines, obtaining regulatory approval for manufacturing and commercialization of our product candidates may be delayed or prevented. We rely substantially on third‑partythird-party data managers for our clinical trial data. There is no assurance that these third parties will not make errors in the design, management or retention of our data or data systems. There is no assurance these third parties will pass FDA or regulatory audits, which could delay or prohibit regulatory approval.
41
We rely on third parties to manufacture supplies of our preclinical and clinical product candidates. The development of such candidates could be stopped or delayed if any such third party fails to provide us with sufficient quantities of product or fails to do so at acceptable quality levels or prices or fails to maintain or achieve satisfactory regulatory compliance.
We do not currently have nor do we plan to acquire the infrastructure or capability internally to manufacture our clinical drug supplies for use in the conduct of our clinical trials, and we lack the resources and the capability to manufacture any clinical candidates on a clinical scale. Instead, we rely on our third‑partythird-party manufacturing partners Fuji, to produce XmAb5871 and third parties for fill and testing services, and we rely on KBI to producemanufacture our bispecific Fc development candidates.clinical drug supply. Any of our contract manufacturers may not perform as agreed, may be unable to comply with cGMP requirements and with FDA, state and foreign regulatory requirements or may terminate their respective agreements with us.
In addition, manufacturers are subject to ongoing periodic unannounced inspection by the FDA and other governmental authorities to ensure strict compliance with government regulations. We do not control the manufacturing processes of KBI or Fuji and are currently completely dependent on KBI and Fuji for the production of XmAb5871, XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104, and XmAb24306 in accordance with cGMP,our third-party manufacturing partners, which include, among other things, quality control, quality assurance and the maintenance of records and documentation. If we were to experience an unexpected loss of supply, we could experience delays in our planned clinical trials as KBI or Fujiour third-party manufacturing partner would need to manufacture additional clinical drug supply and would need sufficient lead time to schedule a manufacturing slot. While there are other potential suppliers of clinical supplies of our biologics, the long transition periods necessary to switch manufacturers for any of XmAb5871, XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104, and XmAb24306our clinical drug supply would significantly delay our clinical trials and the commercialization of such products, if approved.
We intend44
Risks Related To Our Industry
Clinical trials are expensive and take years to rely on third partiesconduct and the outcome of such clinical trials is uncertain. Clinical trials may fail to manufacture commercial supplies ofprove our product candidate. If wecandidates are unablesafe and effective. This could lead to enter into commercial supply agreements with third‑party suppliersdelays, downsizing or if any such third‑party supplier fails to provide us with sufficient quantities or fails to comply with regulatory requirements, commercialization of such products could be delayed or stopped.
We do not currently have nor do we plan to acquire the infrastructure or capability internally to manufacture our products on a commercial scale. Although we have entered into agreements for the manufacturetermination of clinical suppliesdevelopment plans for any our product candidates.
Each product candidate must receive regulatory approval and therefore must undergo rigorous and extensive preclinical studies and clinical trials to demonstrate safety and efficacy in patients. Clinical trials at any stage in development may fail to demonstrate the safety, efficacy or pharmacologic properties needed to be a viable product candidate in patients. Early clinical trials may fail to demonstrate the safety and pharmacokinetic characteristics needed to invest in larger later stage clinical studies. Later clinical studies that are larger may not demonstrate the desired safety and efficacy profile needed to be of XmAb5871, XmAb7195, XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104,benefit to patients. Additionally, regulatory authorities may determine that the data provided is not sufficient to grant marketing approval for our product candidates and XmAb24306 we have not entered into a commercial supply agreement with KBI or FUJI. Further, KBI has not demonstrated that it will be capable of manufacturing XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104, and XmAb24306 on a large commercial scale. We might be unable to identify manufacturers for late stagemay request additional data including additional clinical trials or commercial supply on acceptable termsreject product approval.
Adverse side effects or at all. A change to the manufacturing process for any ofother safety risks associated with our product candidates wouldcould delay or preclude approval, cause us to incursuspend or discontinue clinical trials, abandon product candidates, limit the commercial profile of an approved label, or result in significant costsnegative consequences following marketing approval, if any.
Conducting early clinical trials is complex and the outcomes are uncertain. Preclinical studies are performed to devote significant efforts to implement such a change. Additionally,help inform human clinical trials, but human and animal studies are not comparable. Expected or unexpected undesirable side effects caused by our product candidates could result in the late‑stagedelay, suspension or termination of clinical development and commercialization of XmAb5871trials by us, our collaborators, the FDA or other product candidates by usregulatory authorities for a number of reasons. If we elect or our collaborators may be delayed as a result, which would materially and adversely affect our business.
42
If our third‑party manufacturers cannot successfully manufacture material that conforms to our specifications and the applicable regulatory authorities’ strict regulatory requirements, or pass regulatory inspection, they will not be able to secure or maintain regulatory approval for the manufacturing facilities. In addition, we have no control over the ability of any third‑party manufacturer to maintain adequate quality control, quality assurance and qualified personnel. The facilities used by our third‑party manufacturers to manufacture XmAb5871, XmAb7195, XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104, XmAb24306 and any other potential product candidates that we may develop, in the future must be approved by the applicable regulatory authorities, including the FDA, pursuant to inspections thatcommercial prospects of such product candidates will be conducted after we submit our BLA to the FDA. In addition, manufacturers are subject to ongoing periodic unannounced inspection by the FDAharmed and other governmental authorities to ensure strict compliance with government regulations. If the FDA or any other applicable regulatory authorities do not approve these facilities for the manufacture of our products or if they withdraw any such approval in the future, or if our suppliers or third‑party manufacturer decide they no longer want to supply our biologics or manufacture our products, we may need to find alternative manufacturing facilities, which would significantly impact our ability to generate product revenues from any of these product candidates will be delayed or eliminated. Serious adverse events observed in clinical trials could hinder or prevent market our products andacceptance of the product candidate at issue. Any of these occurrences may harm our business, prospects, financial condition and results of operations may be materially and adversely affected.significantly.
Risks Relating to Our Intellectual Property
If we are unable to obtain, maintain and enforce intellectual property protection covering our products, others may be able to make, useexperience delays or sell products substantially the same as ours, which could adversely affect our ability to competedifficulties in the market.
Our commercial success depends,enrollment of patients in part, onclinical trials, our ability to obtain, maintain and enforce patents, trade secrets, trademarks and other intellectual property rights and to operate without having third parties infringe, misappropriate or circumvent the rights that we own or license. The valuereceipt of many of our partnered licensing arrangements is based on the underlying intellectual property and related patents. If we are unable to obtain, maintain and enforce intellectual property protection covering our products or underlying technologies, others may be able to make, use or sell products that are substantially the same as ours without incurring the sizeable development and licensing costs that we have incurred, which would adversely affect our ability to compete in the market. As of December 31, 2018, we held over 750 issued patents and pending patent applications. We file patent applications in the United States, Canada, Japan, Europe and other major markets either directly or via the Patent Cooperation Treaty. Our ability to stop third parties from making, using, selling, offering to sell or importing our product candidates is dependent upon the extent to which we have rights under valid and enforceable patents or trade secrets that cover these activities. However, the patent positions of biopharmaceutical companies, including ours, can be highly uncertain and involve complex legal and factual questions for which important legal principles remain unresolved. No consistent policy regarding the breadth of claims allowed in patents in these fields has emerged to date in the United States. The U.S. patent laws have recently changed, there have been changes regarding how patent laws are interpreted, and the U.S. Patent and Trademark Office (the PTO) has also implemented changes to the patent system. Some of these changes are currently being litigated, and we cannot accurately determine the outcome of any such proceedings or predict future changes in the interpretation of patent laws or changes to patent laws which might be enacted into law. Those changes may materially affect our patents, our ability to obtain patents or the patents and applications of our collaborators and licensors. The patent situation in the biopharmaceutical industry outside the United States is even more uncertain. Therefore, there is no assurance that our pending patent applications will result in the issuance of patents or that we will develop additional proprietary products which are patentable. Moreover, patents issued or to be issued to us may not provide us with any competitive advantage. Our patent position is subject to numerous additional risks, including the following:
|
|
|
|
|
|
|
|
43
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Any of these factors could hurt our ability to gain full patent protection for our products. Registered trademarks and trademark applications in the United States and other countries are subject to similar risks as described above for patents and patent applications, in addition to the risks described below.
44
Many of our product development partnership agreements are complex and may call for licensing or cross‑licensing of potentially blocking patents, know‑how or intellectual property. Due to the potential overlap of data, know‑how and intellectual property rights there can be no assurance that one of our collaborators will not dispute our right to use, license or distribute data, know‑how or other intellectual property rights, and this may potentially lead to disputes, liability or termination of a program. There are no assurances that our actions or the actions of our collaborators would not lead to disputes or cause us to default with other collaborators. For example, we may become involved in disputes with our collaborators relating to the ownership of intellectual property developed in the course of the partnership. We also cannot be certain that a collaborator will not challenge the validity or enforceability of the patents we license.
We cannot be certain that any country’s patent and/or trademark office will not implement new rules which could seriously affect how we draft, file, prosecute and/or maintain patents, trademarks and patent and trademark applications. We cannot be certain that increasing costs for drafting, filing, prosecuting and maintaining patents, trademarks and patent and trademark applications will not restrict our ability to file for patent protection. For example, we may elect not to seek patent protection in certain jurisdictions or for certain inventions in order to save costs. We may be forced to abandon or return the rights to specific patents due to a lack of financial resources.
We currently rely, and may in the future rely, on certain intellectual property rights licensed from third parties to protect our technology and certain product candidates. We have licensed and sublicensed certain intellectual property relating to our Xtend technology from a third party. We have also sublicensed certain intellectual property rights related to our bispecific technology from a third party and, we have licensed certain intellectual property rights from a third party related to our XmAb18087 product candidate. We also license certain rights to the underlying cell lines for all our product candidates from third parties. Under these licenses, we have no right to control patent prosecution of the intellectual property or to enforce the patents, and as such the licensed rights may not be adequately maintained by the licensors. The termination of these or other licenses could also prevent us from commercializing product candidates covered by the licensed intellectual property.
Furthermore, the research resulting in the in‑licensed patents was developed in the course of research funded by the U.S. government. As a result, the U.S. government may have certain rights (“march‑in rights”) to intellectual property embodied in our Xtend products. Government rights in certain inventions developed under a government‑funded program include a non‑exclusive, non‑transferable, irrevocable worldwide license to use inventions for any governmental purpose. Circumstances that trigger march‑in rights include, for example, failure to take, within a reasonable time, effective steps to achieve practical application of the invention in a field of use, failure to satisfy the health and safety needs of the public and failure to meet requirements of public use specified by federal regulations. Federal law requires any licensor of an invention that was partially funded by the federal government to obtain a covenant from any exclusive licensee to manufacture products using the invention substantially in the United States. The U.S. government also has the right to use and disclose, without limitation, scientific data relating to licensed technology that was developed in whole or in part at government expense. The government funding agency can elect to exercise these march‑in rights on their own initiative or at the request of a third party. It is also possible that we might knowingly or unknowingly in-license additional technology that is subject to U.S. government march-in rights.
We intend to file applications for trademark registrations in connection with our product candidates in various jurisdictions, including the United States. No assurance can be given that any of our trademark applications will be registered in the United States or elsewhere, or that the use of any registered or unregistered trademarks will confer a competitive advantage in the marketplace. Furthermore, even if we are successful in our trademark registrations, the FDA andnecessary regulatory authorities in other countries have their own process for drug nomenclature and their own views concerning appropriate proprietary names. No assurance can be given that the FDA or any other regulatory authority will approve of any of our trademarks or will not request reconsideration of one of our trademarks at some time in the future. The loss, abandonment, or cancellation of any of our trademarks or trademark applications could negatively affect the success of the product candidates to which they relate.
45
If we are not able to prevent disclosure of our trade secrets and other proprietary information, the value of our technology and productsapprovals could be significantly diminished.delayed or prevented.
We rely on trade secret protection to protect our interests in proprietary know‑how and in processes for which patents are difficult to obtain or enforce. We may not be able to protectinitiate or continue clinical trials for our trade secrets adequately.product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials as required by the FDA or similar regulatory authorities outside the United States. In addition, some of our competitors have ongoing clinical trials for product candidates that treat the same indications as our product candidates, and patients who would otherwise be eligible for our clinical trials may instead enroll in clinical trials of our competitors’ product candidates.
Our inability to enroll a sufficient number of patients for any of our clinical trials could result in significant delays and could require us to abandon one or more clinical trials altogether. Enrollment delays in our clinical trials may result in increased development costs for our product candidates and in delays to commercially launching our product candidates, if approved, which would cause the value of our company to decline and limit our ability to obtain additional financing.
Our industry is subject to competition for skilled personnel and the challenges we face to identify and retain key personnel could impair our ability to effectively conduct and grow our operations.
Attracting and retaining the highly qualified management, scientific and medical personnel necessary for us to successfully implement our business strategy is extremely competitive in the biotechnology industry. Our industry is experiencing an increasing rate of competition in hiring and retaining employees and in turnover of management personnel. We depend heavily on our current management team, whose services are critical to the successful implementation of our product candidate development and regulatory strategies. In order to induce valuable employees to continue their employment with us, we have a policyprovided equity incentives that vest over time. The value to employees of requiring
45
this equity is significantly affected by movements in our consultants, advisorsstock price that are beyond our control and collaboratorsmay at any time be insufficient to enter into confidentiality agreementscounteract more lucrative offers from other companies.
Despite our efforts to retain valuable employees, members of our management team may terminate their employment with us at any time, with or without notice. Further, we do not maintain “key person” insurance for any of our executives or other employees. The loss of the services of any of our executive officers and our inability to find suitable replacements could harm our business, financial condition, prospects and ability to achieve the successful development or commercialization of our product candidates. Our success also depends on our ability to continue to attract, retain and motivate highly skilled scientific and medical personnel at all levels.
Since 2016 we have been increasing the number of our employees and expanding the scope of our operations with a goal of advancing multiple clinical candidates into development. The increase in our number of employees places a significant strain on our management, operations, and financial resources, and we may have difficulty managing this growth. As we continue to entergrow our operations and advance our clinical programs into invention, non‑disclosurelater stages of development, it will require us to recruit and non‑retain employees with additional knowledge and skill sets and no assurance can be provided that we will be able to attract employees with the necessary skill set to assist in our growth. Many of the other biotechnology and pharmaceutical companies and academic institutions that we compete agreements. However,against for qualified personnel have greater financial and other resources, different risk profiles and a longer history in the industry than we do. We also may employ consultants or part-time and contract employees. There can be no assurance that these individuals are retainable. While we have been able to attract and retain skilled and experienced personnel and consultants in the past, no assurance can be given that we have entered into appropriate agreements with all parties that have had accesswill be able to our trade secrets, know‑how or other proprietary information. There is also no assurance that such agreements will provide for a meaningful protection of our trade secrets, know‑how or other proprietary informationdo so in the eventfuture.
The development and commercialization of any unauthorized use or disclosure of information. Furthermore,biologic products is subject to extensive regulation, and we cannot provide assurance thatmay not obtain regulatory approvals for any of our employees, consultants, contract personnel, or collaborators, either accidentally or through willful misconduct, will not cause serious damageproduct candidates.
The clinical development, manufacturing, labeling, packaging, storage, recordkeeping, advertising, promotion, export, import, marketing and distribution and other possible activities relating to our programs and/current lead antibody product candidates, as well as any other antibody product candidate that we may develop in the future, are subject to extensive regulation in the United States and outside the US as biologics.
If we experience delays in obtaining approval, or if we fail to obtain approval of our strategy,product candidates, the commercial prospects for example by disclosing important trade secrets, know‑how or proprietary informationour product candidates may be harmed and our ability to generate revenues will be materially impaired which would adversely affect our competitors. It is also possible thatbusiness, prospects, financial condition and results of operations.
We face significant competition from other biotechnology and pharmaceutical companies and our trade secrets, know‑how oroperating results will suffer if we fail to compete effectively.
The biotechnology and pharmaceutical industries are intensely competitive. We have competitors both in the United States and internationally, including major multinational pharmaceutical companies, biotechnology companies, universities and other proprietary information could be obtained by third partiesresearch institutions. Many of our competitors have substantially greater financial, technical and other resources, such as larger research and development staff and experienced marketing and manufacturing organizations and well-established sales forces. Competition may increase further as a result of breachesadvances in the commercial applicability of technologies and greater availability of capital for investment in these industries. Our competitors may succeed in developing, acquiring or licensing on an exclusive basis, drug products that are more effective or less costly than any product candidate that we are currently developing or that we may develop.
Competition in autoimmune disease and cancer drug development is intense, with hundreds of compounds in clinical trials by large multinational pharmaceutical companies. In addition, many currently marketed drugs are undergoing clinical testing in new indications in order to expand their use to new patient populations. Other companies, including many large international companies, are developing bispecific antibody technologies and checkpoint inhibitors. This includes products in preclinical and clinical development. Some of these agents have received marketing approval, and companies continue to conduct clinical trials to expand their currently approved indications. Alternative technologies, such as standard chemotherapy, cellular therapies and cancer vaccines, may also compete with our physical or electronic security systems. Any disclosureproducts for patients to conduct clinical trials and future potential market share.
46
Our ability to third partiescompete successfully will depend largely on our ability to leverage our experience in drug discovery and development to:
| 1. | discover and develop products that are superior to other products in the market; |
| 2. | attract qualified scientific, product development and commercial personnel; |
| 3. | obtain and maintain patent and/or other proprietary protection for our products and technologies; |
| 4. | obtain required regulatory approvals; and |
| 5. | successfully collaborate with pharmaceutical companies in the discovery, development and commercialization of new products. |
Established biopharmaceutical companies may invest heavily to accelerate discovery and development of products that could allowmake our product candidates less competitive. In addition, any new product that competes with an approved product must demonstrate compelling advantages in efficacy, convenience, tolerability and safety in order to overcome price competition and to be commercially successful. Accordingly, our competitors may succeed in obtaining patent protection, receiving FDA approval or discovering, developing and commercializing medicines before we do, which would have a material adverse impact on our business. We will not be able to learnsuccessfully commercialize our trade secretsproduct candidates without establishing sales and use the information in competition against us. In addition, others may independently discover our trade secretsmarketing capabilities internally or through collaborators.
Our current and proprietary information. Any action to enforce our rights is likely to be time consumingfuture relationships with healthcare professionals, principal investigators, consultants, customers and expensive, and may ultimately be unsuccessful, or may result in a remedy that is not commercially valuable. These risks are accentuated in foreign countries where laws or law enforcement practices may not protect proprietary rights as fully asthird-party payors in the United States or Europe. Any unauthorized disclosure of our trade secrets or proprietary information could harm our competitive position.
Weand elsewhere may be requiredsubject, directly or indirectly, to reduce the scope of our intellectual property due to third‑party intellectual property claims.
Our competitors may have filed,applicable anti-kickback, fraud and may in the future file, patent applications covering technology similar to ours. Any such patent application may have priority over our patent applications,abuse, false claims, physician payment transparency, health information privacy and security and other healthcare laws and regulations, which could further requireexpose us to obtain rights to issued patents covering such technologies. If another party has filed a U.S. patent application on inventions similar to ours that claims priority to an application filed prior to March 16, 2013, we may have to participate in an interference proceeding declared by the PTO to determine priority of invention in the United States. The costs of these proceedings could be substantial,penalties.
Healthcare providers, physicians and it is possible that such efforts would be unsuccessful if, unbeknownst to us, the other party had independently arrived at the same or similar invention prior to our own invention, resulting in a loss of our U.S. patent position with respect to such inventions. In addition, changes enacted on March 15, 2013 to the U.S. patent laws under the America Invents Act resultedthird-party payors in the United States changingand elsewhere will play a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval. Our current and future arrangements with healthcare professionals, principal investigators, consultants, customers and third-party payors may require us to comply with to broadly applicable fraud and abuse and other healthcare laws, including, without limitation, the federal Anti-Kickback Statute and the federal civil False Claims Act, that may constrain the business or financial arrangements and relationships through which we sell, market and distribute any product candidates for which we obtain marketing approval. In addition, we may be subject to physician payment transparency laws and patient privacy and security regulation by the federal government and by the states and foreign jurisdictions in which we conduct our business.
Efforts to ensure that our future business arrangements with third parties will comply with applicable healthcare laws and regulations may involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, including, without limitation, damages, fines, imprisonment, disgorgement, exclusion from participation in government healthcare programs, such as Medicare and Medicaid, additional reporting requirements and/or oversight if we become subject to a “firstcorporate integrity agreement or similar agreement to invent”resolve allegations of non-compliance with these laws, and the curtailment or restructuring of our operations, as well as reputational harm, which could significantly harm our business.
Present and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and affect the prices we may obtain.
Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been
47
significantly affected by major legislative initiatives. Healthcare reform measures, if approved, may result in more rigorous coverage criteria and lower reimbursement, and in additional downward pressure on the price that may be charged for any of our product candidates.
Even if we are able to commercialize any product candidates, our product candidates may be subject to unfavorable pricing regulations, third-party coverage and reimbursement policies or healthcare reform initiatives.
Our ability to commercialize any product candidates successfully will depend, in part, on the extent to which coverage and adequate reimbursement for our product candidates will be available from government payor programs at the federal and state levels, including Medicare and Medicaid, private health insurers, managed care plans and other third-party payors. If coverage and adequate reimbursement are not available or reimbursement is available only to limited levels, we may not be able to successfully commercialize any product candidates for which marketing approval is obtained.
The regulations that govern marketing approvals, pricing, coverage and reimbursement for new drugs and biological products vary widely from country to country. Current and future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. Some countries require approval of the sale price of a “firstproduct 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 file” country.continuing governmental control even after initial approval is granted. As a result, we may lose the abilitymight obtain marketing approval for a product in a particular country, but then be subject to obtain a patent if a third-party files with the PTO first and could become involved in proceedings before the PTO to resolve disputes related to inventorship. We may also become involved in similar proceedings in other jurisdictions.
Furthermore, recent changes in U.S. patent law under the America Invents Act allows for post‑issuance challenges to U.S. patents, including ex parte reexaminations, inter parte reviews and post‑grant oppositions. There is significant uncertainty as to how the new laws will be applied and if our U.S. patents are challenged using such procedures, we may not prevail, possibly resulting in altered or diminished claim scope or loss of patent rights altogether. Similarly, some countries, notably membersprice regulations that delay commercial launch of the European Union, also have post grant opposition proceedingsproduct, possibly for lengthy time periods, and negatively impact the revenues able to be generated from the sale of the product in that can result in changes in scope and/or cancellation of patent claims.
46
Our products could infringe patents and other property rights of others, whichcountry. Adverse pricing limitations may result in costly litigation and, if we are not successful, could cause us to pay substantial damages or limithinder our ability to commercializerecoup our products, which could have a material adverse effect on our business.
Our commercial success depends upon our ability, and the ability of our collaborators, to develop, manufacture, market and sellinvestment in one or more product candidates, even if our product candidates and use our proprietary technologies without infringing the patents and other proprietary rights of third parties. obtain marketing approval.
There is considerable intellectual property litigation in the biotechnology and pharmaceutical industries. For example, we are aware of issued U.S. patents and patent applications owned by Genentech that may relate to and claim components of certain of our product candidates, including XmAb5871, XmAb7195 and XmAb5574/MOR208 or their manufacture. We believe that these patents and patent applications will expire in the United States in 2020 and 2021, respectively. Furthermore, we are aware of a recently issued patent owned by Merus B.V. (Merus) that may relate to and claim components of our bispecific product candidates, including XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb23104, XmAb22814, and XmAb24306, and will putatively expire in 2033. It is possible that these terms could be extended, for example, as a result of patent term restoration to compensate for regulatory delays. While we believe that our current development of these five candidates currently falls into the “safe harbor” of non‑infringement under 35 U.S.C. §271(e)(1), this protection terminates upon commercialization. In addition, there can be no assurance that our interpretation of this statutory exemption would be upheld. Furthermore, while we believe that claims in the Genentech patentsproduct candidates, if they are either invalid or not infringed, we cannot assure you that if we were suedapproved for infringement of these patents that we would prevail. We are currently evaluating the Merus patent; based on our analysis to date we believe there exists reasonable argument of invalidity and/or infringement; however, we cannot assure that this position will not change upon further investigation. In order to successfully challenge the validity of any issued U.S. patent, we would need to overcome a presumption of validity. This burden is a high one requiring us to present clear and convincing evidence as to the invalidity of such claims. There is no assurance that a court would find these claims to be invalid or not infringed.
In addition, as the biopharmaceutical industry expands and more patents are issued, the risk increases that there may be patents issued to third parties that relate to our products and technology of which we are not aware or that we must challenge to continue our operations as currently contemplated. Our products may infringe or may be alleged to infringe these patents. Because some patent applicationssale in the United States mayor in other countries, will be maintained in secrecy until the patents are issued, because patent applications in the United Statesconsidered medically reasonable and many foreign jurisdictions are typicallynecessary for a specific indication, that they will be considered cost-effective by third-party payors, that coverage or an adequate level of reimbursement will be available, or that third-party payors’ reimbursement policies will not published until eighteen months after filing and because publications in the scientific literature often lag behind actual discoveries, we cannot be certain that others have not filed patents that may coveradversely affect our technologies,ability to sell our product candidates or their use. Additionally, pending patent applications which have been published can,profitably if they are approved for sale.
Our business involves the controlled use of hazardous materials and as such we are subject to certain limitations, be later amended in a manner that could cover our technologies, our products or the use of our products. We may become party to, or threatenedenvironmental and occupational safety laws. Continued compliance with future adversarial proceedings or litigation regarding intellectual property rights with respect to our products and technology. Third parties may assert infringement claims against us based on existing patents or patents that may be granted in the future.
If we are sued for patent infringement, we would need to demonstrate that our products or methods either do not infringe the patent claims of the relevant patent or that the patent claims are invalid, and we may not be able to do this. Proving invalidity 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. Even if we are successful in these proceedings, welaws may incur substantial costs and divert management’s timefailure to maintain compliance could result in liability for damages that may exceed our resources.
Our research, manufacturing and attention in pursuing these proceedings, which could have a material adverse effect on us.
Any such claims are likely to be expensive to defend,development processes, and somethose of our competitors maythird-party contractors and partners, involve the controlled use of hazardous materials. We and our manufacturers are subject to federal, state and local laws and regulations governing the use, manufacture, storage, handling and disposal of such materials and certain waste products. Our operations involve the use of hazardous and flammable materials, including chemicals and biological materials. Our operations also produce hazardous waste products. The risk of accidental contamination or injury from these materials cannot be able to sustaincompletely eliminated. In the costsevent of complex patent litigation more effectively than we can because they have substantially greater resources.
47
If we are found to infringe a third party’s intellectual property rights,such an accident, we could be held liable for any damages that result, and any such liability could exceed our resources. We are not insured against this type of liability. We may be required to obtain a license from such third partyincur significant costs to continue developingcomply with environmental laws and marketingregulations in the future, and our products and technology. operations, business or assets may be materially adversely affected by current or future environmental laws or regulations or any liability thereunder.
We may also electbecome subject to enter into suchthe risk of product liability claims.
We face an inherent risk of product liability as a licenseresult of the clinical testing of our product candidates and will face an even greater risk if we or our partners commercialize any products. Human therapeutic products involve the risk of product liability claims and associated adverse publicity. Currently, the principal risks we face relate to patients in order to settle litigationour clinical trials, who may suffer unintended consequences. Claims might be made by patients, healthcare providers or in order to resolve disputes prior to litigation. However,pharmaceutical companies or others. For example, we may not be ablesued if any product we develop allegedly causes injury or is found to obtain any required license on commercially reasonable termsbe otherwise unsuitable during clinical testing, manufacturing, marketing, or at all. Even if we were ablesale. Any such product liability
48
claims may include allegations of defects in manufacturing, defects in design, a failure to obtainwarn of dangers inherent in the product, negligence, strict liability, and a license, it could be non‑exclusive, thereby giving our competitors access to the same technologies licensed to us, and could require us to make substantial royalty payments. Webreach of warranties. Claims could also be forced, including by court order,asserted under state consumer protection acts. If we cannot successfully defend ourselves against product liability claims, we may incur substantial liabilities or be required to cease commercializing the infringing technology or product. In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees if we are found to have willfully infringed a patent. A findinglimit commercialization of infringement could prevent us from commercializing our product candidates, or force us to cease some of our business operations, which could materially harm our business. Claims that we have misappropriated the confidential information or trade secrets of third parties could have a similar negative impact on our business.if approved. Even successful defense would require significant financial and management resources.
General Risk Factors
Our intellectual property may be infringed upon by a third party.
Third parties may infringe one or more of our issued patents or trademarks. We cannot predict if, when or where a third party may infringe one or more of our issued patents or trademarks. To counter infringement, we may be required to file infringement claims, which can be expensive and time consuming. There is no assurance that we would be successful in a court of law in proving that a third party is infringing one or more of our issued patents or trademarks. Any claims we assert against perceived infringers could also provoke these parties to assert counterclaims against us, alleging that we infringe their intellectual property. In addition, in a patent infringement proceeding, a court may decide that a patent of ours is invalid or unenforceable, in whole or in part, construe the patent’s claims narrowly and/or refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question, any of which may adversely affect our business. Even if we are successful in proving in a court of law that a third party is infringing one or more of our issued patents or trademarks there can be no assurance that we would be successful in halting their infringing activities, for example, through a permanent injunction, or that we would be fully or even partially financially compensated for any harm to our business. We may be forced to enter into a license or other agreement with the infringing third party at terms less profitable or otherwise commercially acceptable to us than if the license or agreement were negotiated under conditions between those of a willing licensee and a willing licensor. We may not become aware of a third‑partythird-party infringer within legal timeframes for compensation or at all, thereby possibly losing the ability to be compensated for any harm to our business. Such a third party may be operating in a foreign country where the infringer is difficult to locate and/or the intellectual property laws may be more difficult to enforce. Some third‑partythird-party infringers may be able to sustain the costs of complex infringement litigation more effectively than we can because they have substantially greater resources. Any inability to stop third‑partythird-party infringement could result in loss in market share of some of our products or even lead to a delay, reduction and/or inhibition of the development, manufacture or, sale of certain products by us. There is no assurance that a product produced and sold by a third‑partythird-party infringer would meet our or other regulatory standards or would be safe for use. Such third‑partythird-party infringer products could irreparably harm the reputation of our products thereby resulting in substantial loss in market share and profits.
We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties.
We employ individuals who were previously employed at other biotechnology or pharmaceutical companies. We may be subject to claims that we or our employees, consultants or independent contractors have inadvertently or otherwise used or disclosed confidential information of our employees’ former employers or other third parties. 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 do not prevail, we could be required to pay substantial damages and could lose rights to important intellectual property. Even if we are successful, litigation could result in substantial cost and be a distraction to our management and other employees.
48
Risks Related to Employee Matters and Managing Growth and Other Risks Related to Our Business
We are subject to competition for our skilled personnel and may experience challenges in identifying and retaining key personnel that could impair our ability to conduct and grow our operations effectively.
Our planned growth and future success depends on our ability to retain our executive officers and to attract, retain and motivate qualified personnel. If we are not successful in attracting and retaining highly qualified personnel, we may not be able to successfully implement our business strategy. Although we have not experienced problems attracting and retaining highly qualified personnel in the recent past, our industry has experienced a high rate of turnover of management personnel in recent years. Our ability to compete in the highly competitive biotechnology and pharmaceuticals industries depends upon our ability to attract and retain highly qualified management, scientific and medical personnel. We are highly dependent on our current management team, whose services are critical to the successful implementation of our product candidate development and regulatory strategies. In order to induce valuable employees to continue their employment with us, we have provided stock options that vest over time. The value to employees of stock options that vest over time is significantly affected by movements in our stock price that are beyond our control, and may at any time be insufficient to counteract more lucrative offers from other companies.
Despite our efforts to retain valuable employees, members of our management team may terminate their employment with us at any time, with or without notice. Further, we do not maintain “key person” insurance for any of our executives or other employees. The loss of the services of any of our executive officers and our inability to find suitable replacements could harm our business, financial condition, prospects and ability to achieve the successful development or commercialization of our product candidates. Our success also depends on our ability to continue to attract, retain and motivate highly skilled scientific and medical personnel at all levels.
In 2016 we began to increase the number of our employees and expand the scope of our operations with a goal of advancing multiple clinical candidates into development. The increase in employees, especially in clinical development, places a significant strain on our management, operations and financial resources, and we may have difficulty managing this future potential growth. As we continue to grow our operations and advance our clinical programs into later stages of development, it will require us to recruit and retain employees with additional knowledge and skill sets and no assurance can be provided that we will be able to attract employees with the necessary skill set to assist in our growth. Many of the other biotech and pharmaceutical companies and academic institutions that we compete against for qualified personnel have greater financial and other resources, different risk profiles and a longer history in the industry than we do. We also may employ consultants or part‑time and contract employees. There can be no assurance that these individuals are retainable. While we have been able to attract and retain skilled and experienced personnel and consultants in the past, no assurance can be given that we will be able to do so in the future.
We may become subject to the risk of product liability claims.
We face an inherent risk of product liability as a result of the clinical testing of our product candidates and will face an even greater risk if we or our partners commercialize any products. Human therapeutic products involve the risk of product liability claims and associated adverse publicity. Currently, the principal risks we face relate to patients in our clinical trials, who may suffer unintended consequences. Claims might be made by patients, healthcare providers or pharmaceutical companies or others. For example, we may be sued if any product we develop allegedly causes injury or is found to be otherwise unsuitable during clinical testing, manufacturing, marketing or sale. Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict liability and a breach of warranties. Claims could also be asserted under state consumer protection acts. If we cannot successfully defend ourselves against product liability claims, we may incur substantial liabilities or be required to limit commercialization of our product candidates, if approved. Even successful defense would require significant financial and management resources. Regardless of the merits or eventual outcome, liability claims may result in:
|
|
|
|
49
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
We may not have or be able to obtain or maintain sufficient and affordable insurance coverage to cover product liability claims, and without sufficient coverage any claim brought against us could have a materially adverse effect on our business, financial condition or results of operations. We run clinical trials through investigators that could be negligent through no fault of our own and which could affect patients, cause potential liability claims against us and result in delayed or stopped clinical trials. We are required by contractual obligations to indemnify collaborators, partners, third‑partythird-party contractors, clinical investigators, and institutions. These indemnifications could result in a material impact due to product liability claims against us and/or these groups. We currently carry at least $10.0 million in product liability insurance, which we believe is appropriate for our current clinical trials. Although we maintain such insurance, any claim that may be brought against us could result in a court judgment or settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage. Our insurance policies also have various exclusions, and we may be subject to a product liability claim for which we have no coverage. We will have to pay any amounts awarded by a court or negotiated in a settlement that exceed our coverage limitations or that are not covered by our insurance, and we may not have, or be able to obtain, sufficient capital to pay such amounts. We may also need to expand our insurance coverage as our business grows or if any of our product candidates is commercialized. We may not be able to maintain or increase insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise.
49
Our business could be negatively impacted by cyber security threats and other disruptions, including the theft of our intellectual property, and could compromise our information and expose us to liability, which would cause our business and reputation to suffer.
We are increasingly dependent on information technology systems and infrastructure, including mobile technologies, to operate our business. In the ordinary course of our business, we use our data centers and our networks to store and access confidential and proprietary business information. The information includes, among other things, our intellectual property and proprietary information, the confidential information of our collaborators and licensees and the personally identifiable information of our employees, and the individually identified health information of patients participating in our clinical trials. It is important to our operations and business strategy that this electronic information remains secure and is perceived to be secure. The size and complexity of our information technology systems, and those of our partners and third-party vendors with whom we contract together with the volume of data we retain, make such systems potentially vulnerable to breakdown, malicious intrusion, security breaches and other cyber-security attacks.
Information security risks have significantly increased in recent years in part due to the proliferation of new technologies and the increased sophistication and activities of organized crime, hackers, terrorists and other external parties, including foreign state actors. We face various cyber security threats, including cyber security attacks to our information technology infrastructure and attempts by others to gain access to our proprietary or sensitive information. A security breach or privacy violation that leads to disclosure or modification of or prevents access to personally identifiable information or other protected information could harm our reputation, compel us to comply with federal and/or state breach notification laws and foreign law equivalents, subject us to mandatory corrective action, require us to verify the correctness of database contents and otherwise subject us to liability under laws and regulations that protect personal data, resulting in increased costs or loss of revenue. Similarly, the loss of clinical trial data from completed or ongoing or planned clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. Moreover, a security breach that exposes our confidential intellectual property could compromise our patent portfolio. Additionally, theft of our intellectual property or proprietary business information could require substantial expenditures to remedy. If we are unable to prevent such security breaches or privacy violations or implement satisfactory remedial measures, our operations could be disrupted, and we may suffer loss of reputation, financial loss and other regulatory penalties because of lost or misappropriated information. In addition, these breaches and other inappropriate access can be difficult to detect, and any delay in identifying them may lead to increased harm of the type described above. Moreover, the prevalent use of mobile devices that access confidential information increases the risk of data security breaches, which could lead to the loss of confidential information, trade secrets or other intellectual property. As cyber threats continue to evolve, we may be required to expend significant additional resources to continue to modify or enhance our protective measures or to investigate and remediate any information security vulnerabilities.
The procedures and controls we use to monitor these threats and mitigate our exposure may not be sufficient to prevent cyber security incidents. The result of these incidents could have a material adverse effect on our business, financial condition and results of operations including disrupted operations, lost opportunities, misstated financial data, liability for stolen assets or information, increased costs arising from the implementation of additional security protective measures, litigation and reputational damage. Any remedial costs or other liabilities related to cyber security incidents may not be fully insured or indemnified by other means.
Compliance with global privacy and data security requirements could result in additional costs and liabilities to us or inhibit our ability to collect and process data globally, and the failure to comply with such requirements could have a material adverse effect on our business, financial condition or results of operations.
The regulatory framework for the collection, use, safeguarding, sharing, transfer and other processing of information worldwide is rapidly evolving and is likely to remain uncertain for the foreseeable future. For example, the EU’s General Data Protection Regulation (GDPR), imposes strict obligations on the processing of personal data, including personal health data, and the free movement of such data. The GDPR applies to any company established in the EU as well as any company outside the EU that processes personal data in connection with the offering of goods or services to individuals in the EU or the monitoring of their behavior.
50
As such, the GDPR will apply to us in connection with any clinical trials we conduct in the EU. The GDPR enhances data protection obligations for processors and controllers of personal data, including, for example, obligations relating to: processing health and other sensitive data; obtaining consent of individuals; providing notice to individuals regarding data processing activities; responding to data subject requests; taking certain measures when engaging third-party processors; notifying data subjects and regulators of data breaches; implementing safeguards to protect the security and confidentiality of personal data; and transferring personal data to countries outside the EU, including the U.S. The GDPR imposes substantial fines for breaches of data protection requirements, which can be up to four percent of global revenue or 20 million euros, whichever is greater, and it also confers a private right of action on data subjects for breaches of data protection requirements. The GDPR and other changes in laws or regulations associated with the enhanced protection of certain types of sensitive data, such as healthcare data or other personal information from our clinical trials, could require us to change our business practices or lead to government enforcement actions, private litigation or significant penalties against us and could have a material adverse effect on our business, financial condition or results of operations.
Additionally, California recently enacted legislation that has been dubbed the first “GDPR-like” law in the U.S. Known as the California Consumer Privacy Act (CCPA), it creates new individual privacy rights for consumers (as that word is broadly defined in the law) and places increased privacy and security obligations on entities handling personal data of consumers or households. The CCPA, which went into effect on January 1, 2020, requires covered companies to provide new disclosures to California consumers, and provides such consumers new ways to opt-out of certain sales of personal information. The CCPA provides for civil penalties for violations, as well as a private right of action for data breaches that is expected to increase data breach litigation. The CCPA may increase our compliance costs and potential liability. Some observers have noted that the CCPA could mark the beginning of a trend toward more stringent privacy legislation in the U.S., which could increase our potential liability and adversely affect our business.
We may be vulnerable to disruption, damage and financial obligation as a result of system failures.
Despite the implementation of security measures, any of the internal computer systems belonging to us, our collaborators or our third-party service providers are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failure. Any system failure, accident or security breach that causes interruptions in our own, in collaborators’ or in third-party service vendors’ operations could result in a material disruption of our drug discovery and development programs. For example, the loss of clinical trial data from completed or future clinical trials could result in delays in our or our partners’ regulatory approval efforts and significantly increase our costs in order to recover or reproduce the lost data. To the extent that any disruption or security breach results in a loss or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information, we may incur liability as a result, our drug discovery programs and competitive position may be adversely affected and the further development of our product candidates may be delayed. Furthermore, we may incur additional costs to remedy the damages caused by these disruptions or security breaches.
Our employees may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements and insider trading.
We are exposed to the risk of employee fraud or other misconduct. Misconduct by employees could include intentional failures to comply with FDA regulations, to provide accurate information to the FDA, to comply with manufacturing standards we have established, to comply with federal and state healthcare fraud and abuse laws and regulations, or to report financial information or data accurately or disclose unauthorized activities to us. In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self‑dealingself-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. Employee misconduct could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation. We have adopted a Code of Business Conduct and Ethics, but 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 governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations. If any such actions are instituted against us,
51
and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of significant civil, criminal, and administrative sanctions, and our reputation.
50
In addition, during the course of our operations our directors, executives, and employees may have access to material, nonpublic information regarding our business, our results of operations, or potential transactions we are considering. We may not be able to prevent a director, executive, or employee from trading in our common stock on the basis of, or while having access to, material, nonpublic information. If a director, executive, or employee was to be investigated or an action was to be brought against a director, executive, or employee for insider trading, it could have a negative impact on our reputation and our stock price. Such a claim, with or without merit, could also result in substantial expenditures of time and money, and divert attention of our management team from other tasks important to the success of our business.
We may be vulnerable to disruption, damage and financial obligation as a result of system failures.
Despite the implementation of security measures, any of the internal computer systems belonging to us, our collaborators or our third‑party service providers are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failure. Any system failure, accident or security breach that causes interruptions in our own, in collaborators’ or in third‑party service vendors’ operations could result in a material disruption of our drug discovery and development programs. For example, the loss of clinical trial data from completed or future clinical trials could result in delays in our or our partners’ regulatory approval efforts and significantly increase our costs in order to recover or reproduce the lost data. To the extent that any disruption or security breach results in a loss or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information, we may incur liability as a result, our drug discovery programs and competitive position may be adversely affected and the further development of our product candidates may be delayed. Furthermore, we may incur additional costs to remedy the damages caused by these disruptions or security breaches.
Our business involves the controlled use of hazardous materials and as such we are subject to environmental and occupational safety laws. Continued compliance with these laws may incur substantial costs and failure to maintain compliance could result in liability for damages that may exceed our resources.
Our research, manufacturing and development processes, and those of our third‑party contractors and partners, involve the controlled use of hazardous materials. We and our manufacturers are subject to federal, state and local laws and regulations governing the use, manufacture, storage, handling and disposal of such materials and certain waste products. Our operations involve the use of hazardous and flammable materials, including chemicals and biological materials. Our operations also produce hazardous waste products. The risk of accidental contamination or injury from these materials cannot be completely eliminated. In the event of such an accident, we could be held liable for any damages that result, and any such liability could exceed our resources. We are not insured against this type of liability. We may be required to incur significant costs to comply with environmental laws and regulations in the future, and our operations, business or assets may be materially adversely affected by current or future environmental laws or regulations or any liability thereunder.
Risks Related to Ownership of Our Common Stock
The market price of our common stock is likely to be highly volatile, and you could lose all or part of your investment.
Prior to our initial public offering (IPO), there was no public market for our common stock. The trading price of our common stock is likely to be volatile. Since our IPO, the trading price of our common stock has ranged from a low of approximately $5.75 to a high of approximately $48.38. Our stock price could be subject to wide fluctuations in response to a variety of factors, including the following:
|
|
|
|
|
|
51
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
In addition, the stock market in general, and the NASDAQ Global Market and biotechnology companies in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies. Broad market and industry factors may negatively affect the market price of our common stock, regardless of our actual operating performance.
In the past, securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for us because biopharmaceutical companies have experienced significant stock price volatility in recent years. If we face such litigation, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business.
52
Our principal stockholders, directors and management own a significant percentage of our stock and will be able to exert significant control over matters subject to stockholder approval.
Based on information available to us as of December 31, 2018 our executive officers, directors, 5% stockholders and their affiliates beneficially owned, as a group, approximately 76.97% of our voting stock. Further John S. Stafford III, a former director of the Company, beneficially owns approximately 12.5% of our voting stock and his family members beneficially own approximately an additional 3.8% of our voting stock.
Therefore, our officers, directors and 5% stockholders and their affiliates, including Mr. Stafford, will have the ability to influence us through this ownership position and so long as they continue to beneficially own a significant amount of our outstanding voting stock. These stockholders may be able to determine all matters requiring stockholder approval and this concentration of ownership may deprive other stockholders from realizing the true value of our common stock. For example, these stockholders, acting together, may be able to control elections of directors, amendments of our organizational documents, or approval of any merger, sale of assets, or other major corporate transaction. This may prevent or discourage unsolicited acquisition proposals, offers for our common stock or other transactions or arrangements that you may believe are in your best interest as one of our stockholders.
Raising additional funds through debt or equity financing may be dilutive or restrict our operations and raising funds through licensing may require us to relinquish rights to our technology or product candidates.
To the extent that additional capital is raised through the sale of equity or convertible debt securities, the issuance of those securities could result in substantial dilution for our current stockholders and the terms may include liquidation or other preferences that adversely affect the rights of our current stockholders. Existing stockholders may not agree with our financing plans or the terms of such financings. Moreover, the incurrence of debt financing could result in a substantial portion of our operating cash flow being dedicated to the payment of principal and interest on such indebtedness and could impose restrictions on our operations. Debt financing and preferred 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. In addition, if we raise additional funds through product development partnerships and licensing arrangements, it may be necessary to relinquish potentially valuable rights to our products or proprietary technologies, or grant licenses on terms that are not favorable to us. If we are unable to obtain additional funding on required timelines, we may be required to (1) seek collaborators for one or more of our product candidates at an earlier stage than otherwise would be desirable or on terms that are less favorable than might otherwise be available; (2) relinquish or license on unfavorable terms our rights to technologies or product candidates that we otherwise would seek to develop or commercialize ourselves; or (3) significantly curtail one or more of our research or development programs or cease operations altogether. Additional funding may not be available to us on acceptable terms, or at all.
The clinical development stage of our operations may make it difficult for you to evaluate the success of our business to date and to assess our future viability.
Our operations to date have been limited to organizing and staffing our company, business planning, raising capital, developing our proprietary XmAb technology platform, identifying potential product candidates, and conducting preclinical studies and clinical trials. We have or are currently conducting early phase clinical trials for XmAb5871, XmAb7195, XmAb14045, XmAb13676, XmAb18087, and XmAb20717, but have not completed any late stage clinical trials for these or any other product candidate. We have not yet demonstrated our ability to successfully complete any pivotal clinical trials, obtain regulatory approvals, manufacture a commercial scale product, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful product commercialization. Consequently, any predictions you make about our future success or viability may not be as accurate as they could be if we were further advanced in development of our product candidates.
In addition, we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors. We will need to transition at some point from a company with a research and development focus to a company capable of supporting commercial activities. We may not be successful in such a transition.
53
We expect our financial condition and operating results to continue to fluctuate significantly from quarter to quarter and year to year due to a variety of factors, many of which are beyond our control. Accordingly, you should not rely upon the results of any quarterly or annual periods as indications of future operating performance.
If our internal control over financial reporting is not effective, we may not be able to accurately report our financial results or file our periodic reports in a timely manner, which may cause investors to lose confidence in our reported financial information and may lead to a decline in our stock price.
Effective internal control over financial reporting is necessary for us to provide reliable financial reports in a timely manner. If we fail to adequately staff our accounting and finance function to address the additional demands that will be placed upon us as a public company, including the requirements of the Sarbanes‑Oxley Act of 2002, or fail to maintain adequate internal control over financial reporting, it could prevent our management from concluding our internal control over financial reporting is effective and impair our ability to prevent material misstatements in our financial statements, which could cause our business to suffer.
As a large accelerated filer, we are subject to additional internal control requirements of the Sarbanes-Oxley Act of 2002.
Sales of a substantial number of shares of our common stock by our existing stockholders in the public market could cause our stock price to fall.
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. In addition a substantial number of shares of common stock are subject to outstanding options that are or will become 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.
Future sales and issuances of our common stock or rights to purchase common stock, including pursuant to our equity incentive plans, could result in additional dilution of the percentage ownership of our stockholders and could cause our stock price to fall.
We expect that significant additional capital will be needed in the future to continue our planned operations. To the extent we raise additional capital by issuing equity securities, our stockholders may experience substantial dilution. We may sell common stock, convertible securities or other equity securities in one or more transactions at prices and in a manner, we determine from time to time. If we sell common stock, convertible securities or other equity securities in more than one transaction, investors may be materially diluted by subsequent sales. These sales may also result in material dilution to our existing stockholders, and new investors could gain rights superior to our existing stockholders.
Pursuant to our 2013 equity incentive plan (2013 plan), subject to board approval, our management is authorized to grant stock options and other equity‑based awards to our employees, directors and consultants. The number of shares available for future grant under the 2013 plan will automatically increase each year by 4% of all shares of our capital stock outstanding as of December 31 of the prior calendar year, subject to the ability of our Board of Directors to take action to reduce the size of the increase in any given year. As of December 31, 2018, we had options to purchase 5,966,928 shares outstanding under our equity compensation plans. In addition, we are also authorized to grant equity awards, including stock options, to our employees, directors and consultants, covering up to 9,581,833 shares of our common stock, pursuant to our equity compensation plans. We plan to register the number of shares available for issuance or subject to outstanding awards under our equity compensation plans. If our Board of Directors elects to increase the number of shares available for future grant by the maximum amount each year, our stockholders may experience additional dilution, which could cause our stock price to fall.
54
U.S. federal income tax reform could adversely affect us.
In December 2017, U.S. federal tax legislation, commonly referred to as the Tax Cuts and Jobs Act (TCJA), was signed into law, significantly reforming the Internal Revenue Code of 1986, as amended (IRC). The TCJA, among other things, includes changes to U.S. federal tax rates, imposes significant additional limitations on the deductibility of interest, limits the deduction for net operating losses to 80% of current year taxable income, eliminates net operating loss carrybacks, allows for the expensing of capital expenditures, puts into effect the migration from a “worldwide” system of taxation to a territorial system and modifies or repeals many business deductions and credits. The overall impact of this tax reform is uncertain, and our business and financial condition could be adversely affected.
New legislation or regulation which could affect our tax burden could be enacted by any governmental authority. We cannot predict the timing or extent of such tax-related developments which could have a negative impact on our financial results. Additionally, we use our best judgment in attempting to quantify and reserve for these tax obligations. However, a challenge by a taxing authority, our ability to utilize tax benefits such as carryforwards or tax credits, or a deviation from other tax-related assumptions may cause actual financial results to deviate from previous estimates.
Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited.
Our net operating loss (NOL) carryforwards generated in tax years ending on or prior to December 31, 2017, are only permitted to be carried forward for 20 years under applicable U.S. tax law. Under the TCJA, our federal NOLs generated in tax years ending after December 31, 2017, may be carried forward indefinitely, but the deductibility of such federal NOLs generated in tax years beginning after December 31, 2017, is limited. It is uncertain if and to what extent various states will conform to the TCJA. In addition, under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, and corresponding provisions of state law, if a corporation undergoes an “ownership change,” which is generally defined as a greater than 50% change, by value, in its equity ownership over a three-year period, the corporation’s ability to use its pre-change NOL carryforwards and other pre-change U.S. tax attributes (such as research tax credits) to offset its post-change income or taxes may be limited. Upon analysis, we believe that we triggered an “ownership change” as a result of the sale of stock in connection with our IPO in December 2013 and our net operating loss and tax credit carryforwards have been limited as a result. It is also possible that we have in the past undergone, and in the future may undergo, additional ownership changes besides our IPO that could result in additional limitations on our net operating loss and tax credit carryforwards.
As a result, our pre-2018 NOL carryforwards may expire prior to being used, and our NOL carryforwards generated in 2018 and thereafter will be subject to a percentage limitation. Similar provisions of state tax law may also apply to limit our use of accumulated state tax attributes. In addition, at the state level, there may be periods during which the use of NOLs is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed. As a result, if we earn net taxable income, we may be unable to use all or a material portion of our NOLs and other tax attributes, which could potentially result in increased future tax liability to us and adversely affect our future cash flows.
We do not intend to pay dividends on our common stock so any returns will be limited to the value of our stock.
We have never declared or paid any cash dividend on our common stock. We currently anticipate that we will retain future earnings for the development, operation and expansion of our business and do not anticipate declaring or paying any cash dividends for the foreseeable future. Any return to stockholders will therefore be limited to the appreciation of their stock.
Provisions in our amended and restated certificate of incorporation and bylaws, as well as provisions of Delaware law, could make it more difficult for a third party to acquire us or increase the cost of acquiring us, even if doing so would benefit our stockholders or remove our current management.
Some provisions of our charter documents and Delaware law may have anti‑takeover effects that could discourage an acquisition of us by others, even if an acquisition would be beneficial to our stockholders and may prevent attempts by our stockholders to replace or remove our current management. These provisions include:
55
|
|
|
|
|
|
|
|
These provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our Board of Directors, which is responsible for appointing the members of our management. In addition, we are subject to Section 203 of the Delaware General Corporation Law, which generally prohibits a Delaware corporation from engaging in any of a broad range of business combinations with an interested stockholder for a period of three years following the date on which the stockholder became an interested stockholder, unless such transactions are approved by our Board of Directors. This provision could have the effect of delaying or preventing a change of control, whether or not it is desired by or beneficial to our stockholders. Further, other provisions of Delaware law may also discourage, delay or prevent someone from acquiring us or merging with us. Any provision of our certificate of incorporation or bylaws or Delaware law that has the effect of delaying or deterring change in control could limit the opportunity for our stockholders to receive a premium for their shares of our common stock, and could also affect the price that some investors are willing to pay for our common stock.
Requirements associated with being a public reporting company will continue to increase our costs significantly, as well as divert significant company resources and management attention.
We have been subject to the reporting requirements of the Exchange Act and the other rules and regulations of the Securities and Exchange Commission (SEC) since December 2013. Effective for the year-ended December 31, 2016, we became a large accelerated filer and are subject to additional internal control and SEC reporting obligations. Compliance with the various reporting and other requirements applicable to public reporting companies requires considerable time, attention of management, and financial resources.
Further, the listing requirements of The NASDAQ Global Market require that we satisfy certain corporate governance requirements relating to director independence, distributing annual and interim reports, stockholder meetings, approvals and voting, soliciting proxies, conflicts of interest and a code of conduct. Our management and other personnel need to devote a substantial amount of time to ensure that we comply with all of these requirements. Moreover, the reporting requirements, rules and regulations increase our legal and financial compliance costs and also make some activities more time‑consuming and costly. These reporting requirements, rules and regulations, coupled with the increase in potential litigation exposure associated with being a public company, could also make it more difficult for us to attract and retain qualified persons to serve on our board of directors or board committees or to serve as executive officers, or to obtain certain types of insurance, including directors’ and officers’ insurance, on acceptable terms.
In addition, being a public company could make it more difficult or more costly for us to obtain certain types of insurance, including directors’ and officers’ liability insurance, and we may be forced to accept reduced policy limits and coverage or incur substantially higher costs to obtain the same or similar coverage. The impact of these events could also make it more difficult for us to attract and retain qualified persons to serve on our board of directors, our board committees or as executive officers.
Any changes we make to comply with these obligations may not be sufficient to allow us to satisfy our obligations as a public company on a timely basis, or at all.
56
None.
Our principal laboratory and administrative facilities are located in Monrovia, California, which is located in the greater Los Angeles region. We currently lease 48,000 square feet of laboratory and office space in Monrovia, California. The original lease was for 24,000 square feet under a lease that expireswas set to expire in June 2020. In July 2017,April and September 2020, we entered into amendments to the lease that extended the term under the original terms through October 2020. In November 2020, we entered into an amendedamendment to the lease which extends the lease to December 2025.
In July 2017, under a separate lease agreement, we entered into a lease for an additional 24,000 square feet of space in the same building. The amended lease is forincludes a 64-month term for the additional 24,000 square feet with an option to renew for an additional five years at then market rates. The lease terms for the original space were not amended. We also lease approximately 5,700 square feet of office space in San Diego, California. In June 2017, we entered into a new lease for 23,500 of additionaloffice space in San Diego. The new lease term has a 61-month term beginning from August 2017 and includes an option to renew for an additional five years. We believe that our existing facilities are adequate to meet our current needs and that suitable additional alternative spaces will be available to meet future needs on commercially reasonable terms.
None.
Not applicable.
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
Market Information
Our common stock began trading on The NASDAQNasdaq Global Market on December 3, 2013 under the symbol “XNCR.” Prior to such time, there was no public market for our common stock. On February 15, 2019,16, 2021, the closing price for our common stock as reported on the NASDAQNasdaq Global Market was $36.46. $50.09.
52
Holders of Record
As of February 15, 2019,16, 2021, we had 56,292,16957,945,225 shares of common stock outstanding held by approximately 200185 stockholders of record. The actual number of stockholders is greater than this number of record holders and includes stockholders who are beneficial owners, but whose shares are held in street name by brokers and other nominees. This number of holders of record also does not include stockholders whose shares may be held in trust by other entities.
Dividend Policy
We have never declared or paid any cash dividends on our common stock. We currently intend to retain all available funds and any future earnings to support our operations and finance the growth and development of our business. We do not intend to pay cash dividends on our common stock for the foreseeable future. Any future determination related to our dividend policy will be made at the discretion of our boardBoard of directorsDirectors and will depend upon, among other factors, our results of operations, financial condition, capital requirements, contractual restrictions, business prospects and other factors our boardBoard of directorsDirectors may deem relevant.
57
Securities Authorized for Issuance Under Equity Compensation Plans
Information about our equity compensation plans is incorporated herein by reference to Item 12 of Part III of this Annual Report.
Performance Graph
The following graph shows a comparison from December 31, 20132015 through December 31, 20182020 of the cumulative total return for our common stock, the NASDAQNasdaq Biotechnology Index (NBI) and the NASDAQNasdaq Composite Index (CCMP). The graph assumes an initial investment of $100 on December 31, 20132015 and assumes reinvestment of the full amount of all dividends, if any. The comparisons in the graph are not intended to forecast or be indicative of possible future performance of our common stock.
The performance graph shall not be deemed to be incorporated by reference by means of any general statement incorporating by reference this Form 10‑K10-K into any filing under the Securities Act of 1933, as amended or the Exchange Act, except to the extent that we specifically incorporate such information by reference, and shall not otherwise be deemed filed under such acts.
Recent Sales of Unregistered Securities
There were no sales of unregistered securities during the year ended December 31, 2018.2020.
53
Purchases of Equity Securities by the Issuer and Affiliated Purchasers
None.
58
The selected financial data set forth below as of December 31, 20182020, and 2017,2019, and for the years ended December 31, 2018, 2017,2020, 2019, and 2016,2018, are derived from our audited financial statements included elsewhere in this report.Annual Report. This information should be read in conjunction with those financial statements and notes thereto and with “Management’s Discussion and Analysis of Financial Condition and Results of Operations.” The selected financial data set forth below as of December 31, 20162017 and 20152016 are derived from our audited financial statements that are contained in reports previously filed with the SEC, not included herein. Periods prior to 2018 have been revised to reflect the adoption of Accounting Standards Codification Topic 606 (ASC 606) related to changes in standards for revenue recognition. Revised financial data under ASC 606 as of and for the year ended December 31, 2014 have not been subjected to audit. Amounts(Amounts are in thousands, except share and per share amounts.amounts).
| | | | | | | | | | | | | | | |
| | Year Ended | |||||||||||||
| | December 31, | |||||||||||||
| | 2020 | | 2019 | | 2018 | | 2017 |
| 2016 | |||||
Statement of Operations: |
|
| |
| |
|
| |
|
| |
| | |
|
Revenues |
| $ | 122,694 | | $ | 156,700 | | $ | 40,603 | | $ | 46,150 | | $ | 109,020 |
Operating expenses: | | | | | | | | | | | | | | | |
Research and development | | | 169,802 | | | 118,590 | | | 97,501 | |
| 71,772 | |
| 51,872 |
General and administrative | | | 29,689 | | | 24,286 | | | 22,472 | |
| 17,501 | |
| 13,108 |
Total operating expenses | | | 199,491 | | | 142,876 | | | 119,973 | |
| 89,273 | |
| 64,980 |
Income (loss) from operations | |
| (76,797) | |
| 13,824 | |
| (79,370) | |
| (43,123) | |
| 44,040 |
Other income (expenses) | | | | | | | | | | | | | | | |
Interest income, net | | | 7,264 | | | 13,619 | | | 9,086 | |
| 4,181 | |
| 2,070 |
Other income (expense) | | | 200 | | | (256) | | | (125) | |
| (7) | |
| 6 |
Total other income, net | |
| 7,464 | |
| 13,363 | |
| 8,961 | |
| 4,174 | |
| 2,076 |
Net income (loss) before tax | |
| (69,333) | |
| 27,187 | |
| (70,409) | |
| (38,949) | |
| 46,116 |
Income tax expense (benefit) | | | — | | | 312 | | | — | | | (463) | | | 991 |
Net income (loss) attributable to common stockholders |
| $ | (69,333) | | $ | 26,875 | | $ | (70,409) | | $ | (38,486) | | $ | 45,125 |
Other comprehensive income (loss) | | | | | | | | | | | | | | | |
Net unrealized gain (loss) on marketable securities | | | (1,087) | | | 2,132 | | | 837 | | | (367) | | | (925) |
Comprehensive income (loss) | | $ | (70,420) | | $ | 29,007 | | $ | (69,572) | | $ | (38,853) | | $ | 44,200 |
| | | | | | | | | | | | | | | |
Net income (loss) per share attributed to common stockholders (1): | | | | | | | | | | | | | | | |
Basic |
| $ | (1.21) | | $ | 0.48 | | $ | (1.31) | | $ | (0.82) | | $ | 1.09 |
Diluted | | $ | (1.21) | | $ | 0.46 | | $ | (1.31) | | $ | (0.82) | | $ | 1.07 |
Weighted average shares of common stock used in computed net income (loss) attributable to common stockholders: | | | | | | | | | | | | | | | |
Basic | | | 57,212,737 | | | 56,531,439 | | | 53,942,116 | |
| 46,817,756 | |
| 41,267,329 |
Diluted | | | 57,212,737 | | | 58,467,880 | | | 53,942,116 | |
| 46,817,756 | |
| 42,388,867 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Year Ended | |||||||||||||
|
| December 31, | |||||||||||||
|
| 2018 |
| 2017 |
| 2016 |
| 2015 |
| 2014 | |||||
|
|
|
| (As Revised) |
| (As Revised) |
| (As Revised) |
| (As Revised) | |||||
Statement of Operations Data: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Revenues |
| $ | 40,603 |
| $ | 46,150 |
| $ | 109,020 |
| $ | 26,602 |
| $ | 7,700 |
Operating expenses: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and development |
|
| 97,501 |
|
| 71,772 |
|
| 51,872 |
|
| 34,140 |
|
| 18,516 |
General and administrative |
|
| 22,472 |
|
| 17,501 |
|
| 13,108 |
|
| 11,960 |
|
| 7,461 |
Total operating expenses |
|
| 119,973 |
|
| 89,273 |
|
| 64,980 |
|
| 46,100 |
|
| 25,977 |
Income (loss) from operations |
|
| (79,370) |
|
| (43,123) |
|
| 44,040 |
|
| (19,498) |
|
| (18,277) |
Other income (expenses) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Interest income |
|
| 9,102 |
|
| 4,194 |
|
| 2,091 |
|
| 1,840 |
|
| 33 |
Interest expense |
|
| (16) |
|
| (13) |
|
| (21) |
|
| (13) |
|
| (9) |
Other income (expense) |
|
| (125) |
|
| (7) |
|
| 6 |
|
| (1,081) |
|
| 11 |
Total other income, net |
|
| 8,961 |
|
| 4,174 |
|
| 2,076 |
|
| 746 |
|
| 35 |
Net income (loss) before income tax |
|
| (70,409) |
|
| (38,949) |
|
| 46,116 |
|
| (18,752) |
|
| (18,242) |
Income tax expense (benefit) |
|
| — |
|
| (463) |
|
| 991 |
|
| — |
|
| — |
Net income (loss) attributable to common stockholders |
| $ | (70,409) |
| $ | (38,486) |
| $ | 45,125 |
| $ | (18,752) |
| $ | (18,242) |
Other comprehensive income (loss) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net unrealized gain (loss) on marketable securities available-for-sale, net of tax |
|
| 837 |
|
| (367) |
|
| (925) |
|
| (516) |
|
| — |
Comprehensive income (loss) |
| $ | (69,572) |
| $ | (38,853) |
| $ | 44,200 |
| $ | (19,268) |
| $ | (18,242) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net income (loss) per share attributable to common stockholders (1): |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Basic |
| $ | (1.31) |
| $ | (0.82) |
| $ | 1.09 |
| $ | (0.48) |
| $ | (0.58) |
Diluted |
| $ | (1.31) |
| $ | (0.82) |
| $ | 1.07 |
| $ | (0.48) |
| $ | (0.58) |
Weighted average shares of common stock used in computing net income (loss) per share attributable to common stockholders: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Basic |
|
| 53,942,116 |
|
| 46,817,756 |
|
| 41,267,329 |
|
| 39,015,131 |
|
| 31,390,631 |
Diluted |
|
| 53,942,116 |
|
| 46,817,756 |
|
| 42,388,867 |
|
| 39,015,131 |
|
| 31,390,631 |
(1) | See Note 1 to our Annual Financial Statements appearing elsewhere in this document for a description of the method used to calculate basic and diluted income (loss) per common share. |
5954
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| |||||||||||||||
|
| As of December 31, | ||||||||||||||||||||||||||||
|
| (in thousands) | ||||||||||||||||||||||||||||
|
| 2018 |
| 2017 |
| 2016 |
| 2015 |
| 2014 | ||||||||||||||||||||
|
|
|
|
| (As Revised) |
| (As Revised) |
| (As Revised) |
| (As Revised) | |||||||||||||||||||
| | | | | | | | | | | | | | | | |||||||||||||||
| | As of December 31, | ||||||||||||||||||||||||||||
| | (in thousands) | ||||||||||||||||||||||||||||
| | 2020 |
| 2019 |
| 2018 | | 2017 |
| 2016 | ||||||||||||||||||||
Balance Sheet Data: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| | |
| | |
| | |
| | | |
Cash, cash equivalents and marketable securities |
| $ | 530,469 |
| $ | 363,328 |
| $ | 403,476 |
| $ | 193,321 |
| $ | 54,649 |
| $ | 604,033 | | $ | 601,308 | | $ | 530,469 | | $ | 363,328 | | $ | 403,476 |
Working capital |
|
| 261,874 |
|
| 158,229 |
|
| 50,720 |
|
| 54,883 |
|
| 52,205 | | | 516,611 | |
| 491,847 | |
| 261,874 | |
| 158,229 | |
| 50,720 |
Patents, licenses, and other intangible assets, net |
|
| 11,969 |
|
| 11,148 |
|
| 10,362 |
|
| 9,971 |
|
| 9,116 | | | 15,977 | |
| 14,421 | |
| 11,969 | |
| 11,148 | |
| 10,362 |
Total assets |
|
| 576,732 |
|
| 390,202 |
|
| 429,263 |
|
| 208,210 |
|
| 69,723 | | | 703,244 | |
| 670,250 | |
| 576,732 | |
| 390,202 | |
| 429,263 |
Deferred revenue |
|
| 40,079 |
|
| 60,118 |
|
| 80,168 |
|
| 32,650 |
|
| 2,852 | | | 92,615 | |
| 47,131 | |
| 40,079 | |
| 60,118 | |
| 80,168 |
Total stockholders’ equity |
| $ | 521,681 |
| $ | 316,464 |
| $ | 337,933 |
| $ | 164,911 |
| $ | 62,929 |
| $ | 572,444 | | $ | 593,201 | | $ | 521,681 | | $ | 316,464 | | $ | 337,933 |
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations.
You should read the following discussion and analysis together with “Item 6. Selected Financial Data” and our financial statements and related notes included elsewhere in this Annual Report. The following discussion contains forward‑lookingforward-looking statements that involve risks and uncertainties. Our actual results could differ materially from those expressed or implied in any forward‑lookingforward-looking statements as a result of various factors, including those set forth under the caption “Item 1A. Risk Factors.”
Overview
We are a clinical‑stageclinical-stage biopharmaceutical company focused on discovering and developing engineered monoclonal antibody and other proteincytokine therapeutics to treat severepatients with cancer and life‑threateningautoimmune diseases withwho have unmet medical needs. We are developingadvancing a suitebroad portfolio of clinical-stage drug candidates from our proprietary XmAb® technology platforms that are designedplatforms. We use our protein engineering capabilities to treat cancer, autoimmuneincrease our understanding of protein structure and allergic diseases,interactions and other conditions.to design new XmAb technologies and development candidates with improved properties. In contrast to conventional approaches to antibody design, which focus on the portionsegment of antibodies that interact with target antigens, our protein engineering efforts and the XmAb technologies are focused on the portionFc domain, the part of thean antibody that interacts with multiple segments of the immune system and controls antibody structure. This portion, referred to as theThe Fc domain is constant and interchangeable among antibodies. Ourantibodies, and our engineered Fc domains, the XmAb technology, can be readily substituted for natural Fc domains.
We believeOur protein engineering capabilities and XmAb technologies enable us and our Fc domainspartners to develop antibodies and biotherapeutic drug candidates with improved properties and function, which can provide innovative approaches to treating disease and potential clinical advantage over other treatment options. For example, our capabilities have enabled us to develop an antibody scaffold to rapidly create novel bispecific antibodies that bind two different targets simultaneously, creating entirely new biological mechanisms. Other applications of our XmAb technologies enhance antibody performance by for example, increasing immune inhibitory activity, improving cytotoxicity, extending circulating half‑life, orhalf-life and stabilizing novel protein structures, such as engineered cytokines. Currently, there are two marketed drugs that have been developed with our XmAb technologies.
Refer to Part I, Item 1, "XmAb Bispecific Technologies" and "Other XmAb Fc Technologies" in the description of our business included in this Annual Report on Form 10-K for a discussion of our core Fc technology platforms.
COVID-19
We are closely monitoring the COVID-19 pandemic and continue to evaluate its impact on all aspects of our business, including how it will affect our partners, collaborations, supply chains and research and development operations. While the pandemic did not significantly disrupt our business during the year ended December 31, 2020, the evolving nature of the pandemic prevents us from reasonably predicting how the pandemic will affect our financial condition, results of operations and cash flows due to numerous uncertainties. These uncertainties include the scope, severity and duration of the pandemic, the actions taken to contain the pandemic or mitigate its impacts and the direct
55
and indirect economic effects of the pandemic and containment measures, among others. Many states, including California, where we are headquartered and where our principal place of business is located, and cities therein have instituted quarantines, restrictions, rules and guidelines that affect the continued operation of businesses. Other countries and states where we conduct manufacturing of our drug product, testing activities and clinical sites where patients are enrolled in our clinical trials have enacted similar restrictions that could affect our ability to conduct our drug candidate development and clinical operations.
The potential impacts on our business, revenue, clinical studies and research and development activities of the COVID-19 pandemic include:
| ● | Business: Our broad protein engineering capabilities and technologies are uniquely suited to provide us with opportunities to identify and enhance compounds that may target the novel coronavirus and potentially treat patients with COVID-19. Our partner Vir Biotechnology, Inc. is evaluating VIR-7831, an antibody that targets the SARS-CoV-2 virus in a Phase 3 study. VIR-7831 incorporates our Xtend Fc technology for longer duration of action. VIR-7832, which also targets the SARS-CoV-2 virus, also incorporates Xtend technology and is in the preclinical stages of development. |
| ● | Revenue: We receive upfront payments, milestone payments and royalties from licensing our XmAb technologies and drug candidates. The COVID-19 pandemic has not adversely affected our ability to generate revenues for the year ended December 31, 2020. During the year, we received $165 million from our partnerships and collaborations including those with MorphoSys, Alexion, Gilead, Janssen, Aimmune and Omeros. |
Our ability to earn revenue from these and other partnerships is dependent on the ability of our partners to generate sales from products, such Ultomiris® and Monjuvi®, the ability of our partners to advance their programs through regulatory approval, and the ability of our partners to advance our partnered programs into later stages of development, which provide us with potential milestone payments. If the pandemic continues for an extended period and adversely affects the sales or clinical, development and regulatory progress of partnered programs, the amount of revenue we could earn would be adversely affected.
| ● | Clinical studies: We are currently enrolling patients in six clinical programs, and our partner Genentech is enrolling patients in the Phase 1 study of our co-development program XmAb306 (also known as RG6323). Many partners are also enrolling patients in clinical trials with drug candidates that incorporate one or more of our XmAb technologies. Although the COVID-19 pandemic has not materially affected the development of our clinical programs for the year ended December 31, 2020, some of our clinical programs temporarily experienced slower patient enrollment, and the initiations of new studies for certain programs have been delayed as a result of the COVID-19 pandemic. These delays have not broadly affected the status of our portfolio programs and have been limited to specific trials and specific sites. Many clinical sites have delayed starting new clinical trials and others have postponed enrollment to address the pandemic. |
| ● | Research and development activities: We require all non-laboratory employees to work remotely, and we have implemented additional health, safety and environmental procedures for all onsite laboratory research employees. We believe we provide a safe and healthy environment for our onsite employees who have been able to continue research operations, following an initial period of reduced onsite activities while new policies and procedures were developed and implemented. As of December 31, 2020, these activities have continued without interruption from the pandemic. |
Our development activities include initiating a Phase 1 study of XmAb564 in healthy volunteers and conducting IND-enabling studies for XmAb819. Several other bispecific antibody and other protein structures, while maintaining 99.5% identitycytokine programs are in structure and sequence to natural antibodies. The most recent expansionearlier stages of development. During the third quarter of 2020, the manufacturers of our platformdrug supplies notified us of critical shortages of materials used in their manufacturing processes due to pandemic-related reallocation of resources. The shortages will not affect our current clinical programs as we have sufficient drug supply to continue the ongoing trials without interruption. However, the shortages
56
have extended the development timelines of early-stage development candidates, including XmAb819, by three to six months based on current information from our vendors. The development timelines for additional early-stage programs and ongoing clinical programs could be affected if the supply interruption extends longer than current estimates.
Advancements in our Clinical Portfolio of XmAb Bispecific Antibodies and Cytokine Candidates
Our modular XmAb bispecific technology and protein engineering capabilities enable us to rapidly advance multiple drug candidates into clinical development. We and our partners are currently enrolling Phase 1 studies for seven wholly owned or co-development candidates to treat patients with many different types of cancer, and an eighth, to be developed for patients with autoimmune disease, is expected to enter clinical development in early 2021.
Plamotamab (CD20 x CD3): At the ASH Annual Meeting in December 2019, we presented preliminary safety and anti-tumor activity from the Phase 1 dose-escalation study of plamotamab in B-cell malignancies, including from patients with relapsed or refractory NHL. The early results indicated that plamotamab was generally well tolerated and demonstrated encouraging clinical activity as a monotherapy. We are currently enrolling patients in the ongoing monotherapy dose-escalation study and plan to initiate additional studies in 2021.
In November 2020, we entered a strategic clinical collaboration with MorphoSys AG to investigate the chemotherapy-free triple combination of plamotamab, tafasitamab and lenalidomide in patients with relapsed or refractory DLBCL, first-line DLBCL and relapsed or refractory FL. Plamotamab, which redirects T cells to tumors, and tafasitamab, a CD19-directed XmAb antibody, combine powerful and distinct immune pathways, and this collaboration is designed to generate new clinical insights and accelerate development timelines for the program. MorphoSys and Incyte will provide tafasitamab for the studies, which we will sponsor and fund. Tafasitamab is co-commercialized in the U.S. by MorphoSys and Incyte and is marketed as Monjuvi. Monjuvi, the second product with XmAb technology to be approved for commercial marketing, was approved by the U.S. FDA in July 2020.
XmAb717 (PD-1 x CTLA-4): In November 2020, we presented updated data from the Phase 1 study of XmAb717 in patients with multiple types of advanced solid tumors at the Annual Meeting of SITC. Five cohorts in the expansion portion of the study enrolled patients with melanoma, RCC, NSCLC, CRPC and other cancers without approved checkpoint therapies. XmAb717 was generally well-tolerated, and the most common treatment-related adverse events were irAEs; however, rates of irAEs, including colitis, were lower than typically observed with CTLA-4 blockade. The efficacy analysis included evaluable patients at the recommended dose level, 10.0 mg/kg. A complete response was observed in a patient with melanoma, and partial responses were observed in multiple tumor types, including melanoma, RCC, NSCLC, CRPC and ovarian cancer. The objective response rate across cohorts was 19%. Across the expansion cohorts, approximately half of evaluable patients had at least 10% tumor shrinkage from baseline assessments, and nearly all these reductions occurred in patients with prior checkpoint inhibitor treatment. The median duration of response was 119 days at the time of the data cut off, and 24 patients remained on treatment as of September 30, 2020.
Of nine patients with prostate cancer who had baseline and follow-up PSA assessments, one achieved a PSA reduction of greater than 50 percent. Two additional patients achieved reductions of greater than 30 percent, one of whom had an unconfirmed partial response by RECIST. Six of these nine patients remained on therapy as of the cut-off date. In the first half of 2021, we plan to initiate a Phase 1b study of XmAb717 for patients with certain molecular subtypes of CRPC, as a monotherapy or in combination depending on the subtype, as these patients represent a high unmet medical need.
Vibecotamab (CD123 x CD3): In December 2020, we presented updated data from the Phase 1 study of vibecotamab in patients with relapsed or refractory AML at the ASH Annual Meeting. While CRS was the most common adverse event, the majority was observed in the first dose and was generally manageable with premedication. The efficacy analysis included evaluable patients who received a dose of at least 0.75 mcg/kg, completed at least the first cycle of treatment and had at least one post-treatment disease assessment. Two patients achieved CR, and three patients achieved a CR with incomplete hematologic recovery. Additionally, two patients reached a morphologic leukemia-free state, and one patient experienced partial remission, as assessed by the investigator. The ORR was 15%. Responses
57
appeared to be associated with lower baseline disease burden, indicated by patients with lower blast percentages and lower PD1 expression on CD8+ and CD4+ T cells. Seven responders had a baseline blast count less than or equal to 25% blasts in bone marrow. The ORR increased to 26% when using this threshold to define the population with low disease burden for the analyses. We are continuing the dose escalation study and are reviewing data with our partner, Novartis, in planning additional studies of vibecotamab.
Tidutamab (SSTR2 x CD3): In October 2020, we presented initial dose-escalation data from the ongoing Phase 1 study in patients with NET. Tidutamab was generally well tolerated at the recommended dose identified for the expansion portion of the study. Peripheral blood biomarkers indicated tidutamab induced acute and sustained T-cell activation at this dose, and a dose-dependent increase in proliferation and activation markers of CD8+ T cells was observed, which is consistent with tidutamab’s mechanism of action. The best overall response was stable disease in the analysis to describe clinical activity, and the median duration of treatment was approximately seven months. Completion of enrollment and longer follow-up are required to evaluate progression-free survival and the clinical utility of tidutamab for patients with NETs, which are an indolent, slow-growing tumor type. Considering the biomarker analysis from this study and tidutamab’s encouraging safety profile, we plan to initiate an additional clinical study for patients with Merkel cell carcinoma and small cell lung cancer, SSTR2-expressing tumor types known to be responsive to immunotherapy, in early 2021.
XmAb306/RO7310729 (IL15/IL15Rα-Fc Cytokine):In March 2020, Genentech dosed the first patient in a Phase 1 dose-escalation study evaluating XmAb306, our first cytokine candidate, as a single agent and in combination with atezolizumab for patients with advanced solid tumors. XmAb306 is an IL15/IL15Rα-Fc fusion protein that incorporates our Xtend extended half-life technology, and we are co-developing this program, as well as other potential IL-15 programs, in collaboration with Genentech. We retain the right to perform clinical studies with XmAb306, as well as with other collaboration programs developed in combination with other therapeutic agents, subject to certain restrictions and at our sole expense. Genentech has dosed cohorts of the Phase 1 study of XmAb306 in combination with atezolizumab and at least one additional combination study is currently being planned.
XmAb564 (IL2-Fc Cytokine): XmAb564 is a wholly owned IL2-Fc fusion that we intend to develop for the treatment of patients with autoimmune diseases. In January 2021, the IND application for XmAb564 was allowed by the FDA, and we plan to initiate a Phase 1 study in healthy volunteers in early 2021.
XmAb698 (CD38 x CD3): In 2015, Amgen licensed rights to our preclinical CD38 x CD3 bispecific antibody program and developed AMG 424, which they evaluated in a Phase 1 study. Amgen terminated the program in the second quarter of 2020, indicating it was stopped for adverse events that were likely CD38 target related. Under the terms of the agreement, the rights to the CD38 program, including AMG 424, reverted to us. A new study is currently being planned to start later this year, for the program, which we have renamed XmAb698.
Additional wholly owned XmAb bispecific antibody programs in Phase 1 clinical studies include XmAb841 (CTLA-4 x LAG-3) and XmAb104 (PD-1 x ICOS). We continue enrolling patients with advanced solid tumors to these studies.
Advancements Expanding XmAb Bispecific Platforms
We conduct further research into the function and application of antibody Fc domains in order to expand the scope of our XmAb technology platforms and identify additional XmAb drug candidates. We use the modularity of our XmAb bispecific Fc domains, which enable the rapid design and simplified development oftechnology to build bispecific antibodies and other protein structures, that bind two or more different targets simultaneously. Bycytokines in a variety of formats, and we recently introduced CD3 bispecific antibodies of a mixed valency format, the XmAb 2+1 bispecific antibody. XmAb 2+1 bispecific antibodies may preferentially kill tumor cells with high target expression, which may be especially beneficial in designing antibodies that target solid tumors. This selectivity potentially empowers CD3 bispecifics to address an expanded set of tumor antigens. Our lead XmAb 2+1 bispecific antibody candidate is XmAb819, a first-in-class ENPP3 x CD3 bispecific antibody. ENPP3 is a tumor-associated antigen in renal cell carcinoma (RCC) and exhibits low level expression on normal tissues. We presented preclinical data from this program and two other protein moleculesXmAb 2+1 bispecific antibody programs at the AACR Virtual Annual Meeting II in June 2020, and we plan to submit an IND application for XmAb819 in 2021.
58
Additionally, we have engineered CD28 bispecific antibodies to provide conditional CD28 co-stimulation of T cells, activating them when bound to tumor cells. Targeted CD28 bispecific antibodies may provide conditional co-stimulation of T cells, for example, to T cells recognizing neoantigens or in concert with improved function,CD3 T-cell engaging bispecific antibodies. Our CD28 platform is also the subject of our collaboration with Janssen Biotech, Inc., announced in December 2020, where we believe thatare creating and characterizing CD28 bispecific antibody candidates against a prostate tumor target specified by Janssen. We are also advancing our XmAb‑engineered proteins offer innovative approacheswholly owned CD28 candidates including our lead candidate, a B7-H3 x CD28 bispecific antibody designed to treating diseasebe evaluated for the treatment of patients with a range of solid tumors, and potential clinical advantages over other treatments.it is currently advancing through preclinical development. We presented preclinical data from the CD28 program at the SITC Annual Meeting in November 2020.
OurProgress Across Partnerships
A key part of our business strategy is to leverage our protein engineering capabilities, XmAb technologies and drug candidates with partnerships, collaborations and licenses. Through these arrangements we generate revenues in the form of upfront payments, milestone payments and royalties. For partnerships for our drug candidates, we aim to retain a major economic interest in the form of keeping major geographic commercial rights; profit-sharing; co-development options; and the right to conduct studies with drug candidates developed in the collaboration. The types of arrangements that we have entered with partners include product licenses, novel bispecific antibody collaborations, technology licensing agreements and strategic collaborations.
Product Licenses
Product licenses are arrangements in which we have internally developed drug candidates and, based on a strategic review, licensed partial or full rights to third parties to continue development and potential commercialization. We seek partners that can provide infrastructure and resources to successfully develop our drug candidates, have a track record of successfully developing and commercializing medicines, or have a portfolio of development-stage candidates and commercialized medicines which could potentially be developed in rational combinations with our drug candidates.
The U.S. FDA approved Monjuvi (tafasitamab-cxix), the plug‑and‑play nature of thesecond product with XmAb technology allowing us to create newbe approved for commercial marketing, in July 2020. Monjuvi is a CD19-directed cytolytic antibody indicated in combination with lenalidomide for the treatment of certain adult patients with relapsed or refractory DLBCL, and it was created and initially developed by us. Monjuvi is co-commercialized in the U.S. by MorphoSys and Incyte. The European Marketing Authorization Application for tafasitamab is currently under review by the European Medicines Agency. In 2020, we earned a total of $37.5 million in regulatory milestones and royalties of $1.5 million on net sales of Monjuvi.
In February 2020, we granted Aimmune Therapeutics, Inc., subsequently acquired by Nestlé S.A., an exclusive worldwide license to develop and commercialize the investigational humanized monoclonal antibody XmAb7195, which has been renamed AIMab7195. Aimmune indicated plans to develop AIMab7195 as an adjunctive treatment with its pipeline of oral immunotherapies to explore treatment outcomes in patients with food allergies. Nestlé is solely responsible for costs related to the development and potential commercialization of AIMab7195, and additional studies of AIMab7195 are planned. In 2020, Xencor received an upfront payment of $9.6 million in cash and Aimmune stock.
In October 2020, a second IL-15 cytokine candidate, which is engineered with a target-specific binding arm, was approved for further preclinical exploration under our Genentech collaboration. As a Collaboration Product under the agreement, we share in 45% of development and commercialization costs, while Genentech will pay for commercial launch costs, and we will receive a 45% share of net profits from sales from all collaboration products, while also sharing in the net losses at the same percentage rate. We are eligible to receive up to $180.0 million in clinical milestone payments for this candidate.
59
In November 2020, we entered into an agreement with a newly formed, privately held biotechnology company to which we licensed the exclusive worldwide rights to develop and commercialize three preclinical-stage Fc-engineered drug candidates for autoimmune disease: XmAb6755, XPro9523 and XmAb10717. These programs incorporate an Xtend Fc Domain, a Cytotoxic Fc Domain, or both. We received a 15% equity interest in the company, and we will also receive royalties on net sales of approved products in the mid-single digit to mid-teen percentage range.
Novel Bispecific Antibody Collaborations
Novel bispecific antibody collaborations are arrangements in which our internalpartner seeks to create a bispecific antibody using one or more of our XmAb bispecific technologies. Our partners provide an antibody or a tumor-associated antigen, and we conduct limited research and development orto create potential bispecific antibody candidates for further development and commercialization by our partners.
In November 2020, we entered an agreement with Janssen Biotech, Inc., focused on the discovery of XmAb bispecific antibodies against CD28, an immune co-stimulatory receptor on T cells, and an undisclosed prostate tumor target, for the potential treatment of patients with prostate cancer. Additionally, we have a right to access select, predefined agents from Janssen’s portfolio of clinical-stage drug candidates and commercialized medicines to evaluate potential combination therapies in prostate cancer with agents in our own pipeline, subject to some limitations. Janssen has the same right with our portfolio to evaluate potential combination therapies in prostate cancer, as well. The ability to study combinations of therapies from both companies’ prostate cancer portfolios leverages our broad clinical pipeline and Janssen's leading prostate cancer therapeutics portfolio. In 2020, we received a $50 million upfront payment from Janssen.
In 2020, we received a $2.5 million milestone payment related to our agreement with Astellas Pharma, Inc., which has advanced an XmAb bispecific candidate into IND enabling studies. Under our March 2019 agreement with Astellas, we applied our XmAb bispecific Fc technology to an antigen pair provided by Astellas and generated bispecific antibody candidates for further development by Astellas. In 2019, we completed delivery of the bispecific candidates to Astellas for further development and potential commercialization.
Other XmAb bispecific antibodies being developed by our partners include Amgen's AMG 509, a STEAP1 x CD3 XmAb 2+1 bispecific antibody, which being evaluated in a Phase 1 study for patients with prostate cancer, and an undisclosed bispecific antibody candidate being developed by Novartis, which is also in Phase 1 development.
Technology License Agreements
We enter into technology licensing or to selectivelyagreements in which we license access to one or more of our XmAb Fc technologies on a restricted basis, typically to pharmaceutical an XmAb Cytotoxic Fc Domain and/or biotechnology companies to use in developing their own proprietary antibodies with improved properties.the Xtend Fc Domain. Our protein engineering capabilitiespartners are responsible for all research, development and commercialization activities of the modulardrug candidates. The plug-and-play nature of our technologyXmAb technologies allows us to quickly identify and create multiple drug candidates for potential development. We have appliedlicense access to our XmAb technology to:
|
|
|
|
60
|
|
Our many partnerships and licensing transactions provide usplatforms with multiple revenue streams that help fund development of our product candidates and usually require limited resources or efforts from us. In 2018, we received $20.5 million in milestones from our partners and in February 2019, we announced a collaboration with Genentech for which we will receive an upfront payment of $120 million. There are currently 12 antibody product candidates in clinical trials that have been engineered with XmAb technology, two additional candidates have IND applications allowed by the FDA and will begin Phase 1 trials in 2019, and two more programs are in the preclinical stage of development.
In December 2018, the FDA approved the first antibody that incorporates our Fc technology. ALXN1210, now Ultomiris™, was approved by the United States Food and Drug Administration (FDA) for commercial marketing. Ultomiris is a complement inhibitor indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH), that is being developed by our partner Alexion, and incorporates our Xtend® Fc technology which allows for longer duration of action and less frequent dosing regimens compared to the previously approved therapy, Soliris®. There are five additional clinical candidates being advanced by licenseesno internal research and development partners.activities.
We have created a suite of compounds developed from our XmAb bispecificAlexion’s Ultomiris uses Xtend Fc domains that we wholly-own or are developing with our partners. These bispecific Fc domains are used to generate a broad array of novel drug candidates.
The initial bispecific candidates that we designed were created with our engineered heterodimer Fc domain, or bispecific Fc domain, and are dual-antigen targeting molecules, containing an anti-tumor associated antigen binding domain and a second binding domain targeted to CD3, an activating receptor on T-cells. We are advancing three CD3 bispecific candidates through clinical development: XmAb14045, XmAb13676, and XmAb18087.
|
|
It is being developed in collaboration with our partner Novartis and is being evaluated in a Phase 1 study in patients with relapsed or refractory acute myeloid leukemia (AML). We presented initial data from the study in December 2018 at ASH. The data presented indicated multiple complete responses had been achieved with weekly dosing of XmAb14045 in this heavily-pretreated patient population. 28% of evaluable AML patients achieved either a complete remission (CR) or CR with incomplete homological recovery (CRi) at the two highest dose levels studies to date.
In February 2019, we received notice from the FDA placing the XmAb14045 study on partial clinical hold due to safety issues of cytokine release syndrome and pulmonary toxicities. Under the partial hold, existing subjects on the trial may continue to receive dosing; however, no new subjects may be enrolled pending FDA review of a clinical hold response.
The partial hold was initiated following recent safety reports Xencor submitted to the FDA on two patient deaths that were considered at least possibly related to XmAb14045. One patient experienced cytokine release syndrome (CRS) after their first dose, the treatment of which was complicated by the patient’s decision to withdraw care. One subject developed acute pulmonary edema following several doses of XmAb14045. Items to be addressed in the response include analysis of CRS cases per dosing level, efficacy information, and strategies to mitigate the observed toxicities.
We are coordinating a response to the partial hold by the FDA with our partner, Novartis, and plan to continue development of XmAb14045 pending resolution of the partial hold.
61
|
|
|
|
We are also advancing into clinical development a suite of tumor microenvironment activators that have been designed to promote tumor-selective T-cell activation by targeting multiple checkpoint or co-stimulatory receptors. We are advancing three TME activator candidates through clinical development: XmAb20717, XmAb22841, and XmAb23104:
|
|
|
|
|
|
In 2018, we expanded our bispecific Fc platform with the design of our novel cytokine candidates. These cytokines are built on our bispecific Fc domain and have potency tuned to improve therapeutic index. These candidates also incorporate our Xtend technology for longer duration of action. Our first cytokine candidate is XmAb24306, an IL15/IL15-receptior alpha complex fused to a bispecific domain (IL15/IL15Ra-Fc). We believe that IL-15 cytokines, like XmAb24306, will be an optimal candidate for oncology combination therapies.
|
|
We have also created a suite of wholly-owned compounds using our Immune Inhibitor Fc Domain.
62
|
|
In October 2018, we presented topline datahalf-life. Ultomiris has received marketing authorizations from the Phase 2 study of XmAb5871 in patients with SLE at the American College of Rheumatology (ACR) annual meeting. The primary endpoint of the study was the proportion of patients with no loss of improvement (LOI) (i.e. maintenance of improvement) in the efficacy-evaluable population. Improvement was maintained at Day 225 by 42% of patients in the XmAb5871-treated arm, compared to 28.6% of patients in the placebo-treated arm, which did not meet the primary endpoint for statistical significance.
The SLE study did meet secondary endpoints included evaluations of time to LOI. Patients in the efficacy-evaluable population treated with XmAb5871 experienced a statistically significant longer time to LOI, compared to placebo-treated patients, which represented a 76% improvement in median time to LOI and a 47% reduction in risk of LOI. XmAb5871 was well tolerated, and its safety profile was consistent with previous trials.
In November 2017 we presented final data from the IgG4-RD Phase 2 trial at the ACR annual meeting.
We have also completed an additional Phase 1 trial for a subcutaneous formulation of XmAb5871.
We believe that the data from the studies of XmAb5871 in patients with SLE and IgG4-RD support further development in these indications and show the potential of XmAb5871 in other B-cell mediated autoimmune indications. We are seeking to partner XmAb5871 with a partner that has the infrastructure and resources to continue late-stage development of XmAb5871 and maximize the potential of this candidate for a broad set of patient populations.
|
|
We have also created antibodies which we have licensed to other pharmaceutical and biotechnology companies for further development. These include MOR208, an antibody in Phase 3 development, which we licensed to MorphoSys, and a CD38 x CD3 bispecific antibody candidate which included XmAb13551 and antibody components used to assemble AMG424, which we licensed to Amgen. In 2017 MorphoSys advanced MOR208 into a Phase 3 clinical trial and MorphoSys has indicated plans to file a BLA in the U.S. in 2019. Amgen has started a Phase 1 study for AMG424 and also has a preclinical candidate, AMG509, that was created with our bispecific Fc domain, advancing into development. There are currently five other programs where we have licensed our technology to partners for use in development programs with their own molecules, and four of these programs are in clinical development. The most advanced is Ultomiris, formerly ALXN1210. In 2018, Alexion submitted marketing authorization applications for Ultomiris to the regulatory authoritiesagencies in the U.S., Europe and Japan for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) and for patients with atypical hemolytic uremic syndrome (aHUS). Alexion is also evaluating Ultomiris in a broad late-stage development program across many indications in neurology and nephrology. In 2020, we earned $16.2 million in royalties and $10.0 million in sales-based milestone payments from Alexion.
In January 2020, we entered an agreement with Gilead Sciences, Inc., under which Gilead has access to our Xtend and Cytotoxic XmAb Fc technologies for developing and commercializing elipovimab (GS-9722), Gilead’s effector-enhanced broadly neutralizing anti-HIV antibody, as well as up to three additional anti-HIV antibodies. In 2020, Gilead exercised all three options. Gilead has advanced elipovimab and GS-9723 into Phase 1 clinical studies. In 2020, we received $13.5 million in upfront and option payments from Gilead.
60
In March 2020, we entered a second agreement with Vir Biotechnology, Inc., under which Vir has non-exclusive access to our Xtend Fc technology to extend the half-life of novel antibodies being investigated as potential treatments for patients with COVID-19, as well as prophylactic use against infection from the SARS-CoV-2 virus. Vir has commenced a Phase 3 clinical study of VIR-7831 for the early treatment of COVID-19 patients who are at high risk of hospitalization and has indicated plans to initiate a clinical study of VIR-7832 in the near future.
In August 2020, we entered into an agreement with Omeros Corporation, under which we provided Omeros a non-exclusive license to access our Xtend Fc technology, an exclusive license to apply Xtend Fc technology to an identified antibody and options to apply Xtend Fc technology to three additional antibodies. In 2020, we received an upfront payment of $5.0 million from Omeros.
In December 2018, Alexion2020, we entered into an agreement with MiRagen Therapeutics, Inc., in which we provided MiRagen a non-exclusive license to our Xtend Fc technology and an exclusive license to apply our Xtend Fc technology to antibodies targeting IGF-1R. MiRagen subsequently changed its name to Viridian Therapeutics, Inc. We received FDA approval.an upfront payment of 322,407 shares of Viridian common stock valued at $6.0 million.
Strategic Collaborations
We have over 750 issuedenter into strategic collaborations where we can create synergies between our partners' strengths and pending patents worldwide to protectassets and our own protein engineering capabilities, XmAb technology platformtechnologies and XmAb drug candidates. Through these arrangements we seek to create new drug candidates, investigate novel combination therapies and potentially identify additional indications for our portfolio of XmAb drug candidates.
63
costs and profits. Each company has the option to lead development, regulatory and commercialization activities for one of the two joint programs. In addition, the agreement allows each partner the option to pursue up to two programs independently, with a mid- to high-single digit percent royalty payable on net sales to the other partner.
Key Company MilestonesIn September 2020, we entered an agreement with The University of Texas MD Anderson Cancer Center, under which we will design and execute new investigator-sponsored clinical studies with our portfolio of XmAb drug candidates. We are committing $10.0 million in funding and supporting these studies over an initial five-year term.
Genentech Collaboration: In February 2019,November 2020, we entered the clinical collaboration with MorphoSys and Incyte to investigate the combination of plamotamab, tafasitamab and lenalidomide in patients with relapsed or refractory DLBCL, first-line DLBCL and relapsed or refractory follicular lymphoma (FL).
In December 2020, we entered into a research and licensesecond agreement with Genentech (Genentech Agreement)MD Anderson to develop novel CD3 bispecific antibody therapeutics for the potential treatment of patients with cancer. MD Anderson will work to identify and develop potential antibodies, and we will apply its our Fc bispecific technology to create therapeutic candidates. MD Anderson will then conduct and fund all preclinical activities to advance candidates toward clinical studies. We have certain exclusive options to license worldwide rights to develop and commercialize novel IL-15 cytokine therapeutics that use our bispecific Fc technology, including XmAb24306, inpotential new medicines arising from the areascollaboration.
Refer to Part IV, Item 15, Note 10, "Collaboration and Licensing Agreements" of cancer immunotherapy. We will jointly collaborate on the worldwide development of XmAb24306 and other IL-15 cytokine therapeutics, each a “Collaboration Product” with Genentech maintaining worldwide commercialization rights, subject to us having a co-promotion option in the U.S. We retained the right to perform clinical studies of Collaboration Products in combination with other therapeutic agents, subject to certain requirements. Genentech received a worldwide exclusive license to the XmAb24306 and other Collaboration Products.
Under the Genentech Agreement, we will receive an upfront payment of $120 million and are eligible to receive up to $160 million in clinical milestone payments for each Collaboration Product that advances to Phase 3 clinical trials. We are eligible to receive a 45% share of net profits from sales of XmAb24306 and other Collaboratio Products, while also sharing in the net losses at the same percentage rate and we will jointly share in 45% of development and commercialization costs. We will conduct a two-year joint research program with Genentech to discover additional programs around the IL-15 cytokine technology and will receive a $20 million milestone payment upon the initiation of each Phase 1 clinical trial for each new Collaboration Product developed under a research plan.
The Genentech Agreement is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act, and closing is expected to occur in the first quarter of 2019.
Novartis Collaboration. In June 2016, we entered into a Collaboration and License Agreement with Novartis (Novartis Agreement) to develop and commercialize bispecific and other Fc engineered antibody drug candidates using the Company’s proprietary XmAb technologies and drug candidates. Under the Novartis Agreement, we licensed certain rightsnotes to our two lead bispecific candidates, XmAb14045 and XmAb13676, to Novartis including the rightconsolidated financial statements included in this Annual Report on Form 10-K for Novartis to commercialize drug products from both programs in all worldwide territories outside the U.S. We are co-developing XmAb14045 worldwide and sharing development costs equally. We will also apply our bispecific technology to up to four Novartis identified antibodies and will also license other Fc technologies to Novartis. We received a non-refundable upfront payment of $150 million and are eligible to receive up to $2.1 billion in milestone payments under the Novartis Agreement.
In December 2018, Novartis notified us of its decision to return its rights with respect to the XmAb13676 program. Novartis will continue to fund its share of development costs for the XmAb13676 program through June 2020 and we plan to continue developmentdescription of the program.
Licensing Partnerships. In addition to Novartis and Genentech collaborations, we have four other licensing partnerships for the licensingkey terms of our XmAb technology. These arrangements provide research funding, upfront payments and annual licensing fees in addition to potential milestones and contractual payments as our partners advance compounds that incorporate our technology through clinical development.
During 2018, Alexion submitted regulatory filings for Ultomiris in the U.S., European Union and Japan. In December 2018, Alexion received approval from the FDA for the treatment of adult patients with PNH. We received a total of $20 million in regulatory milestone payments from Alexion for Ultomiris in 2018. In November 2018, Amgen began preclinical studies for AMG509, for intended clinical development for patients with prostate cancer, and we received a $0.5 million milestone payment.
Bispecific Fc programs. We continue to advance our pipeline with bispecific Fc antibodies and cytokines that incorporate our XmAb bispecific Fc domain, which allow us to create molecules that bind to multiple different targets. By using an Fc as an integral part of the molecule, we impart the advantages of natural antibody features, including enabling it to retain or enhance favorable half-life, simplifying manufacturing processes and modulating potency to reduce toxicity.
arrangements.
6461
We have initiated the Phase 1 trials for four bispecific oncology candidates: XmAb14045, XmAb13676, XmAb18087, and XmAb20717. We have received FDA approval of our IND applications for our next two candidates, XmAb22841 and XmAb23104, and we will be initiating Phase 1 trials in the first half of 2019. We are in preclinical development for our first bispecific Fc domain cytokine candidate, XmAb24306, and we plan to submit an IND for this candidate in the second half of 2019.
In March 2018, we completed the sale of 8,395,000 shares of common stock in an underwritten follow-on financing and raised net proceeds of $245.5 million after deducting underwriters’ commissions and expense of the sale.
Financial Operations Overview
Revenues
Our revenues to date have been generated primarily from our collaboration agreements, our product licensing agreements, and our technology licensing agreements. Revenue recognized from our collaboration and product licensing agreements includes non-refundable upfront payments, and milestone payments and royalties on net sales of approved products while revenue from our technology licensing agreements includes upfront payments, annual maintenance fees, option payments to obtain commercial licenses, milestone payments and milestone payments.royalties on net sales of approved products. Since our inception through December 31, 2018,2020, we have generated $266.2$545.6 million in revenues under the various product development partnership and technology license arrangements. Several of our product development partnership and technology license agreements provide us the opportunity to earn future milestone payments, royalties on product sales and option exercise payments.
Summary of Collaboration and Licensing Revenue by Partner
The following is a comparison of collaboration, product licensing and technology licensing revenue for the years ended December 31, 2018, 20172020, 2019 and 20162018 (in millions):
|
|
|
|
|
|
|
|
|
|
| ||||||||||
|
| Year Ended |
| |||||||||||||||||
|
| December 31, |
| |||||||||||||||||
|
| 2018 |
| 2017 |
| 2016 |
| |||||||||||||
|
|
|
|
| (As Revised) |
| (As Revised) |
| ||||||||||||
| | | | | | | | | | | ||||||||||
| | Year Ended |
| |||||||||||||||||
| | December 31, |
| |||||||||||||||||
| | 2020 | | 2019 | | 2018 |
| |||||||||||||
Aimmune |
| $ | 9.6 |
| $ | — |
| $ | — | | ||||||||||
Amgen |
| $ | 0.6 |
| $ | 10.0 |
| $ | 31.2 |
| | | — | | | 5.0 | | | 0.6 | |
Alexion |
|
| 20.0 |
|
| — |
|
| 5.0 |
| | | 26.2 | |
| 13.0 | |
| 20.0 | |
CSL |
|
| — |
|
| 3.5 |
|
| — |
| ||||||||||
Astellas | | | 3.5 | | | 14.0 | | | — | | ||||||||||
Genentech | | | 3.5 | | | 113.9 | | | — | | ||||||||||
Gilead | | | 13.5 | | | — | | | — | | ||||||||||
MiRagen/Viridian | | | 6.0 | | | — | | | — | | ||||||||||
MorphoSys |
|
| — |
|
| 12.5 |
|
| — |
| | | 39.0 | | | — | | | — | |
Novo Nordisk |
|
| — |
|
| — |
|
| 2.7 |
| ||||||||||
Novartis |
|
| 20.0 |
|
| 20.1 |
|
| 69.9 |
| | | — | | | 10.0 | | | 20.0 | |
Other |
|
| — |
|
| 0.1 |
|
| 0.2 |
| ||||||||||
Omeros | | | 5.0 | | | — | | | — | | ||||||||||
Vir | | | 0.3 | | | 0.8 | | | — | | ||||||||||
Private BioCo | | | 16.1 | |
| — | |
| — | | ||||||||||
Total |
| $ | 40.6 |
| $ | 46.2 |
| $ | 109.0 |
| | $ | 122.7 | | $ | 156.7 | | $ | 40.6 | |
65
Research and Development Expenses
ResearchThe following is a comparison of research and development expenses for the years ended December 31, 2020, 2019, and 2018 (in millions):
| | | | | | | | | |
| | Year Ended | |||||||
| | December 31, | |||||||
| | 2020 | | 2019 | | 2018 | |||
External research and development expenses |
| $ | 94.2 |
| $ | 52.2 |
| $ | 48.2 |
Internal research and development expenses | | | 54.7 | | | 43.4 | | | 36.5 |
Stock based compensation | | | 20.9 | |
| 23.0 | |
| 12.8 |
Total | | $ | 169.8 | | $ | 118.6 | | $ | 97.5 |
62
Internal research and development expenses consist primarily of salaries, benefits, stock‑based compensation and related personnel costs, supplies, and allocated overhead including facility costscosts. External research and development expenses include preclinical testing costs, clinical trial costs and fees paid to external service providers. External service providers include contract research organizations (CRO) and contract manufacturing organizations (CMO) to conduct clinical trials, manufacturing and process development, IND‑enablingIND-enabling toxicology testing and formulation of clinical drug supplies. We expense research and development expenses as incurred. We account for nonrefundable advance payments for goods and services that will be used in future research and development activities as expense when the service has been performed or when the goods have been received. We estimate contract manufacturing, preclinical study and clinical trial expenses based on the services performed pursuant to the contracts with manufacturing, research institutions and clinical research organizations that manufacture and conduct and manage preclinical studies and clinical trials on our behalf based on the actual time and expenses incurred by them. We accrue expenses related to clinical trials based on the level of patient enrollment and activity according to the related agreement. We monitor patient enrollment levels and related activity to the extent reasonably possible and adjust estimates accordingly. Our estimates of clinical trial expense have fluctuated on a period‑to‑periodperiod-to-period basis due to changes in the stage of the clinical trials and patient enrollment levels. We expect to experience a continuing pattern of fluctuations in clinical trial expenses as current clinical trials are completed and as we initiate additional and later stage clinical trials. To date, we have not experienced significant differences between our periodic estimates of clinical trial expense and the actual costs incurred. We expect changes in future clinical trial expenses to be driven by changes in service provider costs and changes in clinical stage and patient enrollment. We have incurred a total of $466.1 million in research and development expenses from inception through December 31, 2018.
We expect that our future research and development expenses maywill increase over spendingoverspending levels in recent years if we are successful in advancing XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104, XmAb24306,our current clinical-stage drug candidates or any of our other preclinical programs into advancedlater stages of clinical development. The process of conducting preclinical studies and clinical trials necessary to obtain regulatory approval is costly and time‑consuming.time-consuming. We or our partners may never succeed in achieving marketing approval for any of our product candidates. Numerous factors may affect the probability of success for each product candidate, including preclinical data, clinical data, competition, manufacturing capability, approval by regulatory authorities and commercial viability.
Our research and development operations are conducted such that design, management and evaluation of results of all of our research and development is performed internally, while the execution of certain phases of our research and development programs, such as toxicology studies in accordance with Good Laboratory Practices (GLP), and manufacturing in accordance with current Good Manufacturing Practices (cGMP), is accomplished using CROs and CMOs. We account for research and development costs on a program‑by‑programprogram-by-program basis except in the early stages of research and discovery, when costs are often devoted to identifying preclinical candidates and improving our discovery platform and technologies, which are not necessarily allocable to a specific development program. We assign costs for such activities to distinct projects for preclinical pipeline development and new technologies. We allocate research management, overhead, commonly used laboratory supplies and equipment, and facility costs based on the numberpercentage of full‑time of full-time research personnel allocated toefforts on each program.
6663
The following is a comparison of research and development expenses for the years ended December 31, 2018, 20172020, 2019 and 20162018 (in millions):
|
|
|
|
|
|
|
|
|
|
|
|
| Year Ended |
| |||||||
|
| December 31, |
| |||||||
|
| 2018 |
| 2017 |
| 2016 |
| |||
Product programs: |
|
|
|
|
|
|
|
|
|
|
XmAb5871 programs |
| $ | 23.0 |
| $ | 20.3 |
| $ | 17.3 |
|
XmAb7195 program |
|
| 0.8 |
|
| 3.4 |
|
| 7.5 |
|
Bispecific programs |
|
|
|
|
|
|
|
|
|
|
CD-3 |
|
| 23.1 |
|
| 21.3 |
|
| 17.9 |
|
TME checkpoints |
|
| 33.1 |
|
| 20.7 |
|
| 5.8 |
|
Cytokines |
|
| 7.7 |
|
| — |
|
| — |
|
Subtotal Bispecific programs |
|
| 63.9 |
|
| 42.0 |
|
| 23.7 |
|
Other, research and early stage programs |
|
| 9.8 |
|
| 6.1 |
|
| 3.4 |
|
Total research and development expenses |
| $ | 97.5 |
| $ | 71.8 |
| $ | 51.9 |
|
| | | | | | | | | | |
| | Year Ended |
| |||||||
| | December 31, |
| |||||||
| | 2020 | | 2019 | | 2018 |
| |||
Product programs: |
| | |
| | |
| | |
|
Obexelimab (XmAb5871) |
| $ | 2.9 | | $ | 17.5 | | $ | 23.0 | |
| | | | | | | | | | |
Bispecific programs: | | | | | | | | | | |
CD3 programs: | | | | | | | | | | |
Vibecotamab* | | | 12.4 | | | 11.6 | | | 9.3 | |
Plamotamab | | | 33.8 | | | 12.3 | | | 5.6 | |
Tidutamab | | | 14.9 | | | 11.4 | | | 7.8 | |
XmAb819 (ENPP3 x CD3) | | | 7.4 | | | 0.5 | | | — | |
Total CD3 programs | | | 68.5 | | | 35.8 | | | 22.7 | |
| | | | | | | | | | |
Tumor microenvironment (TME) activator programs: | | | | | | | | | | |
XmAb717 | | | 26.4 | | | 13.0 | | | 8.7 | |
XmAb104 | | | 13.3 | | | 7.8 | | | 14.5 | |
XmAb841 | | | 10.6 | | | 7.4 | | | 9.9 | |
Total TME activator programs | | | 50.3 | | | 28.2 | | | 33.1 | |
| | | | | | | | | | |
Cytokine programs: | | | | | | | | | | |
XmAb306/RG6323* | | | 12.0 | | | 17.0 | | | 7.7 | |
XmAb564 | | | 15.4 | | | 5.0 | | | — | |
Total cytokine programs | | | 27.4 | | | 22.0 | | | 7.7 | |
| | | | | | | | | | |
Subtotal bispecific programs | | | 146.2 | | | 86.0 | | | 63.5 | |
| | | | | | | | | | |
Other, research and early stage programs | | | 20.7 | |
| 15.1 | | | 11.0 | |
| | | | | | | | | | |
Total research and development expenses |
| $ | 169.8 | | $ | 118.6 | | $ | 97.5 | |
*Includes net payments to, and reimbursements from our partners pursuant to agreements that include cost-sharing arrangements.
General and Administrative Expenses
General and administrative expenses consist primarily of salaries and related benefits, including stock‑basedstock-based compensation related to our executive, finance, business development, and support functions. Other general and administrative expenses include rent and utilities, travel expensesintellectual property costs, facility costs, and professional fees for auditing, tax and legal services.
Other Income, Net
For the years ended December 31, 2018, 20172020, 2019 and 2016,2018, other income, net consists primarily of interest income from our investments during the years.
Critical Accounting Policies, Significant Judgments and Estimates
Our management’s discussion and analysis of our financial condition and results of operations is based on our financial statements, which have been prepared in accordance with accounting principles generally accepted in the United States (GAAP). The preparation of our financial statements in conformity with GAAP requires our management to make estimates and assumptions that affect the amounts and disclosures reported in the financial statements and
64
accompanying notes. Actual results could differ materially from those estimates. Our management believes judgment is involved in determining revenue recognition, the fair value‑basedvalue-based measurement of stock‑basedstock-based compensation, the fair value estimate of marketable securities, the capitalization and recoverability of intellectual property costs, valuation of deferred tax assets and accruals. Our management evaluates estimates and assumptions as facts and circumstances dictate. As future events and their effects cannot be determined with precision, actual results could differ from these estimates and assumptions, and those differences could be material to the financial statements. If our assumptions change, we may need to revise our estimates, or take other corrective actions, either of which may also have a material adverse effect on our statements of operations, liquidity and financial condition.
While our significant accounting policies are described in more detail in Note 1 to our financial statements included elsewhere in this Annual Report, on Form 10‑K, we believe the following accounting policies to be critical to the judgments and estimates used in the preparation of our financial statements.
Revenue Recognition
We have, to date, earned revenue from research and development collaborations, which may include research and development services, licenses of our internally-developedinternally developed technologies, licenses of our internally-developedinternally developed drug candidates, or combinations of these.
67
The terms of our license and research and development and collaboration agreements generally include non-refundable upfront payments, research funding, co-development reimbursements, license fees, and milestone and other contingent payments to us for the achievement of defined collaboration objectives and certain clinical, regulatory and sales‑basedsales-based events, as well as royalties on sales of any commercialized products.
The terms of our licensing agreements include non‑refundablenon-refundable upfront fees, annual licensing fees, and contractual payment obligations for the achievement of pre‑definedpre-defined preclinical, clinical, regulatory and sales‑basedsales-based events by our partners. The licensing agreements also include royalties on sales of any commercialized products by our partners.
As described in “Recent Accounting Pronouncements” in the notes to the financial statements included in this Annual Report on Form 10-K, effective January 1, 2018, the Company adopted ASC 606. Subsequent to the adoption, the Company recognizes revenue through the five-step process in accordance with ASC 606 Revenue Recognition when control of the promised goods or services is transferred to our customers in an amount that reflects the consideration we expect to be entitled to in exchangeIn certain transactions for those goods or services.
The Company used the full retrospective method and as a result the Company has revised its comparative financial statements for the prior period as if ASC 606 had been in effect for that period.
The most significant changes to revenue recognition under ASC 606 relate to the timing of revenue recognized for arrangements that include licensing of our technologies. Under ASC 606 revenue relatedtechnologies or our product candidates, we may receive an equity interest from our partners as full or partial consideration for an upfront payment due under the arrangement. We record the initial equity at its fair value and mark the value to licensing of access to our technologiesmarket quarterly for publicly traded securities and review for impairment for equity that is recognized at inception of the agreement, generally the effective date of the agreement. For existing licensing arrangements, the effect of ASC 606 is to shift revenue to earlier periods. Approximately $11.3 million of licensing revenue that was being recognized over the five-year period 2016-2021 is being recognized in the second quarter of 2016.not publicly traded on a national exchange.
The other significant change under ASC 606 relates to the timing of collaboration revenue when the Company completes its performance obligations for delivery of a drug candidate to its collaboration partners after applying its technologies. For existing collaborations, the effect of ASC 606 is to accelerate revenue recognition to earlier periods. Approximately $6.25 million of collaboration revenue recognized in 2017 and 2018 under historical accounting guidance is being recognized in 2016 under ASC 606. An additional $20.5 million of collaboration revenue that would be recognized in 2018 is being recognized in 2017.
Capitalized Intellectual Property Costs
We capitalize and amortize third‑partythird-party intellectual property costs such as amounts paid to outside patent counsel for filing, prosecuting and obtaining patents for our internally developed technologies and product candidates, to the extent such patents are deemed to have probable future economic benefit. We also capitalize amounts paid to third parties for licenses that we acquire for intellectual property or for research and development purposes.purposes where the technology has alternative uses. The net capitalized patents, licenses and other intangible assets as of December 31, 20182020 and 20172019 was $12.0$16.0 million and $11.1$14.4 million, respectively. We believe that these costs should be capitalized as the intellectual property portfolio iscreates the underlying property right to our technologies and product candidates and supports the upfront payments, licensing fees, and milestone payments and royalties made by our collaboration partners for licensing our technologies and product candidates.
We begin amortization of capitalized patent costs during the period that we obtain a patent relating to the capitalized cost over the shorter of the patent life or the estimated economic useful life. Capitalized licensing costs are amortized beginning in the period that access to the license or technology is available and is amortized over the shorter of the license term or the estimated economic useful life of the licensed asset. Such amortization is reflected in the Generalrecorded as general and Administrative section of our Statement of Comprehensive Income (Loss).
68
administrative expenses.
On a regular basis we review the capitalized intellectual property portfolio and determine if there have been changes in the scientific or patent landscape that leads us to decide to abandon an in‑processin-process patent application or abandon a previously issued patent. While we confer with outside patent counsel, the decision to continue prosecuting
65
certain patent claims or abandon other claims are made by us based on our judgment and existing knowledge of our technology, current U.S. and foreign patent authority rulings and expected rulings, and scientific advances and patent filings by competitors operating in our technology or drug development field. We record an expense for the write-off of capitalized intangible assets in the period that the decision to abandon a claim or license is made. We also review the carrying value of capitalized licensing costs on a regular basis to determine if there have been any changes to the useful life or estimated amortization period over which the costs should be amortized. We recorded a charge for abandoned intangible assets of $0.5 million, $0.2 million $0.4 million and $0.4$0.2 million for the years ended December 31, 2018, 20172020, 2019 and 2016,2018, respectively. Such charges are reflected in the Generalas general and Administrative section of our Statement of Comprehensive Income (Loss).administrative expenses.
We determine if there has been an impairment of our intangible assets which include the capitalized patent and licensing costs whenever events such as recurring operating losses or changes in circumstances indicate that the carrying amount of the assets may not be recoverable.
Accrued Research and Development Expenses
As part of the process of preparing our financial statements, we are required to estimate our accrued research and development expenses. This process involves reviewing contracts and purchase orders, reviewing the terms of our license agreements, communicating with our applicable personnel to identify services that have been performed on our behalf, and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of actual cost. The majority of our service providers invoice us monthly in arrears for services performed. We make estimates of our accrued expenses as of each balance sheet date based on facts and circumstances known to us at that time. We periodically confirm the accuracy of our estimates with the service providers and make adjustments if necessary. Examples of estimated accrued research and development expenses include fees to:
|
|
| contract manufacturers in connection with the production of and testing of clinical trial materials; and |
| vendors in connection with preclinical development activities. |
We base our expenses related to clinical studies on our estimates of the services received and efforts expended pursuant to contracts with multiple research institutions and contract research organizations that conduct and manage clinical studies on our behalf. The financial terms of these agreements are subject to negotiation, vary from contract to contract, and may result in uneven payment flows and expense recognition. Payments under some of these contracts depend on factors such as the successful enrollment of patients and the completion of clinical trial milestones. In accruing these costs, we estimate the time period over which services will be performed for which we have not been invoiced and the level of effort to be expended in each period. If the actual timing of the performance of services or the level of effort varies from our estimate, we adjust the accrual accordingly. Our understanding of the status and timing of services performed relative to the actual status and timing of services performed may vary and may result in our reporting changes in estimates in any particular period.
69
Income Taxes
Deferred tax assets and liabilities are determined based on differences between the financial reporting and tax basis of assets and liabilities and are measured using the enacted tax rates and laws that are expected to be in effect when the differences are expected to reverse. The effect on deferred tax assets and liabilities of a change in tax rates is recognized as income in the period that such tax rate changes are enacted. The measurement of a deferred tax asset is reduced, if necessary, by a valuation allowance if it is more likely than not that some portion or all of the deferred tax asset will not be realized. Financial statement recognition of a tax position taken or expected to be taken in a tax return is determined based on a more-likely-than not threshold of that position being sustained. If the tax position meets this threshold, the benefit to be recognized is measured as the largest amount that is more than 50% likely to be realized upon ultimate settlement. Our policy is to record interest and penalties related to uncertain tax positions as a component of
66
income tax expense. The Company hasWe have concluded that there are no material uncertain tax positions and hashave not recorded an income tax expense or liability for uncertain tax positions as of December 31, 2018.2020.
On December 22, 2017, the “TaxTax Cuts and Jobs Act”Act of 2017 (TCJA) was enacted into law, which beginning in 2018, made several changes to U.S. corporate income tax provisions. We have identified changesprovisions including a reduction in the TCJA which will have a material effect on our tax provision and future tax obligations. The TCJA reduced the U.S. corporate rate from a maximum rate of 35% to 21% effective January 1, 2018. The effect of this change was to reduce the potential future tax benefits from our deferred tax assets by $19.6 million that we had as of December 31, 2017. We have deferred income taxes as of December 31, 2017 from deferred revenue and net operating loss carryforwards and the reduction in the U.S. rate reduced the future value of these assets. The TCJA also changed the potential benefit ofallowed net operating losses incurred after January 1, 2018. The new law eliminated the ability2018 to carryback net operating losses to prior years and also limited the amount of net operating losses incurred post January 1, 2018 that could be used to offset taxable income to 80% of the taxable income generated in any one year.carried forward indefinitely.
The other material change in our tax provision from the TCJA is elimination of the U.S. corporate alternative minimum tax (AMT) system and allowance for a tax refund for AMT credit carryovers as of December 31, 2017.2017, which do not expire. We recorded an incomereceived a tax receivablerefund of $0.8 million in each of 2019 and 2020 related to federal AMT credit carryovers of $1.6 million as of December 31, 2018.carryovers.
We recorded net deferred tax assets of $82.5$106.0 million as of December 31, 2018,2020, which was fully offset by a valuation allowance due to uncertainties surrounding our ability to realize these tax benefits. The deferred tax assets are primarily comprised of deferred revenue, federal and state tax net operating loss (NOL) carryforwards and research and development tax credit carryforwards. As of December 31, 2018,2020, we had cumulative net operating loss carryforwards for federal income tax purposes of approximately $191.2$213.6 million; $102.6$68.0 million of such losses were incurred prior to December 31, 2017 and $88.6$145.6 million were incurred in the yearyears ending on or after December 31, 2018. We also had available tax credit carryforwards of $14.9$26.7 million for federal tax purposes. We had cumulative state tax loss carryforwards at December 31, 20182020 of $138.9$161.4 million, and available state tax credit carryforwards of approximately $8.2$14.3 million, which can be carried forward to offset future taxable income, if any.
Our federal net operating loss carryforwards incurred prior to January 1, 2018 expire starting in 2026,2026; state net operating lossesloss carryforwards expire starting in 2031,2035; and federal tax credit carryforwards begin to expire starting in 2019. Upon analysis, we believe that our net operating losses and2020. Approximately $0.3 million of federal tax credits were subject to an annual limitation due to the ownership change provisions by the Internal Revenue Code of 1986 under Section 382 and similar state provisions. As a result of the limitations under Section 382, our federal and state tax operating loss and tax credit carryforwards have been limited.will expire if unused from 2020 through 2024.
No income tax expense or benefit was recorded for the year ended December 31, 2018.2020. We recorded a net benefitan income tax expense of $0.5$0.3 million related to federal and state AMTs,AMT for the year ended December 31, 2017,2019, and we recorded ano income tax expense of $1.0 million, related to federal and state AMTsor benefit was recorded for the year ended December 31, 2016. 2018.
70
Valuation of Stock‑BasedStock-Based Compensation
We record the fair value of stock options and shares issued under our Employee Stock Purchase Plan (ESPP) to employees as of the grant date as compensation expense over the service period, which is generally the vesting period. For non‑employees,non-employees, we also record the fair value of stock options as of the grant date as compensation expense over the service period. We then periodically re‑measurere-measure the awards to reflect the current fair value at each reporting period until the non‑employeenon-employee completes the performance obligation or the date on which a performance commitment is reached. Expense is recognized over the related service period.
We calculate the fair value of stock‑basedstock-based compensation awards using the Black‑Scholes option‑pricingBlack-Scholes option-pricing model. The Black‑Scholes option‑pricingBlack-Scholes option-pricing model requires the use of subjective assumptions, including volatility of our common stock, the expected term of our stock options, the risk freerisk-free interest rate for a period that approximates the expected term of our stock options and the fair value of the underlying common stock on the date of grant.
Common Stock Options Fair Value
We recognize stock‑basedstock-based compensation expense in accordance with the provisions of ASC Topic 718, Compensation—Stock Compensation. The use of a Black‑ScholesBlack-Scholes model requires us to apply judgment and make assumptions and estimates that include the following:
| Expected Volatility—Volatility is a measure of the amount by which a financial variable such as a share price has fluctuated (historical volatility) or is expected to fluctuate (expected volatility) during a period. |
67
| Expected Dividend Yield—We have never declared or paid dividends and have no plans to do so in the foreseeable future. |
|
|
| Expected Term—This is the period of time that the options granted are expected to remain unexercised. Options granted have a maximum term of ten years and we have estimated the expected life of the option term to be between |
Results of Operations
Comparison of the YearYears Ended December 31, 20182020 and 20172019
The following table summarizes our results of operations for the years ended December 31, 20182020 and 20172019 (in millions):
| | | | | | | | | | |
| | Year ended |
| |||||||
| | December 31, |
| |||||||
| | 2020 | | 2019 | | Change |
| |||
Revenues: |
| |
|
| |
|
| |
|
|
Research collaboration | | $ | 4.5 | | $ | 16.3 | | $ | (11.8) | |
Milestone | |
| 50.2 | |
| 23.2 | |
| 27.0 | |
Licensing | |
| 50.2 | |
| 112.2 | |
| (62.0) | |
Royalties | |
| 17.8 | |
| 5.0 | |
| 12.8 | |
Total revenues | |
| 122.7 | |
| 156.7 | |
| (34.0) | |
Operating expenses: | | | | | | | | | | |
Research and development | | | 169.8 | |
| 118.6 | | | 51.2 | |
General and administrative | | | 29.7 | |
| 24.3 | | | 5.4 | |
Total operating expenses | | | 199.5 | |
| 142.9 | | | 56.6 | |
Other income, net | | | 7.5 | |
| 13.4 | | | (5.9) | |
Income tax expense | | | — | | | 0.3 | | | (0.3) | |
Net income (loss) | | $ | (69.3) | | $ | 26.9 | | $ | (96.2) | |
71
|
|
|
|
|
|
|
|
|
|
|
|
| Year ended |
| |||||||
|
| December 31, |
| |||||||
|
| 2018 |
| 2017 |
| Change |
| |||
|
|
|
|
| (As Revised) |
|
|
|
| |
Revenues: |
|
|
|
|
|
|
|
|
|
|
Research collaboration |
| $ | 20.1 |
| $ | 20.1 |
| $ | 0.0 |
|
Milestone |
|
| 20.5 |
|
| 26.0 |
|
| (5.5) |
|
Licensing |
|
| — |
|
| 0.1 |
|
| (0.1) |
|
Total revenues |
|
| 40.6 |
|
| 46.2 |
|
| (5.6) |
|
Operating expenses: |
|
|
|
|
|
|
|
|
|
|
Research and development |
|
| 97.5 |
|
| 71.8 |
|
| 25.7 |
|
General and administrative |
|
| 22.5 |
|
| 17.5 |
|
| 5.0 |
|
Total operating expenses |
|
| 120.0 |
|
| 89.3 |
|
| 30.7 |
|
Other income, net |
|
| 9.0 |
|
| 4.2 |
|
| 4.8 |
|
Income tax benefit |
|
| — |
|
| (0.5) |
|
| 0.5 |
|
Net loss |
| $ | (70.4) |
| $ | (38.5) |
| $ | (32.0) |
|
Revenues
Research collaboration revenues in 20182020 and 20172019 represent revenue recognized under our Novartis Agreement.Genentech and Astellas agreements.
Milestone and contingent payments decreasedincreased by $5.5$27.0 million in 20182020 over 20172019 amounts primarily due to receiving contractual milestones in 2017 from Amgen, CSLAlexion, Astellas, and MorphoSys in 2020 compared to contractual milestones received from Amgen, Alexion, and Novartis in 2018. 2019.
Licensing revenues in 2020 primarily consist of revenues recognized from various technology and product license agreements entered throughout the year, and licensing revenues in 2019 primarily consist of revenues recognized from our Genentech agreement.
Royalty revenues for 2020 represent revenue recognized from our Alexion and MorphoSys agreements while royalty revenues in 2019 represent royalties from our Alexion agreement.
68
Research and Development Expenses
The following table summarizes our research and development expenses for the years ended December 31, 20182020 and 20172019 (in millions):
|
|
|
|
|
|
|
|
|
|
|
|
| Year Ended |
| |||||||
|
| December 31, |
| |||||||
|
| 2018 |
| 2017 |
| Change |
| |||
Product programs: |
|
|
|
|
|
|
|
|
|
|
XmAb5871 programs |
| $ | 23.0 |
| $ | 20.3 |
| $ | 2.7 |
|
XmAb7195 program |
|
| 0.8 |
|
| 3.4 |
|
| (2.6) |
|
Bispecific programs: |
|
|
|
|
|
|
|
|
|
|
CD-3 |
|
| 23.1 |
|
| 21.3 |
|
| 1.8 |
|
TME checkpoints |
|
| 33.1 |
|
| 20.7 |
|
| 12.4 |
|
Cytokines |
|
| 7.7 |
|
| — |
|
| 7.7 |
|
Subtotal Bispecific programs |
|
| 63.9 |
|
| 42.0 |
|
| 21.9 |
|
Other, research and early stage programs |
|
| 9.8 |
|
| 6.1 |
|
| 3.7 |
|
Total research and development expense |
| $ | 97.5 |
| $ | 71.8 |
| $ | 25.7 |
|
| | | | | | | | | | |
| | Year Ended |
| |||||||
| | December 31, |
| |||||||
| | 2020 | | 2019 | | Change |
| |||
Product programs: | | | | | | | | | | |
Obexelimab (XmAb5871) |
| $ | 2.9 | | $ | 17.5 | | $ | (14.6) | |
| | | | | | | | | | |
Bispecific programs: | | | | | | | | | | |
CD3 programs: | | | | | | | | | | |
Vibecotamab* | | | 12.4 | | | 11.6 | | | 0.8 | |
Plamotamab | | | 33.8 | | | 12.3 | | | 21.5 | |
Tidutamab | | | 14.9 | | | 11.4 | | | 3.5 | |
XmAb819 (ENPP3 x CD3) | | | 7.4 | | | 0.5 | | | 6.9 | |
Total CD3 programs | | | 68.5 | | | 35.8 | | | 32.7 | |
| | | | | | | | | | |
Tumor microenvironment (TME) activator programs: | | | | | | | | | | |
XmAb717 | | | 26.4 | | | 13.0 | | | 13.4 | |
XmAb104 | | | 13.3 | | | 7.8 | | | 5.5 | |
XmAb841 | | | 10.6 | | | 7.4 | | | 3.2 | |
Total TME activator programs | | | 50.3 | | | 28.2 | | | 22.1 | |
| | | | | | | | | | |
Cytokine programs: | | | | | | | | | | |
XmAb306/RG6323* | | | 12.0 | | | 17.0 | | | (5.0) | |
XmAb564 | | | 15.4 | | | 5.0 | | | 10.4 | |
Total cytokine programs | | | 27.4 | | | 22.0 | | | 5.4 | |
| | | | | | | | | | |
Subtotal bispecific programs | | | 146.2 | | | 86.0 | | | 60.2 | |
| | | | | | | | | | |
Other, research and early stage programs | | | 20.7 | | | 15.1 | |
| 5.6 | |
| | | | | | | | | | |
Total research and development expenses |
| $ | 169.8 | | $ | 118.6 | | $ | 51.2 | |
*Includes net reimbursements from our partners pursuant to agreements that include cost-sharing arrangements.
Research and development expenses increased by $25.7$51.2 million in 20182020 over 20172019 amounts as we continue to expand our pipeline of bispecific Fc domainantibody and cytokine candidates. Increased research and development spending in 2020 was driven by increased spending on our bispecific TME checkpoint candidatesplamotamab, XmAb819, XmAb717 and our IL-15 cytokine program was the primary driver for increased spending. Increased spending on our XmAb5871 programXmAb564 programs and early discovery research programs was partially offset by reducedlower spending on our XmAb7195 program.obexelimab program during the year.
General and Administrative Expenses
General and administrative expenses increased by $5.0$5.4 million in 2020 over 2019 amounts primarily due to an increase in staffing, professional expenses and spending on intellectual property and licenses.
Other Income, Net
Other income, net decreased by $5.9 million in 2020 over 2019 amounts reflecting decreases in interest income earned on our investments in marketable securities, due to declining in interest rates in 2020.
69
Comparison of the Years Ended December 31, 2019 and 2018
The following table summarizes our results of operations for the year ended December 31, 2019 and 2018 (in millions):
| | | | | | | | | | |
| | Year Ended |
| |||||||
| | December 31, |
| |||||||
| | 2019 | | 2018 | | Change |
| |||
Revenues: |
| |
|
| |
|
| |
| |
Research collaboration | | $ | 16.3 | | $ | 20.1 | | $ | (3.8) | |
Milestone | |
| 23.2 | |
| 20.5 | |
| 2.7 | |
Licensing | |
| 112.2 | |
| — | |
| 112.2 | |
Royalties | | | 5.0 | | | — | | | 5.0 | |
Total revenues | |
| 156.7 | |
| 40.6 | |
| 116.1 | |
Operating expenses: | | | | | | | | | | |
Research and development | |
| 118.6 | |
| 97.5 | | | 21.1 | |
General and administrative | |
| 24.3 | |
| 22.5 | | | 1.8 | |
Total operating expenses | |
| 142.9 | |
| 120.0 | | | 22.9 | |
Other income, net | |
| 13.4 | |
| 9.0 | | | 4.4 | |
Income tax benefit | | | 0.3 | | | — | | | 0.3 | |
Net income (loss) | | $ | 26.9 | | $ | (70.4) | | $ | 97.3 | |
Revenues
Research collaboration revenues in 2019 represent revenue recognized under our Genentech and Astellas agreements while the research collaboration revenues in 2018 represent revenue recognized under our Novartis Agreement.
Milestone payments increased by $2.7 million in 2019 over 20172018 amounts primarily due to receiving contractual milestones in 2019 from Amgen, Alexion and Novartis compared to contractual milestones received primarily from Alexion in 2018.
Licensing revenues in 2019 primarily consist of revenues recognized from our Genentech agreement.
Royalty revenues for 2019 represent royalty revenue recognized from our Alexion agreement.
70
Research and Development Expenses
The following table summarizes our research and development expenses for the years ended December 31, 2019 and 2018 (in millions):
| | | | | | | | | |
| | Year Ended | |||||||
| | December 31, | |||||||
| | 2019 | | 2018 | | Change | |||
Product programs: |
| | | | | | | | |
Obexelimab (XmAb5871) | | $ | 17.5 | | $ | 23.0 | | $ | (5.5) |
| | | | | | | | | |
Bispecific programs: | | | | | | | | | |
CD3 programs: | | | | | | | | | |
Vibecotamab* | | | 11.6 | | | 9.3 | | | 2.3 |
Plamotamab | | | 12.3 | | | 5.6 | | | 6.7 |
Tidutamab | | | 11.4 | | | 7.8 | | | 3.6 |
XmAb819 (ENPP3 x CD3) | | | 0.5 | | | — | | | 0.5 |
Total CD3 programs | | | 35.8 | | | 22.7 | | | 13.1 |
| | | | | | | | | |
Tumor microenvironment (TME) activator programs: | | | | | | | | | |
XmAb717 | | | 13.0 | | | 8.7 | | | 4.3 |
XmAb104 | | | 7.8 | | | 14.5 | | | (6.7) |
XmAb841 | | | 7.4 | | | 9.9 | | | (2.5) |
Total TME activator programs | | | 28.2 | | | 33.1 | | | (4.9) |
| | | | | | | | | |
Cytokine programs: | | | | | | | | | |
XmAb306/RG6323* | | | 17.0 | | | 7.7 | | | 9.3 |
XmAb564 | | | 5.0 | | | — | | | 5.0 |
Total cytokine programs | | | 22.0 | | | 7.7 | | | 14.3 |
| | | | | | | | | |
Subtotal bispecific programs | | | 86.0 | | | 63.5 | | | 22.5 |
| | | | | | | | | |
Other, research and early stage programs | | | 15.1 | | | 11.0 | |
| 4.1 |
| | | | | | | | | |
Total research and development expenses | | $ | 118.6 | | $ | 97.5 | | $ | 21.1 |
*Includes net payments from our partners pursuant to agreements that include cost-sharing arrangements.
Research and development expenses increased by $21.1 million in 2019 over 2018 amounts as we continue to expand our pipeline of bispecific antibody and cytokine candidates. Increased spending on our CD3 bispecific and our cytokine programs offset reduced spending on our TME activator candidates during the year.
General and Administrative Expenses
General and administrative expenses increased by $1.8 million in 2019 over 2018 amounts primarily due to an increase in facility costs, staffing and stock-based compensationintellectual property costs.
7271
Other Income, (Expense), Net
Other income, net increased by $4.8$4.4 million in 20182019 over 20172018 amounts reflecting additional interest income earned on our investments in marketable securities, which is due to higher investment balances as a result of our March 2018 financing.
Comparison of the Year Ended December 31, 2017 and 2016
The following table summarizes our results of operations for the year ended December 31, 2017 and 2016 (in millions):
|
|
|
|
|
|
|
|
|
|
|
|
| Year Ended |
| |||||||
|
| December 31, |
| |||||||
|
| 2017 |
| 2016 |
| Change |
| |||
|
| (As Revised) |
| (As Revised) |
|
|
|
| ||
Revenues: |
|
|
|
|
|
|
|
|
|
|
Research collaboration |
| $ | 20.1 |
| $ | 34.2 |
| $ | (14.1) |
|
Milestone |
|
| 26.0 |
|
| 5.0 |
|
| 21.0 |
|
Licensing |
|
| 0.1 |
|
| 69.8 |
|
| (69.7) |
|
Total revenues |
|
| 46.2 |
|
| 109.0 |
|
| (62.8) |
|
Operating expenses: |
|
|
|
|
|
|
|
|
|
|
Research and development |
|
| 71.8 |
|
| 51.9 |
|
| 19.9 |
|
General and administrative |
|
| 17.5 |
|
| 13.1 |
|
| 4.4 |
|
Total operating expenses |
|
| 89.3 |
|
| 65.0 |
|
| 24.3 |
|
Other income, net |
|
| 4.2 |
|
| 2.1 |
|
| 2.1 |
|
Income tax expense (benefit) |
|
| (0.5) |
|
| 1.0 |
|
| (1.5) |
|
Net income (loss) |
| $ | (38.4) |
| $ | 45.1 |
| $ | (83.5) |
|
Revenues
Research collaboration revenues decreased by $14.2 million in 2017 over 2016 amounts primarily due to revenue recognized under our Novartis collaboration in 2017 compared to revenue recognized under our Novartis and Amgen collaborations in 2016.
Milestone and contingent payments increased by $21.0 million in 2017 over 2016 amounts primarily due to receiving contractual milestones in 2017 from Amgen, CSL, and MorphoSys, compared to contractual milestonesupfront proceeds received from Alexionour Genentech and Astellas agreements in 2016.March 2019.
Licensing revenue decreased by $69.7 million in 2017 over 2016 amounts due to revenue reported under our Novartis collaboration in 2016.
73
Research and Development Expenses
The following table summarizes our research and development expenses for the years ended December 31, 2017 and 2016 (in millions):
|
|
|
|
|
|
|
|
|
|
|
| Year Ended | |||||||
|
| December 31, | |||||||
|
| 2017 |
| 2016 |
| Change | |||
Product programs: |
|
|
|
|
|
|
|
|
|
XmAb5871 programs |
| $ | 20.3 |
| $ | 17.3 |
| $ | 3.0 |
XmAb7195 program |
|
| 3.4 |
|
| 7.5 |
|
| (4.1) |
Bispecific programs: |
|
|
|
|
|
|
|
|
|
CD-3 |
|
| 21.3 |
|
| 17.9 |
|
| 3.4 |
TME checkpoints |
|
| 20.7 |
|
| 5.8 |
|
| 14.9 |
Cytokines |
|
| — |
|
| — |
|
| — |
Subtotal Bispecific programs |
|
| 42.0 |
|
| 23.7 |
|
| 18.3 |
Other, research and early stage programs |
|
| 6.1 |
|
| 3.4 |
|
| 2.7 |
Total research and development expense |
| $ | 71.8 |
| $ | 51.9 |
| $ | 19.9 |
Research and development expenses increased by $19.9 million in 2017 over 2016 amounts as we continue to expand our pipeline of bispecific candidates. The primary increases in research and development spending were on our bispecific TME checkpoint and CD-3 programs. Increased spending on our XmAb5871 program and early discovery research programs was partially offset by reduced spending on our XmAb7195 program.
General and Administrative Expenses
General and administrative expenses increased by $4.4 million in 2017 over 2016 amounts primarily due to an increase in facility costs, staffing and stock-based compensation costs.
Other Income (Expense), Net
Other income, net increased by $2.1 million in 2017 over 2016 amounts, reflecting additional interest income earned on our investments in marketable securities.
Liquidity and Capital Resources
Since our inception, our operations have been primarily financed through proceeds from our public offering, private sales of our equity, convertible notes and payments received under our collaboration and development partnerships and licensing arrangements. We have devoted our resources to funding research and development programs, including discovery research, preclinical and clinical development activities.
We have incurred substantial operating losses since our inception, and we expect to continue to incur operating losses into the foreseeable future as we advance the ongoing development of our bispecific Fc domain pipeline ofantibody and cytokine product candidates, XmAb14045, XmAb13676, XmAb18087, XmAb20717, XmAb22841, XmAb23104, and XmAb24306, evaluate opportunities for the potential clinical development of our other preclinical programs, and continue our research efforts.
In 2020, we received a total of $165 million in upfront payments, milestones and royalties in connection with licensing of our technologies and products.
In March 2019, we received a total of $135.0 million in upfront payment in connection with our Genentech and Astellas collaboration agreements.
In March 2018, we finalizedcompleted the sale of 8,395,000 shares of common stock at an offering pricewhich included shares that we issued pursuant the underwriters’ exercise of $31.00 per share in an underwritten offering, resulting intheir over-allotment option pursuant to a follow-on public offering. We received net proceeds of approximately $245.5 million, after deducting underwriters’ commissions and offering expenses.
74
In July 2016 we received a $150.0 million upfront payment in connection with our collaboration with Novartis. On December 6, 2016, we finalized the sale of 5,272,750 shares of common stock at an offering price of $24.00 per share in an underwritten offering, resulting in net proceeds of approximately $119.3 million, after deducting underwriting discounts commissions and offering expenses.
On September 19, 2016, we entered into an Equity Distribution Agreement (the Distribution Agreement) with Piper Jaffray & Co (Piper Jaffray) pursuant to which we may sell from time to time, at our option, up to an aggregate of $40 million of common stock through Piper Jaffray as sales agent. The issuance and sale of these shares by Xencor under the Distribution Agreement will be pursuant to our shelf registration statement on Form S-3 (File No.333-213700) declared effective by the SEC on October 5, 2016.
To date, we have not sold any shares under the Distribution Agreement.
At December 31, 2018,2020, we had $530.5$604.0 million of cash, cash equivalents and marketable debt securities compared to $363.3$601.3 million at December 31, 2017.2019. We expect to continue to receive additional payments from our collaborators for research and development services rendered, additional milestone, contingent payments, opt-in and annual license maintenanceroyalty payments. We expect to close the Genentech transaction in the first quarter of 2019, for which we will receive a $120 million non-refundable upfront payment 30 days after the effective date. Our ability to receive milestone payments and contingent payments from our partners is dependent upon either our ability or our partners’ abilities to achieve certain levels of research and development activities and is therefore uncertain at this time.
Funding Requirements
We have not generated any revenue from product sales and do not expect to do so until we obtain regulatory approval and commercialize one or more of our product candidates. As we are currently in the early clinical stages of development, it will be some time before we expect to achieve this, and it is uncertain that we ever will. We expect that our operating expenses will continue to increase in connection with ongoing as well as additional planned clinical and preclinical development of product candidates in our pipeline. We expect to continue our collaboration arrangements and will look for additional collaboration and licensing opportunities.
Although it is difficult to predict our funding requirements, based upon our current operating plan, we expectbelieve that our existing cash, cash equivalents and marketable securities, together with interest thereon and certain potentialexpected milestone and royalty payments will be sufficient to fund our operating expenses and capital expenditure requirements beyondoperations into 2024. We have based these estimates on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently expect.
72
Cash Flows
The following table sets forth the primary sources and uses of cash and cash equivalents for each of the periods presented below (in thousands):
|
|
|
|
|
|
|
|
|
|
| ||||||||||
|
| Year Ended December 31, |
| |||||||||||||||||
|
| 2018 |
| 2017 |
| 2016 |
| |||||||||||||
|
|
|
|
| (As Revised) |
| (As Revised) |
| ||||||||||||
| | | | | | | | | | | ||||||||||
| | Year Ended December 31, |
| |||||||||||||||||
| | 2020 | | 2019 | | 2018 |
| |||||||||||||
Net cash provided by (used in): |
|
|
|
|
|
|
|
|
|
|
| |
|
| |
|
| |
| |
Operating activities |
| $ | (79,756) |
| $ | (33,597) |
| $ | 95,238 |
| | $ | (5,004) | | $ | 64,374 | | $ | (79,756) | |
Investing activities |
|
| (164,767) |
|
| 31,864 |
|
| (214,274) |
| |
| 100,192 | |
| (50,970) | |
| (164,767) | |
Financing activities |
|
| 254,241 |
|
| 3,733 |
|
| 120,974 |
| | | 18,044 | |
| 10,662 | |
| 254,241 | |
Net increase in cash and cash equivalents |
| $ | 9,718 |
| $ | 2,000 |
| $ | 1,938 |
| | $ | 113,232 | | $ | 24,066 | | $ | 9,718 | |
Operating Activities
Net cash used inby operating activities for the year ended December 31, 20182020 reflects that upfront and December 31, 2017, reflectsmilestone payments and royalties received in the year funded a majority of the operating expenses primarily for advancing our bispecific candidates and clinical trials for XmAb5871incurred during the year.
75
Net cash provided by operating activities for the year ended December 31, 20162019 reflects the upfront payment of $150.0 millionand milestone payments received under our Novartis collaboration and a milestone payment from Alexion in excess of operating expenses, while net cash used in operations for the years ended December 31, 2018 reflects operating expenses in excess of milestone payments primarily for advancing our pipeline of bispecific antibody candidates during the year.such years.
Investing Activities
Investing activities consist primarily of proceeds from maturities of marketable securities offset by purchases of marketable securities available-for-sale, acquisition of intangible assets and purchases of property and equipment. In 2020, we redeemed $114.0 million of marketable securities, net of $643.7 million of purchase. In 2019, we purchased $39.9 million of marketable securities, net of $456.9 million of proceeds from sales and maturities. In 2018, we purchased $155.7 million in marketable securities, net of $222.1 million of proceeds from sale and maturities. In 2017 we received $39.2 million in marketable securities, net of $76.5 million of purchases. In 2016, we invested $210.6 million in marketable securities net of $105.5 million of sales and maturities. We acquired $1.9$3.2 million, $2.0$3.7 million and $1.5$1.9 million of intangible assets in the years ended December 31, 2018, 20172020, 2019 and 2016,2018, respectively. We purchased $7.2$10.5 million, $5.3$7.4 million and $1.5$7.2 million of capital equipment for the years ended December 31, 2018, 20172020, 2019 and 20162018 respectively. The increase in capital expenditure in 20182020 compared to 20172019 and 20162018 is primarily due to additional purchasefacility improvements for our laboratory facilities.
Financing Activities
Net cash provided by financing activities during the year ended December 31, 2020 and 2019 consists primarily of researchcash from stock option exercises and development equipment.
Financing Activitiesthe sales of shares under the ESPP.
Net cash provided by financing activities during the year ended December 31, 2018 consists primarily of net proceeds from theour March 2018 follow-on equitypublic offering and cash from stock option exercises and the sale of shares under the ESPP.
Net cash provided by financing activities during the year ended December 31, 2017 consists primarily of cash from stock option exercises and the sale of shares under the ESPP.
Net cash provided by financing activities during the year ended December 31, 2016 consists primarily of net proceeds from the follow-on equity offering and cash from stock option exercises and the sale of shares under the ESPP.
Contractual Obligations and Commitments
The following table summarizes our contractual obligations at December 31, 20182020 (in thousands):
| | | | | | | | | | | | | | | | |
| | Payments due by period |
| |||||||||||||
| | | | | Less | | | | | | | | More |
| ||
| | | | | than | | 1 - 3 | | 3 - 5 | | than |
| ||||
| | Total | | 1 year | | Years | | Years | | 5 years |
| |||||
Operating lease obligation relating to facilities (1) |
| $ | 6,645 |
| $ | 2,428 |
| $ | 2,800 |
| $ | 1,417 |
| $ | — | |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Payments due by period |
| |||||||||||||
|
|
|
|
| Less |
|
|
|
|
|
|
| More |
| ||
|
|
|
|
| than |
| 1 - 3 |
| 3 - 5 |
| than |
| ||||
|
| Total |
| 1 year |
| Years |
| Years |
| 5 years |
| |||||
Operating lease obligation relating to facilities (1) |
| $ | 8,542 |
| $ | 2,752 |
| $ | 5,790 |
| $ | — |
| $ | — |
|
| (1) |
| Consists of operating leases on our corporate headquarters in Monrovia, CA encompassing two floors of 24,000 square feet each |
73
| that expire in December 2025 and September 2022, respectively, and on our San Diego, CA offices encompassing |
We are obligated to make future payments to third parties under in‑licensein-license agreements, including sublicense fees, royalties, and payments that become due and payable on the achievement of certain development and commercialization milestones. We have also entered into agreements with third party vendors which will require us to make future payments upon the delivery of goods and services in future periods.
In February 2015, we entered into a license agreement with BIO-TECHNE Corporation (BIO-TECHNE) for a non-exclusive license to certain antibody technology including monoclonal antibodies which recognize human somatostatin reception 2.receptor 2 (SSTR2). The variable domain of this antibody is incorporated in our XmAb18087tidutamab drug candidate. Under this license agreement, we may be required to make $3.8 million in additional contingent payments which include $800,000 of clinical milestones and $3.0 million of regulatory milestones, in addition to royalties upon commercial sales of products of less than 1%. We made an upfront payment of $200,000 in connection with this license and made a Phase 1 milestone payment of $100,000 in 2018. We didhave not makemade any additional milestone payments in 2017 or 2016.under this arrangement.
76
In January 2019, weWe entered into a second agreement with BIO-TECHNE, which agreement is effective February 2018, for a non-exclusive license to a certain recombinant monoclonal antibody reactive with human programmed death protein, PD-1 antibody. We expect to use this protein in certain of our oncology drug candidates.PD-1. Under this license agreement, we may be required to make $22.0 million in additional contingent payments which include $1.5 million of clinical milestones, $4.5 million of regulatory milestones and milestones on the achievement of certain sales of $16.0 million, in addition to royalties upon commercial sales of products of 1%. We made an upfront payment in connection with this license in 2019 and didhave not makemade any additional payments in 2018, 2017 or 2016under this license agreement.
In November 2015, we entered into a worldwide exclusive commercial license agreement with Selexis SA to develop and commercialize products produced from the Selexis cell line that was manufactured in connection with our XmAb14045vibecotamab drug candidate. We made an upfront payment of 50,000 Swiss Francs (CHF) in connection with the license and may be required to make CHF 1.7 million in additional contingent obligations which include CHF 500,000 in development milestones, CHF 400,000 in regulatory milestones and CHF 800,000 in sales milestones, in addition to royalties upon commercial sales of products of less than 1%. During 2016, we made a CHF 100,000 milestone payment in connection with an IND filing.submission. There were no additional milestone payments made in 2018 or 2017.under this license agreement.
In February 2016, we entered into a worldwide exclusive commercial license agreement with Selexis SA to develop and commercialize products produced from the Selexis cell line that was manufactured in connection with our XmAb13676plamotamab drug candidate. In connection with the license, we may be required to make CHF 1.7 million in additional contingent obligations which include CHF 500,000 in development milestones, CHF 400,000 in regulatory milestones and CHF 800,000 in sales milestones, in addition to royalties upon commercial sales of products of less than 1%. During 2016, we made a CHF 100,000 milestone payment in connection with an IND filing.submission. There were no additional milestone payments made in 2018 or 2017.under this license agreement.
In December 2017, we entered into worldwide exclusive commercial license agreements with Selexis to develop and commercialize products produced from the Selexis cell line that was manufactured for each of our bispecific antibody and cytokine drug candidates: XmAb18087, XmAb20717, XmAb22841tidutamab, XmAb717, XmAb841, XmAb104, XmAb306, XmAb564 and XmAb23104.XmAb819. The terms for each agreement isare identical and for each licensed cell line we may be required to make up to CHF 1.4 million in total development, regulatory and sales milestones which include CHF 425,000 in development milestones, CHF 340,000 in regulatory milestones and CHF 680,000 in sales milestones. In addition, we may be obligated to pay royalties upon commercial sales of approved products of less than 1%. In 2017, we made a CHF 85,000 milestone payment in connection with an IND filing. In 2018, we made three milestone payments of CHF 85,000 each in connection with three separate IND filings.
submissions. In December 2015,2019, we entered intomade a Cell Line Sale Agreement with Catalent Pharma Solutions LLC for a worldwide license to develop and commercialize products produced from the Catalent cell line that was manufacturedmilestone payment of CHF 75,000 in connection with our XmAb5871 drug candidate. Under the termsan IND submission, and in 2020, we recorded a milestone payment due of the agreement, we may be obligated to make contingent payments upon transfer of the XmAb5871 manufacturing process to a third party. These contingent payments total $2.75 million and include $500,000 in development milestones and $2.25 million in regulatory milestones in addition to royalties on net sales of XmAb5871 approved products with such royalties less than 1%. In 2017 we transferred the manufacturing process for XmAb5871 to a third-party manufacturer. We did not make any milestone payments under this Agreement in 2018 and 2017.
In December 2011, we entered into a Cell Line Sale Agreement with Catalent Pharma Solutions LLC for a worldwide license to develop and commercialize products produced from the Catalent cell line that was manufacturedCHF 75,000 in connection with our XmAb7195 drug candidate. This agreement was subsequently amended in April 2015. Under the terms of the agreement, we may be obligated to make contingent payments upon transfer of the XmAb7195 manufacturing process to a third party. These contingent payments total $2.75 million and include $500,000 in development milestones and $2.25 million in regulatory milestones in addition to royalties on net sales of XmAb7195 approved products with such royalties less than 1%. We did not make any milestone payments under this Agreement in 2018 and 2017.
77
an IND submission.
In December 2012, we entered into a Cross-License Agreement with MedImmune, LLC (MedImmune) for a non-exclusive license to certain MedImmune patents related to half-life technology. Under the terms of the agreement, we may be obligated to make contingent payments in connection with the use of our Xtend™ technology, including use
74
by us in our development candidates and also for use by our licensees. These contingent payments total $250,000 per program and include $150,000 in clinical milestones and $100,000 in regulatory milestones. In addition, we may be obligated to make contingent payments for tiered sales milestones on the sale of approved products from $20,000 per year to $1.0 million per year. Our obligations to make payments under this agreement expire in December 2021. We made milestone payments under this agreement of $125,000, $75,000 and $125,000$375,000 for 20162018, 2019 and 2018,2020, respectively.
As the amount and timing of sublicense fees and the achievement and timing of these milestones are not probable and estimable, such commitments have not been included on our balance sheet or in the contractual obligations and commitment tables above.
Off‑BalanceOff-Balance Sheet Arrangements
We did not have during the periods presented, and we do not currently have, any off‑balanceoff-balance sheet arrangements.
New Accounting Pronouncements
See Note 1 - Recent Accounting Pronouncementsin the accompanying financial statements for information regarding recent accounting pronouncements.
Item 7A.7A. Quantitative and Qualitative Disclosures About Market Risk
Our primary exposure to market risk is interest income sensitivity, which is affected by changes in the general level of U.S. interest rates. Due to the short‑termshort-term duration of our investment portfolio and the low risk profile of our investments, an immediate 10.0% change in interest rates would not have a material effect on the fair market value of our portfolio. Accordingly, we would not expect our operating results or cash flows to be affected to any significant degree by the effect of a sudden change in market interest rates on our investment portfolio.
We do not believe that our cash, and cash equivalents and marketable securities have significant risk of default or illiquidity. While we believe our cash, and cash equivalents and marketable securities do not contain excessive risk, we cannot provide absolute assurance that in the future our investments will not be subject to adverse changes in market value. In addition, we maintain significant amounts of cash and cash equivalents at one or more financial institutions that are in excess of federally insured limits.
Inflation generally affects us by increasing our cost of labor and clinical trial costs. We do not believe that inflation has had a material effect on our results of operations during the periods presented.
Xencor, Inc.
Financial Statements
Audited Financial Statements for the Years Ended December 31, |
| |
| 76 | |
| 79 | |
| 80 | |
| 81 | |
| 82 | |
| 83 |
7875
Report of Independent Registered Public Accounting Firm
To the Stockholders and the Board of Directors and Stockholdersof
Xencor, Inc.
Opinion on the Financial Statements
We have audited the accompanying balance sheets of Xencor, Inc. (the Company) as of December 31, 20182020 and 2017,2019, the related statements of comprehensive income (loss), stockholders’ equity and cash flows for each of the three years in the period ended December 31, 2018,2020, and the related notes to the financial statements. In our opinion, the financial statements present fairly, in all material respects, the financial position of the Company as of December 31, 20182020 and 2017,2019, and the results of its operations and its cash flows for each of the three years in the period ended December 31, 2018,2020, in conformity with accounting principles generally accepted in the United States of America.
We have also audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the Company’s internal control over financial reporting as of December 31, 2018,2020, based on criteria established in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission in 2013, and our report, dated February 25, 2019,23, 2021, expressed an unqualified opinion on the effectiveness of the Company’s internal control over financial reporting.
Change in Accounting Principle
As discussed in Note 1 to the financial statements, the Company has changed its method of accounting for revenue recognition in fiscal years 2018 and 2017 due to the adtoption of Accounting Standards Condification, Topic 606, Revenue from Contracts with Customers.
Basis for Opinion
These financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s financial statements based on our audits. We are a public accounting firm registered with the PCAOB and are required to be independent with respect to the Company in accordance with 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 audits to obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the 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 financial statements. We believe that our audits provide a reasonable basis for our opinion.
Critical Audit Matter
The critical audit matter communicated below is a matter arising from the current-period audit of the financial statements that was communicated or required to be communicated to the audit committee and that: (1) relates to accounts or disclosures that are material to the financial statements; and (2) involved our especially challenging, subjective or complex judgments. The communication of the critical audit matter does not alter in any way our opinion on the financial statements taken as a whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the critical audit matter or on the accounts or disclosures to which it relates.
Revenue Recognition—Collaboration and Licensing Agreements
As discussed in Note 10 to the financial statements, the Company entered into collaboration and licensing agreements during the year ended December 31, 2020. These contracts contain multiple performance obligations. Management’s identification of the performance obligations requires significant judgment, including whether the performance obligations are distinct and capable of being distinct, which requires management to evaluate whether the customer can benefit from the good or service on its own, or together with other resources readily available to the customer. Management applies significant judgment in determining the revenue recognition for these collaboration and licensing contracts including the identification of and accounting for all performance obligations and the calculation of the standalone selling price (SSP) for each identified performance obligation. The Company’s estimate of SSP for each performance obligation within these customer contracts requires management to consider many factors, including
76
external market data as well as an estimate of future profitability. For each performance obligation identified, the Company recognizes revenue upon transfer of control of promised intellectual property and technology licenses or upon delivery of research and development services to its collaboration and licensing partners in an amount that reflects the consideration the Company expects to receive in exchange for those licenses or services.
We identified the Company’s revenue recognition related to the collaboration and licensing agreements as a critical audit matter because auditing the identification and accounting for performance obligations, and the calculation of the SSP for each performance obligation, required significant audit effort and a high degree of auditor judgment and subjectivity to perform our audit procedures and evaluate the audit evidence obtained.
Our audit procedures related to the Company’s collaboration and licensing contracts included the following, among others:
| ● | We obtained and read the collaboration and licensing agreements and evaluated the completeness of the performance obligations identified by management, and performed an evaluation of whether these performance obligations were distinct and capable of being distinct. |
| ● | We obtained an understanding of the relevant controls related to the collaboration and licensing contracts and tested such controls for design, implementation and operating effectiveness, including management review controls related to identifying distinct performance obligations and when transfer of control is satisfied, and determining the SSP over each of the identified performance obligations. |
| ● | We tested management’s process used to estimate the SSP by evaluating the models, including testing the accuracy and completeness of data used, and reasonableness of assumptions applied by management. |
| ● | As each contract has multiple performance obligations, we also tested the allocation of the transaction price to each performance obligation based upon the SSP. |
We have served as the Company’s auditor since 2015.
/s/ RSM US LLP
Los Angeles, California
February 25, 201923, 2021
7977
Report of Independent Registered Public Accounting Firm
Regarding Internal Control Over Financial Reporting
To the Stockholders and the Board of Directors and Stockholdersof
Xencor, Inc.
Opinion on Internal Control Over Financial Reporting
We have audited Xencor, Inc.’s (the Company) internal control over financial reporting as of December 31, 2018,2020, based on criteria established in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission in 2013. In our opinion, the Company maintained, in all material respects, effective internal control over financial reporting as of December 31, 2018,2020, based on criteria established in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission in 2013.
We have also audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the balance sheets of the Company as of December 31, 20182020 and 2017,2019, the related statements of comprehensive income (loss), stockholders’ equity and cash flows for each of the three years in the period ended December 31, 2018,2020, of the Company and our report, dated February 25, 2019,23, 2021, expressed an unqualified opinion.
Basis for Opinion
The Company’s management is responsible for maintaining effective internal control over financial reporting and for its assessment of the effectiveness of internal control over financial reporting in the accompanying Management’s Report on Internal Control Over Financial Reporting. Our responsibility is to express an opinion on the Company’s internal control over financial reporting based on our audit. We are a public accounting firm registered with the PCAOB and are required to be independent with respect to the Company in accordance with U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audit in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether effective internal control over financial reporting was maintained in all material respects. Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, and testing and evaluating the design and operating effectiveness of internal control based on the assessed risk. Our audit also included performing such other procedures as we considered necessary in the circumstances. We believe that our audit provides a reasonable basis for our opinion.
80
Definition and Limitations of Internal Control Over Financial Reporting
A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with accounting principles generally accepted accounting principles.in the United States of America (U.S. GAAP). A company’s internal control over financial reporting includes those policies and procedures that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with generally accepted accounting principles,U.S. GAAP, and that receipts and expenditures of the company are being made only in accordance with authorizations of management and directors of the company; and (3) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use or disposition of the Company’s assets that could have a material effect on the financial statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, 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.
/s/ RSM US LLP
Los Angeles, California
February 25, 201923, 2021
8178
Xencor, Inc.
Balance Sheets
(in thousands, except share and per share data)
| | | | | | | |
| | December 31, |
| ||||
| | 2020 | | 2019 |
| ||
| | | | | | | |
Assets |
| |
|
| |
| |
Current assets | | | | | | | |
Cash and cash equivalents | | $ | 163,544 | | $ | 50,312 | |
Marketable securities | | | 434,156 | |
| 479,470 | |
Equity securities | | | 5,303 | | | — | |
Accounts receivable | | | 11,443 | |
| 21,574 | |
Income tax receivable | | | — | | | 502 | |
Contract asset | | | 12,500 | | | — | |
Prepaid expenses and other current assets | | | 10,726 | |
| 6,547 | |
Total current assets | | | 637,672 | |
| 558,405 | |
Property and equipment, net | | | 21,682 | |
| 15,805 | |
Patents, licenses, and other intangible assets, net | | | 15,977 | |
| 14,421 | |
Marketable securities - long term | | | 1,030 | |
| 71,526 | |
Equity securities - long term | | | 16,071 | | | — | |
Income tax receivable | | | — | | | 402 | |
Right of use asset | | | 10,600 | | | 9,380 | |
Other assets | | | 212 | |
| 311 | |
Total assets | | $ | 703,244 | | $ | 670,250 | |
Liabilities and stockholders’ equity | | | | | | | |
Current liabilities | | | | | | | |
Accounts payable | | $ | 8,954 | | $ | 10,189 | |
Accrued expenses | | | 17,603 | |
| 8,995 | |
Lease liabilities | | | 1,889 | | | 2,169 | |
Deferred revenue | | | 92,615 | | | 45,205 | |
Total current liabilities | | | 121,061 | |
| 66,558 | |
Lease liabilities, net of current portion | | | 9,739 | |
| 8,565 | |
Deferred revenue, net of current portion | | | — | |
| 1,926 | |
Total liabilities | | | 130,800 | |
| 77,049 | |
Commitments and contingencies (see note 9) | | | | | | | |
Stockholders’ equity | | | | | | | |
Preferred stock, $0.01 par value: 10,000,000 authorized shares; -0- issued and outstanding shares at December 31, 2020 and 2019 | | | — | | | — | |
Common stock, $0.01 par value: 200,000,000 authorized shares; 57,873,444 issued and outstanding shares at December 31, 2020 and 56,902,301 issued and outstanding at December 31, 2019 | | | 580 | |
| 569 | |
Additional paid-in capital | | | 937,525 | |
| 887,873 | |
Accumulated other comprehensive income | | | 74 | |
| 1,161 | |
Accumulated deficit | |
| (365,735) | |
| (296,402) | |
Total stockholders’ equity | | | 572,444 | |
| 593,201 | |
Total liabilities and stockholders’ equity | | $ | 703,244 | | $ | 670,250 | |
See accompanying notes to the financial statements.
|
|
|
|
|
|
|
|
|
| December 31, |
| ||||
|
| 2018 |
| 2017 |
| ||
|
|
|
|
| (As Revised) |
| |
Assets |
|
|
|
|
|
|
|
Current assets |
|
|
|
|
|
|
|
Cash and cash equivalents |
| $ | 26,246 |
| $ | 16,528 |
|
Marketable securities |
|
| 268,115 |
|
| 207,603 |
|
Accounts receivable |
|
| 10,187 |
|
| 1,142 |
|
Income tax receivable |
|
| 804 |
|
| — |
|
Prepaid expenses and other current assets |
|
| 10,375 |
|
| 5,606 |
|
Total current assets |
|
| 315,727 |
|
| 230,879 |
|
Property and equipment, net |
|
| 11,813 |
|
| 7,088 |
|
Patents, licenses, and other intangible assets, net |
|
| 11,969 |
|
| 11,148 |
|
Marketable securities - long term |
|
| 236,108 |
|
| 139,198 |
|
Income tax receivable |
|
| 804 |
|
| 1,524 |
|
Loan receivable |
|
| — |
|
| 86 |
|
Interest receivable |
|
| — |
|
| 14 |
|
Other assets |
|
| 311 |
|
| 265 |
|
Total assets |
| $ | 576,732 |
| $ | 390,202 |
|
Liabilities and stockholders’ equity |
|
|
|
|
|
|
|
Current liabilities |
|
|
|
|
|
|
|
Accounts payable |
| $ | 3,797 |
| $ | 6,869 |
|
Accrued expenses |
|
| 9,662 |
|
| 5,480 |
|
Current portion of deferred rent |
|
| 315 |
|
| 26 |
|
Current portion of deferred revenue |
|
| 40,079 |
|
| 60,118 |
|
Income tax payable |
|
| — |
|
| 157 |
|
Total current liabilities |
|
| 53,853 |
|
| 72,650 |
|
Deferred rent, less current portion |
|
| 1,198 |
|
| 1,088 |
|
Total liabilities |
|
| 55,051 |
|
| 73,738 |
|
Commitments and contingencies (see note 8) |
|
|
|
|
|
|
|
Stockholders’ equity |
|
|
|
|
|
|
|
Preferred stock, $0.01 par value: 10,000,000 authorized shares; -0- issued and outstanding shares at December 31, 2018 and 2017 |
|
| — |
|
| — |
|
Common stock, $0.01 par value: 200,000,000 authorized shares; 56,279,542 issued and outstanding shares at December 31, 2018 and 47,002,488 issued and outstanding at December 31, 2017 |
|
| 563 |
|
| 470 |
|
Additional paid-in capital |
|
| 845,366 |
|
| 570,670 |
|
Accumulated other comprehensive loss |
|
| (971) |
|
| (1,808) |
|
Accumulated deficit |
|
| (323,277) |
|
| (252,868) |
|
Total stockholders’ equity |
|
| 521,681 |
|
| 316,464 |
|
Total liabilities and stockholders’ equity |
| $ | 576,732 |
| $ | 390,202 |
|
79
Xencor, Inc.
Statements of Comprehensive Income (Loss)
(in thousands, except share and per share data)
| | | | | | | | | | |
| | Year ended December 31, |
| |||||||
| | 2020 | | 2019 | | 2018 |
| |||
Revenue |
| |
|
| |
|
| |
| |
Collaborations, licenses, milestones and royalties | | $ | 122,694 | | $ | 156,700 | | $ | 40,603 | |
Operating expenses | | | | | | | | | | |
Research and development | | | 169,802 | |
| 118,590 | |
| 97,501 | |
General and administrative | | | 29,689 | |
| 24,286 | |
| 22,472 | |
Total operating expenses | | | 199,491 | |
| 142,876 | |
| 119,973 | |
Income (loss) from operations | |
| (76,797) | |
| 13,824 | |
| (79,370) | |
Other income (expense) | | | | | | | | | | |
Interest income, net | | | 7,264 | |
| 13,619 | |
| 9,086 | |
Other income (expense) | | | 200 | |
| (256) | |
| (125) | |
Total other income, net | | | 7,464 | |
| 13,363 | |
| 8,961 | |
| | | | | | | | | | |
Income (loss) before income tax | | | (69,333) | |
| 27,187 | |
| (70,409) | |
Income tax expense | | | — | | | 312 | | | — | |
Net income (loss) | | | (69,333) | | | 26,875 | | | (70,409) | |
Other comprehensive income (loss) | | | | | | | | | | |
Net unrealized gain (loss) on marketable securities available-for-sale | | | (1,087) | | | 2,132 | | | 837 | |
Comprehensive income (loss) | | $ | (70,420) | | $ | 29,007 | | $ | (69,572) | |
| | | | | | | | | | |
Net income (loss) per share attributable to common stockholders: | | | | | | | | | | |
Basic | | $ | (1.21) | | $ | 0.48 | | $ | (1.31) | |
Diluted | | $ | (1.21) | | $ | 0.46 | | $ | (1.31) | |
Weighted average shares used to compute net income (loss) per share attributable to common stockholders: | | | | | | | | | | |
Basic | | | 57,212,737 | |
| 56,531,439 | |
| 53,942,116 | |
Diluted | | | 57,212,737 | |
| 58,467,880 | |
| 53,942,116 | |
See accompanying notes to the financial statements.
80
Xencor, Inc.
Statements of Stockholders’ Equity
(in thousands, except share data)
| | | | | | | | | | | | | | | | | |
| | | | | | | | | | Accumulated | | | | | | | |
| | | | | | | Additional | | Other | | | | | Total | |||
| ��� | Common Stock | | Paid | | Comprehensive | | Accumulated | | Stockholders’ | |||||||
Stockholders’ Equity | | Shares | | Amount | | in-Capital | | | Income | | Deficit | | Equity | ||||
Balance, December 31, 2017 |
| 47,002,488 | | | 470 | | | 570,670 | | | (1,808) | | | (252,868) | | | 316,464 |
Sale of common stock, net of issuance cost | | 8,395,000 | | | 84 | | | 245,420 | | | — | | | — | | | 245,504 |
Issuance of common stock upon exercise of stock awards |
| 824,731 | | | 8 | | | 7,609 | | | — | | | — | | | 7,617 |
Issuance of common stock under the Employee Stock Purchase Plan | | 57,323 | | | 1 | | | 1,119 | | | — | | | — | | | 1,120 |
Comprehensive loss | | — | | | — | | | — | | | 837 | | | (70,409) | | | (69,572) |
Stock-based compensation | | — | | | — | | | 20,548 | | | — | | | — | | | 20,548 |
Balance, December 31, 2018 |
| 56,279,542 | | | 563 | | | 845,366 | | | (971) | | | (323,277) | | | 521,681 |
Issuance of common stock upon exercise of stock awards | | 543,887 | | | 5 | | | 9,264 | | | — | | | — | | | 9,269 |
Issuance of common stock under the Employee Stock Purchase Plan | | 67,561 | | | 1 | | | 1,392 | | | — | | | — | | | 1,393 |
Issuance of restricted stock units | | 11,311 | | | — | | | — | | | | | | | | | — |
Comprehensive income | | — | | | — | | | — | | | 2,132 | | | 26,875 | | | 29,007 |
Stock-based compensation | | — | | | — | | | 31,851 | | | — | | | — | | | 31,851 |
Balance, December 31, 2019 | | 56,902,301 | | | 569 | | | 887,873 | | | 1,161 | | | (296,402) | | | 593,201 |
Issuance of common stock upon exercise of stock awards | | 858,470 | | | 9 | | | 16,608 | | | — | | | — | | | 16,617 |
Issuance of common stock under the Employee Stock Purchase Plan | | 50,318 | | | 1 | | | 1,426 | | | — | | | — | | | 1,427 |
Issuance of restricted stock units | | 62,355 | | | 1 | | | (1) | | | — | | | — | | | — |
Comprehensive loss | | — | | | — | | | — | | | (1,087) | | | (69,333) | | | (70,420) |
Stock-based compensation | | — | | | — | | | 31,619 | | | — | | | — | | | 31,619 |
Balance, December 31, 2020 | | 57,873,444 | | $ | 580 | | $ | 937,525 | | $ | 74 | | $ | (365,735) | | $ | 572,444 |
See accompanying notes to the financial statements.
8281
Xencor, Inc.
(in thousands, except share and per share data)thousands)
|
|
|
|
|
|
|
|
|
|
|
|
| Year Ended December 31, |
| |||||||
|
| 2018 |
| 2017 |
| 2016 |
| |||
|
|
|
|
| (As Revised) |
| (As Revised) |
| ||
Revenue |
|
|
|
|
|
|
|
|
|
|
Collaborations, licenses and milestones |
| $ | 40,603 |
| $ | 46,150 |
| $ | 109,020 |
|
Operating expenses |
|
|
|
|
|
|
|
|
|
|
Research and development |
|
| 97,501 |
|
| 71,772 |
|
| 51,872 |
|
General and administrative |
|
| 22,472 |
|
| 17,501 |
|
| 13,108 |
|
Total operating expenses |
|
| 119,973 |
|
| 89,273 |
|
| 64,980 |
|
Income (loss) from operations |
|
| (79,370) |
|
| (43,123) |
|
| 44,040 |
|
Other income (expense) |
|
|
|
|
|
|
|
|
|
|
Interest income |
|
| 9,102 |
|
| 4,194 |
|
| 2,091 |
|
Interest expense |
|
| (16) |
|
| (13) |
|
| (21) |
|
Other income (expense) |
|
| (125) |
|
| (7) |
|
| 6 |
|
Total other income, net |
|
| 8,961 |
|
| 4,174 |
|
| 2,076 |
|
|
|
|
|
|
|
|
|
|
|
|
Income (loss) before income tax |
|
| (70,409) |
|
| (38,949) |
|
| 46,116 |
|
Income tax expense (benefit) |
|
| — |
|
| (463) |
|
| 991 |
|
Net income (loss) |
|
| (70,409) |
|
| (38,486) |
|
| 45,125 |
|
Other comprehensive income (loss) |
|
|
|
|
|
|
|
|
|
|
Net unrealized gain (loss) on marketable securities available-for-sale |
|
| 837 |
|
| (367) |
|
| (925) |
|
Comprehensive income (loss) |
| $ | (69,572) |
| $ | (38,853) |
| $ | 44,200 |
|
|
|
|
|
|
|
|
|
|
|
|
Net income (loss) per share attributable to common stockholders: |
|
|
|
|
|
|
|
|
|
|
Basic |
| $ | (1.31) |
| $ | (0.82) |
| $ | 1.09 |
|
Diluted |
| $ | (1.31) |
| $ | (0.82) |
| $ | 1.07 |
|
Weighted average shares used to compute net income (loss) per share attributable to common stockholders: |
|
|
|
|
|
|
|
|
|
|
Basic |
|
| 53,942,116 |
|
| 46,817,756 |
|
| 41,267,329 |
|
Diluted |
|
| 53,942,116 |
|
| 46,817,756 |
|
| 42,388,867 |
|
See accompanying notes to the financial statements.
83
Xencor, Inc.
Statements of Stockholders’ Equity
| | | | | | | | | | |
| | Year ended December 31, | | |||||||
| | 2020 | | 2019 | | 2018 |
| |||
Cash flows from operating activities |
| |
|
| |
|
| |
| |
Net income (loss) | | $ | (69,333) | | $ | 26,875 | | $ | (70,409) | |
Adjustments to reconcile net income (loss) to net cash provided by (used in) operating activities: | | | | | | | | | | |
Depreciation and amortization | | | 5,794 | |
| 4,298 | |
| 3,251 | |
Amortization of premium on marketable securities | | | (272) | | | (4,321) | | | (394) | |
Stock-based compensation | | | 31,619 | |
| 31,851 | |
| 20,548 | |
Abandonment of capitalized intangible assets | | | 535 | |
| 221 | |
| 239 | |
Loss on disposal of assets | |
| 4 | |
| 8 | |
| 102 | |
Loss (gain) on sale of marketable securities available-for-sale | | | (153) | | | — | | | 74 | |
Equity received in connection with license agreement | | | (26,660) | | | — | | | — | |
Cash redemption of equity received in connection with license agreement | | | 5,390 | | | — | | | — | |
Change in fair value of equity security | | | (105) | | | — | | | — | |
| | | | | | | | | | |
Changes in operating assets and liabilities: | | | | | | | | | | |
Accounts receivable | | | 10,131 | |
| (11,321) | |
| (9,045) | |
Interest receivable | | | 1,190 | | | (387) | | | (535) | |
Prepaid expenses and other current assets | | | (4,170) | |
| 3,828 | |
| (4,769) | |
Income tax receivable | | | 895 | | | 704 | | | (84) | |
Contract asset and deposits | | | (12,401) | | | — | | | (46) | |
Accounts payable | | | (1,235) | |
| 6,392 | |
| (3,072) | |
Accrued expenses | | | 8,608 | |
| (667) | |
| 4,182 | |
Deferred rent | | | — | | | (1,513) | | | 398 | |
Income tax payable | | | — | | | — | | | (157) | |
Lease liabilities and ROU assets | | | (325) | | | 1,354 | | | — | |
Deferred revenue | | | 45,484 | |
| 7,052 | |
| (20,039) | |
Net cash provided by (used in) operating activities | |
| (5,004) | |
| 64,374 | |
| (79,756) | |
Cash flows from investing activities | | | | | | | | | | |
Proceeds from sale and maturities of marketable securities available-for-sale | |
| 757,617 | |
| 456,923 | |
| 222,125 | |
Proceeds from sale of property and equipment | | | 1 | |
| — | |
| 9 | |
Purchase of marketable securities | | | (643,658) | | | (496,855) | | | (377,840) | |
Purchase of intangible assets | |
| (3,229) | |
| (3,685) | |
| (1,935) | |
Purchase of property and equipment | | | (10,539) | | | (7,353) | | | (7,212) | |
Proceeds from repayment of loan receivable | | | — | | | — | | | 86 | |
Net cash provided by (used in) investing activities | |
| 100,192 | |
| (50,970) | |
| (164,767) | |
Cash flows from financing activities | | | | | | | | | | |
Proceeds from issuance of common stock upon exercise of stock awards | | | 16,617 | |
| 9,269 | |
| 7,617 | |
Proceeds from issuance of common stock from Employee Stock Purchase Plan | | | 1,427 | |
| 1,393 | |
| 1,120 | |
Proceeds from issuance of common stock | | | — | |
| — | |
| 260,245 | |
Common stock issuance costs | |
| — | |
| — | |
| (14,741) | |
Net cash provided by financing activities | | | 18,044 | |
| 10,662 | |
| 254,241 | |
Net increase in cash and cash equivalents | | | 113,232 | |
| 24,066 | |
| 9,718 | |
Cash and cash equivalents, beginning of year | | | 50,312 | |
| 26,246 | |
| 16,528 | |
Cash and cash equivalents, end of year | | $ | 163,544 | | $ | 50,312 | | $ | 26,246 | |
Supplemental disclosures of cash flow information | | | | | | | | | | |
Cash paid for: | | | | | | | | | | |
Interest | | $ | 15 | | $ | 11 | | $ | 16 | |
Taxes | | $ | — | | $ | 400 | | $ | 233 | |
Supplemental Schedule of Noncash Investing Activities | | | | | | | | | | |
Net unrealized gain (loss) on marketable securities available-for-sale | | $ | (1,087) | | $ | 2,132 | | $ | 837 | |
(in thousands, except share data)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Accumulated |
|
|
|
|
|
| |
|
|
|
|
|
|
| Additional |
| Other |
|
|
|
| Total | |||
|
| Common Stock |
| Paid |
| Comprehensive |
| Accumulated |
| Stockholders’ | |||||||
Stockholders’ Equity |
| Shares |
| Amount |
| in-Capital |
|
| Loss |
| Deficit |
| Equity | ||||
Balance, December 31, 2015 as originally reported |
| 40,551,039 |
| $ | 405 |
| $ | 424,128 |
| $ | (516) |
| $ | (261,585) |
| $ | 162,432 |
Adoption of ASC Topic 606 |
| — |
|
| — |
|
| — |
|
| — |
|
| 2,479 |
|
| 2,479 |
Balance, December 31, 2015 as revised |
| 40,551,039 |
|
| 405 |
|
| 424,128 |
|
| (516) |
|
| (259,106) |
|
| 164,911 |
Sale of common stock, net of issuance cost |
| 5,272,750 |
|
| 53 |
|
| 119,216 |
|
| — |
|
| — |
|
| 119,269 |
Issuance of common stock upon exercise and vesting of stock awards |
| 699,066 |
|
| 7 |
|
| 1,153 |
|
| — |
|
| — |
|
| 1,160 |
Issuance of common stock under the Employee Stock Purchase Plan |
| 45,123 |
|
| 1 |
|
| 544 |
|
| — |
|
| — |
|
| 545 |
Comprehensive income (loss) |
| — |
|
| — |
|
| — |
|
| (925) |
|
| 45,125 |
|
| 44,200 |
Stock-based compensation |
| — |
|
| — |
|
| 7,848 |
|
| — |
|
| — |
|
| 7,848 |
Balance, December 31, 2016 |
| 46,567,978 |
|
| 466 |
|
| 552,889 |
|
| (1,441) |
|
| (213,981) |
|
| 337,933 |
Adoption of ASU 2016-09 |
| — |
|
| — |
|
| 401 |
|
| — |
|
| (401) |
|
| — |
Balance, December 31, 2016 as revised |
| 46,567,978 |
|
| 466 |
|
| 553,290 |
|
| (1,441) |
|
| (214,382) |
|
| 337,933 |
Issuance of common stock upon exercise of stock awards |
| 363,603 |
|
| 4 |
|
| 2,793 |
|
| — |
|
| — |
|
| 2,797 |
Issuance of common stock under the Employee Stock Purchase Plan |
| 70,907 |
|
| — |
|
| 936 |
|
| — |
|
| — |
|
| 936 |
Comprehensive loss |
| — |
|
| — |
|
| — |
|
| (367) |
|
| (38,486) |
|
| (38,853) |
Stock-based compensation |
| — |
|
| — |
|
| 13,651 |
|
| — |
|
| — |
|
| 13,651 |
Balance, December 31, 2017 |
| 47,002,488 |
|
| 470 |
|
| 570,670 |
|
| (1,808) |
|
| (252,868) |
|
| 316,464 |
Sale of common stock, net of issuance cost |
| 8,395,000 |
|
| 84 |
|
| 245,420 |
|
| — |
|
| — |
|
| 245,504 |
Issuance of common stock upon exercise of stock awards |
| 824,731 |
|
| 8 |
|
| 7,609 |
|
| — |
|
| — |
|
| 7,617 |
Issuance of common stock under the Employee Stock Purchase Plan |
| 57,323 |
|
| 1 |
|
| 1,119 |
|
| — |
|
| — |
|
| 1,120 |
Comprehensive income (loss) |
| — |
|
| — |
|
| — |
|
| 837 |
|
| (70,409) |
|
| (69,572) |
Stock-based compensation |
| — |
|
| — |
|
| 20,548 |
|
| — |
|
| — |
|
| 20,548 |
Balance, December 31, 2018 |
| 56,279,542 |
| $ | 563 |
| $ | 845,366 |
| $ | (971) |
| $ | (323,277) |
| $ | 521,681 |
See accompanying notes to the financial statements.
8482
Xencor, Inc.
(in thousands)
|
|
|
|
|
|
|
|
|
|
|
|
| Year ended December 31, |
| |||||||
|
| 2018 |
| 2017 |
| 2016 |
| |||
|
|
|
|
| (As Revised) |
| (As Revised) |
| ||
Cash flows from operating activities |
|
|
|
|
|
|
|
|
|
|
Net income (loss) |
| $ | (70,409) |
| $ | (38,486) |
| $ | 45,125 |
|
Adjustments to reconcile net income (loss) to net cash provided by (used in) operating activities: |
|
|
|
|
|
|
|
|
|
|
Depreciation and amortization |
|
| 3,251 |
|
| 2,030 |
|
| 1,466 |
|
Amortization of premium on marketable securities |
|
| (394) |
|
| 2,845 |
|
| 2,037 |
|
Stock-based compensation |
|
| 20,548 |
|
| 13,651 |
|
| 7,848 |
|
Abandonment of capitalized intangible assets |
|
| 239 |
|
| 396 |
|
| 356 |
|
Loss on disposal of assets |
|
| 102 |
|
| 83 |
|
| — |
|
Loss (gain) on sale of marketable securities available-for-sale |
|
| 74 |
|
| — |
|
| (5) |
|
|
|
|
|
|
|
|
|
|
|
|
Changes in operating assets and liabilities: |
|
|
|
|
|
|
|
|
|
|
Accounts receivable |
|
| (9,045) |
|
| 7,474 |
|
| (8,572) |
|
Interest receivable |
|
| (535) |
|
| (307) |
|
| (609) |
|
Prepaid expenses and other current assets |
|
| (4,769) |
|
| (2,705) |
|
| (1,700) |
|
Income tax receivable |
|
| (84) |
|
| (1,524) |
|
| — |
|
Other assets |
|
| (46) |
|
| (161) |
|
| (40) |
|
Accounts payable |
|
| (3,072) |
|
| 2,989 |
|
| (2,520) |
|
Accrued expenses |
|
| 4,182 |
|
| (1,212) |
|
| 3,058 |
|
Deferred rent |
|
| 398 |
|
| 589 |
|
| (89) |
|
Income tax payable |
|
| (157) |
|
| 91 |
|
| 65 |
|
Deferred revenue |
|
| (20,039) |
|
| (19,350) |
|
| 48,818 |
|
Net cash provided by (used in) operating activities |
|
| (79,756) |
|
| (33,597) |
|
| 95,238 |
|
Cash flows from investing activities |
|
|
|
|
|
|
|
|
|
|
Proceeds from sale and maturities of marketable securities available-for-sale |
|
| 222,125 |
|
| 115,757 |
|
| 105,505 |
|
Proceeds from sale of property and equipment |
|
| 9 |
|
| — |
|
| — |
|
Purchase of marketable securities |
|
| (377,840) |
|
| (76,529) |
|
| (316,149) |
|
Purchase of intangible assets |
|
| (1,935) |
|
| (1,967) |
|
| (1,502) |
|
Purchase of property and equipment |
|
| (7,212) |
|
| (5,311) |
|
| (1,507) |
|
Proceeds from repayment of (investment in) loan receivable |
|
| 86 |
|
| (86) |
|
| (621) |
|
Net cash provided by (used in) investing activities |
|
| (164,767) |
|
| 31,864 |
|
| (214,274) |
|
Cash flows from financing activities |
|
|
|
|
|
|
|
|
|
|
Proceeds from issuance of common stock upon exercise of stock awards |
|
| 7,617 |
|
| 2,797 |
|
| 1,160 |
|
Proceeds from issuance of common stock from Employee Stock Purchase Plan |
|
| 1,120 |
|
| 936 |
|
| 545 |
|
Proceeds from issuance of common stock |
|
| 260,245 |
|
| — |
|
| 126,546 |
|
Common stock issuance costs |
|
| (14,741) |
|
| — |
|
| (7,277) |
|
Net cash provided by financing activities |
|
| 254,241 |
|
| 3,733 |
|
| 120,974 |
|
Net increase in cash and cash equivalents |
|
| 9,718 |
|
| 2,000 |
|
| 1,938 |
|
Cash and cash equivalents, beginning of year |
|
| 16,528 |
|
| 14,528 |
|
| 12,590 |
|
Cash and cash equivalents, end of year |
| $ | 26,246 |
| $ | 16,528 |
| $ | 14,528 |
|
Supplemental disclosures of cash flow information |
|
|
|
|
|
|
|
|
|
|
Cash paid for: |
|
|
|
|
|
|
|
|
|
|
Interest |
| $ | 16 |
| $ | 13 |
| $ | 21 |
|
Taxes |
| $ | 233 |
| $ | 969 |
| $ | 936 |
|
Supplemental Schedule of Noncash Investing Activities |
|
|
|
|
|
|
|
|
|
|
Net unrealized gain (loss) on marketable securities available-for-sale |
| $ | 837 |
| $ | (367) |
| $ | (925) |
|
See accompanying notes to the financial statements.
1. Summary of Significant Accounting Policies
Description of Business
Xencor, Inc. (we, us, our, or the Company) was incorporated in California in 1997 and reincorporated in Delaware in September 2004. We are a clinical‑stageclinical-stage biopharmaceutical company focused on discovering and developing engineered monoclonal antibody and proteinscytokine therapeutics to treat severepatients with cancer and life‑threateningautoimmune diseases withwho have unmet medical needs. We usecreate our product candidates using our proprietary XmAb technology platform to create next‑generation antibody product candidates designed to treat cancer, autoimmune and allergic diseases, and other conditions. Weplatforms, which focus on the portion of thean antibody that interacts with multiple segments of the immune system, referred to as the Fc domain, which is constant and interchangeable among antibodies. Our engineered Fc domains, the XmAb technology, are applied to our pipeline ofcan increase antibody and protein‑based drug candidates to increase immune inhibition, improve cytotoxicity, extend half‑lifehalf-life and most recently are used to create bispecific Fc domain antibodyantibodies and protein molecules.cytokines.
Our operations are based in Monrovia, California and San Diego, California.
Basis of Presentation
The Company’s financial statements as of December 31, 2018, 2017,2020, 2019, and 20162018 and for the years then ended have been prepared in accordance with accounting principles generally accepted in the United States (U.S.).
Use of Estimates
The preparation of financial statements in conformity with accounting principles generally accepted in the United States of America requires management to make estimates and assumptions that affect the amounts reported in the financial statements and accompanying notes. Significant estimates include useful lives of long-lived assets, the periods over which certain revenues and expenses will be recognized including collaboration revenue recognized from non-refundable upfront licensing payments, the amount of non-cash compensation costs related to share-based payments to employees and non-employees and the period over which these costs are expensed.
Recent Accounting Pronouncements
Pronouncements adopted in 20182020
Effective January 1, 2018, the Company adopted Accounting Standards Codification Topic 606 (ASC 606), Revenue from Contracts with Customers, using the full retrospective transition method. Under this method, the Company is presenting its financial statements for the years ended December 31, 2017 and 2016 as if ASC 606 had been effective for those periods.
Under ASC 606 an entity recognizes revenue when its customer obtains control of promised goods or services in an amount that reflects the consideration which the entity expects to receive in exchange for those goods or services. A five-step model is used to achieve the core principle: (1) identify the customer contract, (2) identify the contract’s performance obligations, (3) determine the transaction price, (4) allocate the transaction price to the performance obligations and (5) recognize revenue when or as a performance obligation is satisfied. The Company applies the five-step model to contracts when it is probable that the entity will collect the consideration it is entitled to in exchange for the goods or services it transfers to the customer. The new guidance provides that revenue recognition for performance obligations related to delivery of certain goods or services occurs when control over the good or service is transferred to the customer. In addition, the timing of revenue recognition from licensing of our intellectual property that are functional and are distinct performance obligations changed from being recognized over the term of access to our license or technology to being recognized at a point in time. See Note 12 “Prior Period Financial Statements” for a complete discussion of the impact of adopting the new standard.
86
Effective January 1, 2018, the Company adopted ASU 2016-01, Financial Instruments – Overall: Recognition and Measurement of Financial Assets and Liabilities, which eliminates the available-for-sale classification for equity securities and requires equity securities to be measured at fair value with changes in the fair value recognized through net income. This ASU eliminates the available-for-sale classification for equity investments that recognized changes in the fair value as a component of other comprehensive income. The adoption had no effect on the Company’s financial statements.
Effective January 1 2018,2020, the Company adopted ASU No. 2016-15, Statement of Cash Flows (Topic 230): Classification of Certain Cash Receipts and Cash Payments, which addresses eight specific cash flow issues with the objective of reducing the existing diversity in practice. The standard clarifies when cash receipts and cash payments have aspects of more than one class of cash flows and cannot be separated. Classification will depend on the predominant source or use. The adoption did not have an effect on the Company’s statements of cash flow.
Effective January 1, 2018, the Company adopted ASU No. 2017-09, Compensation – Stock Compensation (Topic 718). The standard applies when a company changes the terms of a stock compensation award previously granted to an employee where modification accounting applies. According to the standard, modification accounting is not required if (1) the fair value of the modified award (or the award’s calculated value or intrinsic value as appropriate) is the same as the value immediately prior to its modification, (2) the vesting conditions of the modified award are the same as the vesting conditions of the award immediately prior to its modification; and (3) the award’s classification as an equity or liability is the same after the modification as it was immediately prior to its modification. The Company did not have any modifications upon adopting the new standard; therefore, adoption had no effect on the Company’s financial statements.
Pronouncements not yet effective
In February 2016, the FASB issued ASU No. 2016-02 Leases (Topic 842). The new guidance requires lessees to recognize in the statement of financial position a liability to make lease payments (the lease liability) and a right-of-use asset representing its right to use the underlying asset for the lease term for all leases not considered short term. The new standard will be effective for reporting periods beginning after December 15, 2018. In July 2018, the FASB issued ASU No. 2018-10 Codification Improvements to Topic 842, Leases and ASU No. 2018-11, Lease (Topic 842): Targeted Improvements, which provides narrow aspects of the guidance issued in ASU No. 2016-02 as well as an alternative transition method of adoption, permitting the recognition of cumulative-effect adjustment to retained earnings on the date of adoption. The new standard also provides a number of optional practical expedients in transition, including the “package of practical expedients,” which permits us not to reassess under the new standard our prior conclusions about lease identification, lease classification and initial direct cost.
We will adopt the new standard on January 1, 2019 using the cumulative effect adjustment method, with the election of the package of practical expedients and hindsight practical expedient. We have completed a preliminary assessment of the new standard’s impact, which includes a total of five operating leases for facilities in Monrovia and San Diego. Under Topic 842, deferred rent liability under operating lease is no longer tracked separately; instead, it will integrate as part of the right-of-use (ROU) asset. As a result, we expect to adjust the cumulative effect to the beginning balance for deferred rent liability, and adopt the use of right-of-use asset and lease liability. We do not expect that this standard will have a material impact on our financial statements. Upon adoption, we estimate that we will have additional liabilities ranging from $10 million to $12 million with a corresponding ROU assets of a similar amount for lease agreements in effect as of December 31, 2018. This will result in an estimated increase to the beginning balance on both assets and liabilities after the adjustment of between $10 million and $12 million, with no impact on our retained earnings.
87
In June 2016, the FASB issued ASU No. 2016-13, Financial Instruments – Credit Losses (Topic 326): Measurement of Credit Losses on Financial Instruments,, which as well as ASU No, 2018-19, Codification Improvements to Topic 326, Financial Instruments – Credit Losses. The standard amends the guidance on reporting credit losses for assets held at amortized cost basis and also provides an available-for-sale (AFS) debt securities. Credit losses relating to available-for-salesecurity impairment model that is a modified version of the other-than-temporary-impairment (OTTI) model. The AFS debt securities will be recorded through an allowance for credit losses rathersecurity impairment model no longer allows consideration of the length of time during which the fair value has been less than as a direct write-down to the security. Credit losses on available-for-sale securities will be required when theits amortized cost is below the fair market value.when determining whether a credit loss exists. The amendment is effective for fiscal years beginning after December 15, 2019 including interim periods within those fiscal years. In November 2018, the FASB issued ASU No. 2018-19, Codification Improvements to Topic 326, Financial Instruments – Credit Losses, which clarifies that receivables arising from operating leases areadoption of this standard did not within the scope of Topic 326. We will apply the standard’s provision as a cumulative effect adjustment to retained earnings as of the beginning of the first effective reporting period. We do not expect the adoption to have a materialany impact on our results of operations orthe Company’s financial position.statements.
In March 2017,Effective January 1, 2020, the FASB issued ASU No. 2017-08, Receivables – Nonrefundable Fees and Other Costs (Subtopic 310-20): Premium Amortization on Purchased Callable Debt Securities, which amends the guidance on the amortization period of premiums on certain purchased callable debt securities by shortening the amortization period of premiums to the earliest call date. The amendment affects all entities that hold investments in callable debt securities that have an amortized cost basis in excess of the amount that is repayable by the issuer at the earliest call date. The amendment is effective for fiscal years after December 31, 2018 with early adoption permitted. The Company will review the requirements of the standard but does not anticipate it will have a significant impact on our financial statements.
In February 2018, the FASB issued ASU No. 2018-02. Income Statement – Reporting Comprehensive Income (Topic 220): Reclassification of Certain Tax Effects from Accumulated Other Comprehensive Income, an amendment which permits companies to reclassify the income tax effects of the 2017 Tax Cuts and Jobs Act (TCJA) on items within accumulated other comprehensive income to retained earnings. The standard also requires new disclosures about these stranded tax effects and is effective for fiscal years beginning after December 15, 2018 and interim periods within those fiscal years. Early adoption is permitted and can be applied either in the period of adoption or retrospectively to each period (or periods) in which the effect of the change in the U.S. federal corporate income tax rate in the TCJA is recognized. The Company is currently evaluating the impact the guidance will have on its financial statements.
In June 2018, the FASB issued ASU No. 2018-07, Compensation – Stock Compensation (Topic 718): Improvements to Nonemployee Share-Based Payment Accounting, which expands the scope of Topic 718 to include share-based payments issued to nonemployees for goods and services. The standard is effective for fiscal years beginning after December 15, 2018 and interim periods within such fiscal year. The Company does not anticipate that the standard will have a significant impact on its financial statements.
In August 2018, the FASB issuedadopted ASU No. 2018-13, Fair Value Measurement (Topic 820): Disclosure Framework – Changes to the Disclosure Requirements for Fair Value Measurement,, which modifies the disclosures for transfers between Level 1 and Level 2 of the fair value hierarchy, modifies the levelLevel 3 disclosure requirements for non-public entities and requires additional disclosure for Level 3 fair value hierarchy. The amendment is effective for fiscal years beginning after December 15, 2019. The Company doesadoption of this standard did not anticipate that the standard will have a significantany impact on its financial statements.
In August 2018, the FASB issued ASU No. 2018-15, Intangibles – Goodwill and Other – Internal Use Software (Subtopic 350-40): Customer’s Accounting for Implementation Costs Incurred in a Cloud Computing Arrangement that is a Service Contract, which aligns the requirements for capitalizing implementation costs incurred in a hosting arrangement that is a service contract with the requirements for capitalizing implementation costs incurred to develop or obtain internal-use software (and hosting arrangements that include an internal-use software license). The accounting for the service element of a hosting arrangement that is a service contract is not affected by the amendment. The amendment is effective for annual periods, including interim periods within those annual periods, beginning after December 15, 2019. The Company does not anticipate that the standard will have a significant impact on its financial statements.
88
In October 2018, the FASB issued ASU No. 2018-17, Consolidation (Topic 810): Targeted Improvements to Related Party Guidance for Variable Interest Entities, which amends the guidance for determining whether a decision-making fee is a variable interest. The amendments require organizations to consider indirect interests held through related parties under common control on a proportional basis rather than as the equivalent of a direct interest in its entirety (as currently required). The Company does not anticipate that the standard will have a significant impact on tisCompany’s financial statements.
In November 2018,Effective January 1, 2020, the FASB issuedCompany adopted ASU No. 2018-18, Collaborative Arrangements (Topic 808): Clarifying the Interaction Between Topic 808 and Topic 606, which provides guidance on how to assess whether certain transactions between collaborative arrangement participants should be accounted for within the revenue recognition standard. The adoption of this standard did not have any impact on the Company’s financial statements.
83
Pronouncements not yet effective
In December 2019, the FASB issued ASU No. 2019-12, Income Taxes (Topic 740): Simplifying the Accounting for Income Taxes, which is effective for fiscal years beginning after December 15, 20192020, and interim periodperiods within those fiscal years. The standard removes specific exceptions to the general principles in Topic 740 and simplifies the accounting for income taxes. The Company does not anticipate that the standard will have a significant impact on its financial statements.
In January 2020, the FASB issued ASU No. 2020-01, which clarifies that a company should consider observable transactions that require a company to either apply or discontinue the equity method of accounting under Topic 323, Investment – Equity Method and Joint Ventures, for the purposes of applying the measurement alternative in accordance with Topic 321, Investments – Equity Securities immediately before applying or upon discontinuing the equity method. The amendment is effective for fiscal years beginning after December 15, 2020. The Company does not anticipate that the standard will have a significant impact on its financial statements.
In October 2020, the FASB issued ASU No. 2020-10, Codification Improvements, which amends a variety of topics in the Accounting Standards Codification to improve consistency and clarify guidance. The amendment is effective for fiscal years beginning after December 15, 2020. The Company is currently evaluating the amendment and does not anticipate that it will have an impact on its financial statements.
Revenue Recognition
We have, to date, earned revenue from research and development collaborations, which may include research and development services, licenses of our internally-developedinternally developed technologies, licenses of our internally-developedinternally developed drug candidates, or combinations of these.
The terms of our license, and research and development and collaboration agreements generally include non-refundable upfront payments, research funding, co-development payments and reimbursements, license fees, and milestone and other contingent payments to us for the achievement of defined collaboration objectives and certain clinical, regulatory and sales‑basedsales-based events, as well as royalties on sales of any commercialized products.
The terms of our licensing agreements include non‑refundablenon-refundable upfront fees, annual licensing fees, and contractual payment obligations for the achievement of pre‑definedpre-defined preclinical, clinical, regulatory and sales‑basedsales-based events by our partners. The licensing agreements also include royalties on sales of any commercialized products by our partners.
We recognize revenue through the five-step process in accordance with ASC 606 Revenue Recognition when control of the promised goods or services is transferred to our customers in an amount that reflects the consideration we expect to be entitled to in exchange for those goods or services.
Deferred Revenue
Deferred revenue arises from payments received in advance of the culmination of the earnings process. We have classified deferred revenue for which we stand ready to perform within the next 12 months as a current liability. We recognize deferred revenue as revenue in future periods when the applicable revenue recognition criteria have been met. The total amounts reported as deferred revenue were $40.1$92.6 million and $60.1$47.1 million at December 31, 20182020 and 2017,2019, respectively.
Research and Development Expenses
Research and development expenses include costs we incur for our own and for our collaborators’ research and development activities. Research and development costs are expensed as incurred. These costs consist primarily of salaries and benefits, including associated stock‑basedstock-based compensation, laboratory supplies, facility costs, and applicable overhead expenses of personnel directly involved in the research and development of new technology and products, as
84
well as fees paid to other entities that conduct certain research development activities on our behalf. We estimate preclinical study and clinical trial expenses based on the services performed pursuant to the contracts with research institutions and clinical research organizations that conduct and manage preclinical studies and clinical trials on our behalf based on the actual time and expenses incurred by them. Further, we accrue expenses related to clinical trials based on the level of patient enrollment and activity according to the related agreement. We monitor patient enrollment levels and related activity to the extent reasonably possible and adjust estimates accordingly.
89
We capitalize acquired research and development technology licenses and third‑partythird-party contract rights where such assets have an alternative use and amortize the costs over the shorter of the license term or the expected useful life. We review the license arrangements and the amortization period on a regular basis and adjust the carrying value or the amortization period of the licensed rights if there is evidence of a change in the carrying value or useful life of the asset.
Cash and Cash Equivalents
We consider cash equivalents to be only those investments which are highly liquid, readily convertible to cash and which mature within three months from the date of purchase.
Marketable and Equity Securities
The Company has an investment policy that includes guidelines on acceptable investment securities, minimum credit quality, maturity parameters and concentration and diversification. The Company invests its excess cash primarily in marketable debt securities issued by investment grade institutions.
The Company considers its marketable debt securities to be “available-for-sale”, as defined by authoritative guidance issued byavailable-for-sale and does not intend to sell these securities, and it is not more likely than not the FASB.Company will be required to sell the securities before recovery of the amortized cost basis. These assets are carried at fair value and any impairment losses and recoveries related to the unrealized gainsunderlying issuer’s credit standing are recognized within other income (expense), while non-credit related impairment losses and lossesrecoveries are included inrecognized within accumulated other comprehensive income (loss). There were 0 impairment losses or recoveries recorded for the years ended in December 31, 2020 and 2019, respectively. Accrued interest on marketable debt securities is included in marketable securities.securities’ carrying value. Accrued interest was $2.3$1.4 million and $1.7$2.7 million at December 31, 20182020 and 2017,2019, respectively. If a decline inEach reporting period, the value of a marketable security in the Company’s investment portfolio is deemed to be other-than-temporary, the Company writes down the security to its current fair value and recognizes a loss as a charge against income. The Company reviews its portfolio of marketable debt securities, using both quantitative and qualitative factors, to determine if declineseach security’s fair value has declined below its amortized cost basis.
The Company receives equity securities in connection with certain licensing transactions with its partners. These investments in an equity security are carried at fair value with changes in fair value belowrecognized each period and reported within other income (expense). For equity securities with a readily determinable fair value, the Company remeasures these equity investments at each reporting period until such time that the investment is sold or disposed. If the Company sells an investment, any realized gains or losses on the sale of the securities will be recognized within other income (expense) in the Statement of Comprehensive Income (Loss) in the period of sale.
The Company also has an investment in an equity security without a readily determinable fair value, where the Company elects the measurement alternative to record at its initial cost are other-than-temporary.minus impairment, plus or minus changes resulting from observable price changes in orderly transactions for the identical or a similar investment of the same issuer.
Concentrations of Risk
Cash, cash equivalents and marketable debt securities are financial instruments that potentially subject the Company to concentrations of risk. We invest our cash in corporate debt securities and U.S. sponsored agencies with strong credit ratings. We have established guidelines relative to diversification and maturities that are designed to help ensure safety and liquidity. These guidelines are periodically reviewed to take advantage of trends in yields and interest rates.
85
Cash and cash equivalents are maintained at financial institutions, and at times, balances may exceed federally insured limits. We have never experienced any losses related to these balances. Amounts on deposit in excess of federally insured limits at December 31, 20182020 and 20172019 approximated $26.0$163.3 million and $16.3$50.0 million, respectively.
We have payables with four1 service providersprovider that represent 49% of our total payables and twowith 2 service providers that represented 40%48% of our total payables at December 31, 20182020 and 2017,2019, respectively. We rely on three3 critical suppliers for the manufacture of our drug product for use in our clinical trials. While we believe that there are alternative vendors available, a change in manufacturing vendors could cause a delay in the availability of drug product and result in a delay of conducting and completing our clinical trials. No other vendor accounted for more than 10% of total payables at December 31, 20182020 or 2017.2019.
Fair Value of Financial Instruments
Our financial instruments primarily consist of cash and cash equivalents, marketable debt securities, accounts receivable, accounts payable and accrued expenses. Marketable debt securities and cash equivalents are carried at fair value. The fair value of the other financial instruments closely approximate their fair value due to their short maturities.
90
The Company accounts for recurring and non-recurring fair value measurements in accordance with FASB Accounting Standards Codification (ASC) 820, Fair Value Measurements and Disclosures (ASC 820). ASC 820 defines fair value, establishes a fair value hierarchy for assets and liabilities measured at fair value, and requires expanded disclosure about fair value measurements. The ASC 820 hierarchy ranks the quality of reliable inputs, or assumptions, used in the determination of fair value and requires assets and liabilities carried at fair value to be classified and disclosed in one of the following three categories:
Level 1—Fair Valuevalue is determined by using unadjusted quoted prices that are available in active markets for identical assets or liabilities.
Level 2—Fair Valuevalue is determined by using inputs other than Level 1 quoted prices that are directly or indirectly observable. Inputs can include quoted prices for similar assets or liabilities in active markets or quoted prices for identical assets or liabilities in markets that are not active. Related inputs can also include those used in valuation or other pricing models, such as interest rates and yield curves that can be corroborated by observable market data.
Level 3—Fair value is determined by inputs that are unobservable and not corroborated by market data. Use of these inputs involves significant and subjective judgments to be made by the reporting entity –e.g. determining an appropriate discount factor for illiquidity associated with a given security.
86
The Company measures the fair value of financial assets using the highest level of inputs that are reasonably available as of the measurement date. The assets recorded at fair value are classified within the hierarchy as follows for the periods reported (in thousands):
|
|
|
|
|
|
|
|
|
| ||||||||||||
|
| December 31, 2018 | |||||||||||||||||||
|
| Total |
|
|
|
|
|
| |||||||||||||
|
| Fair Value |
| Level 1 |
| Level 2 | |||||||||||||||
|
|
|
|
|
|
|
|
|
| ||||||||||||
| | | | | | | | | | | | | |||||||||
| | December 31, 2020 | |||||||||||||||||||
|
| Total |
|
| | | | | | | | ||||||||||
| | Fair Value | | Level 1 | | Level 2 | | Level 3 | |||||||||||||
| | | | | | | | | | | | | |||||||||
Money Market Funds in Cash and Cash Equivalents |
| $ | 18,270 |
| $ | 18,270 |
| $ | — | | $ | 158,937 | | $ | 158,937 | | $ | — | | $ | — |
Corporate Securities |
|
| 104,967 |
|
| — |
|
| 104,967 | | | 119,833 | | | — | | | 119,833 | | | — |
Government Securities |
|
| 399,256 |
|
| — |
|
| 399,256 | | | 315,353 | | | — | | | 315,353 | | | — |
|
| $ | 522,493 |
| $ | 18,270 |
| $ | 504,223 | ||||||||||||
|
|
|
|
|
|
|
|
|
| ||||||||||||
|
| December 31, 2017 | |||||||||||||||||||
|
| Total |
|
|
|
|
|
| |||||||||||||
|
| Fair Value |
| Level 1 |
| Level 2 | |||||||||||||||
|
|
|
|
|
|
|
|
|
| ||||||||||||
Equity Securities with Readily Determinable Fair Value | | | 5,303 | | | 5,303 | | | — | | | — | |||||||||
Equity Securities without Readily Determinable Fair Value | | | 16,071 | | | — | | | — | | | 16,071 | |||||||||
| | $ | 615,497 | | $ | 164,240 | | $ | 435,186 | | $ | 16,071 | |||||||||
| | | | | | | | | | | | | |||||||||
| | December 31, 2019 | |||||||||||||||||||
|
| Total |
|
| | | | | | | | ||||||||||
| | Fair Value | | Level 1 | | Level 2 | | Level 3 | |||||||||||||
| | | | | | | | | | | | | |||||||||
Money Market Funds in Cash and Cash Equivalents |
| $ | 5,175 |
| $ | 5,175 |
| $ | — | | $ | 32,009 | | $ | 32,009 | | $ | — | | $ | — |
Corporate Securities |
|
| 123,270 |
|
| — |
|
| 123,270 | | | 281,751 | | | — | | | 281,751 | | | — |
Government Securities |
|
| 223,530 |
|
| — |
|
| 223,530 | | | 269,245 | | | — | | | 269,245 | | | — |
|
| $ | 351,975 |
| $ | 5,175 |
| $ | 346,800 | ||||||||||||
| | $ | 583,005 | | $ | 32,009 | | $ | 550,996 | | $ | — | |||||||||
The Company holds equity securities without readily determinable fair value as of December 31, 2020. The Company elects the measurement alternative to record at its initial cost minus impairment, plus or minus changes resulting from observable price changes in orderly transactions for the identical or a similar investment of the same issuer.
Property and Equipment
Property and equipment are recorded at cost and depreciated using the straight‑linestraight-line method over the estimated useful lives of the assets. Expenditures for repairs and maintenance are charged to expense as incurred, while renewals and improvements are capitalized. Useful lives by asset category are as follows:
| | | |
|
|
| |
| |||
Computers, software and equipment |
| 3 - 5 years | |
Furniture and fixtures |
| 5 - 7 years | |
Leasehold improvements |
| 5 - 7 years or remaining | |
| | lease term, whichever is less | |
9187
Patents, Licenses, and Other Intangible Assets
The cost of acquiring licenses is capitalized and amortized on the straight‑linestraight-line basis over the shorter of the term of the license or its estimated economic life, ranging from five5 to 25 years. Third‑partyThird-party costs incurred for acquiring patents are capitalized. Capitalized costs are accumulated until the earlier of the period that a patent is issued, or we abandon the patent claims. Cumulative capitalized patent costs are amortized on a straight‑linestraight-line basis from the date of issuance over the shorter of the patent term or the estimated useful economic life of the patent, ranging from 13 to 20 years. Our senior management, with advice from outside patent counsel, assesses three3 primary criteria to determine if a patent will be capitalized initially: i) technical feasibility, ii) magnitude and scope of new technical function covered by the patent compared to the company’s existing technology and patent portfolio, particularly assessing the value added to our product candidates or licensing business, and iii) legal issues, primarily assessment of patentability and prosecution cost. We review our intellectual property on a regular basis to determine if there are changes in the estimated useful life of issued patents and if any capitalized costs for unissued patents should be abandoned. Capitalized patent costs related to abandoned patent filings are charged off in the period of the decision to abandon. During 2018, 20172020, 2019 and 2016,2018, we abandoned previously capitalized patent and licensing related charges of $0.5 million, $0.2 million $0.4 million and $0.4$0.2 million, respectively.
The carrying amount and accumulated amortization of patents, licenses, and other intangibles is as follows (in thousands):
|
|
|
|
|
|
|
|
|
| December 31, |
| ||||
|
| 2018 |
| 2017 |
| ||
Patents, definite life |
| $ | 9,320 |
| $ | 8,915 |
|
Patents, pending issuance |
|
| 5,644 |
|
| 4,360 |
|
Licenses and other amortizable intangible assets |
|
| 2,011 |
|
| 2,011 |
|
Nonamortizable intangible assets (trademarks) |
|
| 399 |
|
| 399 |
|
Total gross carrying amount |
|
| 17,374 |
|
| 15,685 |
|
Accumulated amortization—patents |
|
| (4,142) |
|
| (3,413) |
|
Accumulated amortization—licenses and other |
|
| (1,263) |
|
| (1,124) |
|
Total intangible assets, net |
| $ | 11,969 |
| $ | 11,148 |
|
| | | | | | | |
| | December 31, |
| ||||
| | 2020 | | 2019 |
| ||
Patents, definite life |
| $ | 12,038 |
| $ | 10,597 | |
Patents, pending issuance | | | 8,432 | |
| 7,266 | |
Licenses and other amortizable intangible assets | | | 2,560 | |
| 2,510 | |
Nonamortizable intangible assets (trademarks) | | | 399 | |
| 399 | |
Total gross carrying amount | | | 23,429 | |
| 20,772 | |
Accumulated amortization—patents | | | (5,791) | |
| (4,912) | |
Accumulated amortization—licenses and other | | | (1,661) | |
| (1,439) | |
Total intangible assets, net | | $ | 15,977 | | $ | 14,421 | |
Amortization expense for patents, licenses, and other intangible assets was $1.1 million, $0.9 million $0.8 million, and $0.8$0.9 million for the years ended December 31, 2018, 20172020, 2019 and 2016,2018, respectively.
Future amortization expense for patent, licenses, and other intangible assets recorded as of December 31, 2018,2020, and for which amortization has commenced, is as follows:
|
|
|
|
|
|
| Year ended |
| |
|
| December 31, |
| |
|
| (in thousands) |
| |
2019 |
| $ | 862 |
|
2020 |
|
| 860 |
|
2021 |
|
| 757 |
|
2022 |
|
| 730 |
|
2023 |
|
| 659 |
|
Thereafter |
|
| 1,923 |
|
Total |
| $ | 5,791 |
|
| | | | |
|
| Year ended |
| |
| | December 31, |
| |
| | (in thousands) |
| |
2021 | | $ | 947 | |
2022 | | | 906 | |
2023 | | | 829 | |
2024 | | | 667 | |
2025 | | | 589 | |
Thereafter | | | 3,208 | |
Total | | $ | 7,146 | |
The above amortization expense forecast is an estimate. Actual amounts of amortization expense may differ from estimated amounts due to additional intangible asset acquisitions, impairment of intangible assets, accelerated amortization of intangible assets, and other events. As of December 31, 2018,2020, the Company has $5.6$8.4 million of intangible assets which are in‑processin-process and have not been placed in service, and accordingly amortization on these assets has not commenced.
9288
Long‑LivedLong-Lived Assets
Management reviews long‑livedlong-lived assets which include fixed assets and amortizable intangibles for impairment whenever events or changes in circumstances indicate that the carrying amount of an asset (or asset group) 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 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 as the amount by which the carrying amount of the assets exceeds the fair value of the assets.
We did not recognize a loss from impairment for the years ended December 31, 2018, 20172020, 2019 or 2016.2018.
Income Taxes
We account for income taxes in accordance with accounting guidance which requires an asset and liability approach to financial accounting and reporting for income taxes. Deferred income tax assets and liabilities are computed annually for differences between the financial statement and tax bases of assets and liabilities that will result in taxable or deductible amounts in the future based on enacted tax laws and rates applicable to the periods in which the differences are expected to affect taxable income. Valuation allowances are established when necessary to reduce deferred tax assets to the amount expected to be realized. Income tax expense is the tax payable or refundable for the period plus or minus the change during the period in deferred tax assets and liabilities.
We assess our income tax positions and record tax benefits for all years subject to examination based upon our evaluation of the facts, circumstances and information available at the reporting date. For those tax positions where there is greater than 50% likelihood that a tax benefit will be sustained, we have recorded the largest amount of tax benefit that may potentially be realized upon ultimate settlement with a taxing authority that has full knowledge of all relevant information. For those income tax positions where there is a 50% or less likelihood that a tax benefit will be sustained, no tax benefit has been recognized in the financial statements. We did not have any material uncertain tax positions at December 31, 20182020 or 2017.2019.
Our policy is to recognize interest and penalties on taxes, if any, as a component of income tax expense.
The Tax Cuts and Jobs Act (tax reform) wasof 2017 (TCJA) enacted on December 22, 2017 and hasincluded several key provisions impacting the accounting for and reporting of income taxes. The most significant provisions reduced the U.S. corporate statutory tax rate from 35% to 21%, eliminated the corporate Alternative Minimum Tax (AMT) system, and made changes to the utilization and carryforward of net operating losses beginning on January 1, 2018. The tax reform provided for a refund of unused AMT carryforwards for years beginning after December 31, 2017. We recordedreceived an income tax receivable as ofrefund during the years ended December 31, 20182020 and 2019 of $1.6$0.8 million each year related to our federal AMT carryforwards.
Stock‑BasedStock-Based Compensation
We recognize compensation expense using a fair‑value‑basedfair-value-based method for costs related to all share‑basedshare-based payments, including stock options, restricted stock units (RSUs), and shares issued under our Employee Stock Purchase Plan (ESPP). Stock‑basedStock-based compensation cost related to employees and directors is measured at the grant date, based on the fair‑value-basedfair-value-based measurement of the award using the Black‑ScholesBlack-Scholes method, and is recognized as expense over the requisite service period on a straight‑linestraight-line basis. We account for forfeitures when they occur. We recorded stock‑basedstock-based compensation and expense for stock‑basedstock-based awards to employees, directors and consultants of approximately $20.5$31.6 million, $13.7$31.9 million and $7.8$20.5 million for the years ended December 31, 2018, 20172020, 2019 and 20162018 respectively. Included in the 2018, 2017,2020, 2019, and 20162018 balances for total compensation expense is $0.8 million, $0.7 million $0.5 million, and $0.4$0.7 million, respectively, relating to our ESPP.
Options granted to individual service providers that are not employees or directors are accounted for at estimated fair value using the Black‑Scholes option‑pricing method and are subject to periodic re‑measurement over the period during which the services are rendered.
93
Net Income (Loss) Per Share
Basic net income (loss) per common share is computed by dividing the net income or loss by the weighted‑averageweighted-average number of common shares outstanding during the period. Potentially dilutive securities consistingwere included
89
in the diluted net lossincome per common share calculation for 2019. We included 1,923,310 options to purchase shares of common stock and 13,131 shares of RSUs in the calculation of the weighted-average common shares outstanding used in computing diluted net income per common share. We excluded 1,022,623 shares of options and RSUs from the calculation for 2019 because the inclusion of such shares would have had an antidilutive effect as follows:effect.
|
|
|
|
|
|
|
|
|
| Year Ended |
| ||||
|
| December 31, |
| ||||
|
| 2018 |
| 2017 |
| 2016 |
|
|
| (in thousands) |
| ||||
Options to purchase common stock |
| 1,881 |
| 1,291 |
| — |
|
Employee stock purchase plan shares |
| 3 |
| — |
| — |
|
Total |
| 1,884 |
| 1,291 |
| — |
|
In 2020 and 2018, we excluded all options and awards from the calculations because we reported net losses in the periods, and the inclusion of such shares would have had an antidilutive effect.
|
|
|
|
|
|
|
|
|
|
|
|
| Year Ended December 31, |
| |||||||
|
| 2018 |
| 2017 |
| 2016 |
| |||
|
| (in thousands, except share and per share data) |
| |||||||
|
|
|
| (As Revised) |
| (As Revised) |
| |||
Basic |
|
|
|
|
|
|
|
|
|
|
Numerator: |
|
|
|
|
|
|
|
|
|
|
Net income (loss) attributable to common stockholders for basic net income (loss) per share |
| $ | (70,409) |
| $ | (38,486) |
| $ | 45,125 |
|
Denominator: |
|
|
|
|
|
|
|
|
|
|
Weighted-average common shares outstanding |
|
| 53,942,116 |
|
| 46,817,756 |
|
| 41,267,329 |
|
Basic net income (loss) per common share |
| $ | (1.31) |
| $ | (0.82) |
| $ | 1.09 |
|
Diluted |
|
|
|
|
|
|
|
|
|
|
Numerator: |
|
|
|
|
|
|
|
|
|
|
Net income (loss) attributable to common stockholders for diluted net income (loss) per share |
| $ | (70,409) |
| $ | (38,486) |
| $ | 45,125 |
|
Denominator: |
|
|
|
|
|
|
|
|
|
|
Weighted average number of common shares outstanding used in computing basic net income (loss) per common share |
|
| 53,942,116 |
|
| 46,817,756 |
|
| 41,267,329 |
|
Dilutive effect of employee stock options and ESPP |
|
| — |
|
| — |
|
| 1,121,538 |
|
Weighted-average number of common shares outstanding used in computing diluted net income (loss) per common share |
|
| 53,942,116 |
|
| 46,817,756 |
|
| 42,388,867 |
|
Diluted net income (loss) per common share |
| $ | (1.31) |
| $ | (0.82) |
| $ | 1.07 |
|
| | | | | | | | | | |
| | Year Ended December 31, |
| |||||||
| | 2020 | | 2019 | | 2018 |
| |||
| | (in thousands, except share and per share data) |
| |||||||
Basic |
| |
|
| |
|
| |
| |
Numerator: | | | | | | | | | | |
Net income (loss) attributable to common stockholders for basic net income (loss) per share | | $ | (69,333) | | $ | 26,875 | | $ | (70,409) | |
Denominator: | | | | | | | | | | |
Weighted-average common shares outstanding | | | 57,212,737 | |
| 56,531,439 | |
| 53,942,116 | |
Basic net income (loss) per common share | | $ | (1.21) | | $ | 0.48 | | $ | (1.31) | |
Diluted | | | | | | | | | | |
Numerator: | | | | | | | | | | |
Net income (loss) attributable to common stockholders for diluted net income (loss) per share | | $ | (69,333) | | $ | 26,875 | | $ | (70,409) | |
Denominator: | | | | | | | | | | |
Weighted average number of common shares outstanding used in computing basic net income (loss) per common share | | | 57,212,737 | |
| 56,531,439 | |
| 53,942,116 | |
Dilutive effect of employee stock options and ESPP | | | — | |
| 1,936,441 | |
| — | |
Weighted-average number of common shares outstanding used in computing diluted net income (loss) per common share | | | 57,212,737 | |
| 58,467,880 | |
| 53,942,116 | |
Diluted net income (loss) per common share | | $ | (1.21) | | $ | 0.46 | | $ | (1.31) | |
Segment Reporting
The Company determines its segment reporting based upon the way the business is organized for making operating decisions and assessing performance. The Company has only one1 operating segment related to the development of pharmaceutical products.products.
2. Comprehensive Income (Loss)
Comprehensive income (loss) is comprised of net income (loss) and other comprehensive income (loss). For the years ended December 31, 20182020 and 2017,2019, the only component of other comprehensive lossincome (loss) is net unrealized lossesgains on marketable debt securities. There were no material reclassifications out of accumulated other comprehensive loss during the year ended December 31, 2018.2020.
9490
3. Marketable Securities
The Company’s marketable debt securities held as of December 31, 20182020 and 20172019 are summarized below:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| December 31, 2018 | ||||||||||
|
|
|
|
| Gross |
| Gross |
|
|
| ||
|
| Amortized |
| Unrealized |
| Unrealized |
|
| ||||
|
| Cost |
| Gains |
| Losses |
| Fair Value | ||||
(in thousands) |
|
|
|
|
|
|
|
|
|
|
|
|
Money Market Funds |
| $ | 18,270 |
| $ | — |
| $ | — |
| $ | 18,270 |
Corporate Securities |
|
| 105,311 |
|
| 1 |
|
| (345) |
|
| 104,967 |
Government Securities |
|
| 399,873 |
|
| 187 |
|
| (804) |
|
| 399,256 |
|
| $ | 523,454 |
| $ | 188 |
| $ | (1,149) |
| $ | 522,493 |
|
|
|
|
|
|
|
|
|
|
|
|
|
Reported as |
|
|
|
|
|
|
|
|
|
|
|
|
Cash and cash equivalents |
|
|
|
|
|
|
|
|
|
| $ | 18,270 |
Marketable securities |
|
|
|
|
|
|
|
|
|
|
| 504,223 |
Total investments |
|
|
|
|
|
|
|
|
|
| $ | 522,493 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| December 31, 2017 | ||||||||||
|
|
|
|
| Gross |
| Gross |
|
|
| ||
|
| Amortized |
| Unrealized |
| Unrealized |
|
| ||||
|
| Cost |
| Gains |
| Losses |
| Fair Value | ||||
(in thousands) |
|
|
|
|
|
|
|
|
|
|
|
|
Money Market Funds |
| $ | 5,175 |
| $ | — |
| $ | — |
| $ | 5,175 |
Corporate Securities |
|
| 123,860 |
|
| — |
|
| (590) |
|
| 123,270 |
Government Securities |
|
| 224,739 |
|
| — |
|
| (1,209) |
|
| 223,530 |
|
| $ | 353,774 |
| $ | — |
| $ | (1,799) |
| $ | 351,975 |
|
|
|
|
|
|
|
|
|
|
|
|
|
Reported as |
|
|
|
|
|
|
|
|
|
|
|
|
Cash and cash equivalents |
|
|
|
|
|
|
|
|
|
| $ | 5,175 |
Marketable securities |
|
|
|
|
|
|
|
|
|
|
| 346,800 |
Total investments |
|
|
|
|
|
|
|
|
|
| $ | 351,975 |
| | | | | | | | | | | | |
| | December 31, 2020 | ||||||||||
| | | | | Gross | | Gross | | | | ||
|
| Amortized |
| Unrealized | | Unrealized |
| | ||||
| | Cost | | Gains | | Losses | | Fair Value | ||||
(in thousands) | | | | | | | | | | | | |
Money Market Funds | | $ | 158,937 | | $ | — | | $ | — | | $ | 158,937 |
Corporate Securities | | | 119,782 | | | 57 | | | (6) | | | 119,833 |
Government Securities | | | 315,319 | | | 37 | | | (3) | | | 315,353 |
| | $ | 594,038 | | $ | 94 | | $ | (9) | | $ | 594,123 |
| | | | | | | | | | | | |
Reported as | | | | | | | | | | | | |
Cash and cash equivalents | | | | | | | | | | | $ | 158,937 |
Marketable securities | | | | | | | | | | | | 435,186 |
Total investments | | | | | | | | | | | $ | 594,123 |
| | | | | | | | | | | | |
| | | | | | | | | | | | |
| | December 31, 2019 | ||||||||||
| | | | | Gross | | Gross | | | | ||
|
| Amortized |
| Unrealized | | Unrealized |
| | ||||
| | Cost | | Gains | | Losses | | Fair Value | ||||
(in thousands) | | | | | | | | | | | | |
Money Market Funds | | $ | 32,009 | | $ | — | | $ | — | | $ | 32,009 |
Corporate Securities | | | 281,586 | | | 195 | | | (30) | | | 281,751 |
Government Securities | | | 268,239 | | | 1,006 | | | — | | | 269,245 |
| | $ | 581,834 | | $ | 1,201 | | $ | (30) | | $ | 583,005 |
| | | | | | | | | | | | |
Reported as | | | | | | | | | | | | |
Cash and cash equivalents | | | | | | | | | | | $ | 32,009 |
Marketable securities | | | | | | | | | | | | 550,996 |
Total investments | | | | | | | | | | | $ | 583,005 |
The maturities of the Company’s marketable debt securities as of December 31, 20182020 are as follows:
|
|
|
|
|
|
|
|
| Amortized |
| Estimated | ||
|
| Cost |
| Fair Value | ||
(in thousands) |
|
|
|
|
|
|
Mature in one year or less |
| $ | 269,092 |
| $ | 268,115 |
Mature after one year through five years |
|
| 236,092 |
|
| 236,108 |
|
| $ | 505,184 |
| $ | 504,223 |
| | | | | | |
| | Amortized |
| Estimated | ||
| | Cost | | Fair Value | ||
(in thousands) | | | | | | |
Mature in one year or less | | $ | 434,071 | | $ | 434,156 |
Mature after one year through five years | | | 1,030 | | | 1,030 |
| | $ | 435,101 | | $ | 435,186 |
9591
The unrealized losses on available-for-sale investments and their related fair values as of December 31, 20182020 and 20172019 are as follows:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| December 31, 2018 | ||||||||||
|
| Less than 12 months |
| 12 months or greater | ||||||||
|
|
| Fair value |
|
| Unrealized losses |
|
| Fair value |
|
| Unrealized gain (losses) |
(in thousands) |
|
|
|
|
|
|
|
|
|
|
|
|
Corporate Securities |
| $ | 84,770 |
| $ | (310) |
| $ | 20,198 |
| $ | (34) |
Government Securities |
|
| 183,345 |
|
| (667) |
|
| 215,910 |
|
| 50 |
|
| $ | 268,115 |
| $ | (977) |
| $ | 236,108 |
| $ | 16 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| December 31, 2017 | ||||||||||
|
| Less than 12 months |
| 12 months or greater | ||||||||
|
|
| Fair value |
|
| Unrealized losses |
|
| Fair value |
|
| Unrealized losses |
(in thousands) |
|
|
|
|
|
|
|
|
|
|
|
|
Corporate Securities |
| $ | 79,290 |
| $ | (137) |
| $ | 43,980 |
| $ | (453) |
Government Securities |
|
| 128,313 |
|
| (461) |
|
| 95,217 |
|
| (748) |
|
| $ | 207,603 |
| $ | (598) |
| $ | 139,197 |
| $ | (1,201) |
| | | | | | | | | | | | |
| | December 31, 2020 | ||||||||||
| | Less than 12 months | | 12 months or greater | ||||||||
| | | Fair value | | | Unrealized losses | | | Fair value | | | Unrealized losses |
(in thousands) | | | | | | | | | | | | |
Corporate Securities | | $ | 15,843 | | $ | (6) | | $ | — | | $ | — |
Government Securities | | | 40,802 | | | (3) | | | — | | | — |
| | $ | 56,645 | | $ | (9) | | $ | — | | $ | — |
| | | | | | | | | | | | |
| | | | | | | | | | | | |
| | December 31, 2019 | ||||||||||
| | Less than 12 months | | 12 months or greater | ||||||||
| | | Fair value | | | Unrealized losses | | | Fair value | | | Unrealized losses |
(in thousands) | | | | | | | | | | | | |
Corporate Securities | | $ | 46,303 | | $ | (24) | | $ | 13,992 | | $ | (6) |
The unrealized losses from the listed securities are due to a change in the interest rate environment and not a change in the credit quality of the securities.
For the year ended December 31, 2020, the Company received shares of Aimmune common stock and MiRagen common stock in connection with the Aimmune and MiRagen Agreements (both as defined below). Aimmune common stock was redeemed for cash within the same year; MiRagen common stock is classified as equity securities with a readily determinable fair value at December 31, 2020. For the year ended December 31, 2020, the Company also received equity of a private company in connection with a licensing agreement. The Company elects measurement alternative to carry the investment at cost minus impairment, plus or minus changes resulting from observable price changes in orderly transactions for the identical or a similar investment of the same issuer. There has not been any impairment or observable price changes related to this investment. We did not hold any equity securities in our investment portfolio during the year ended December 31, 2019.
Net gains and losses during the year ended December 31, 2020 and 2019 consist of the following:
| | | | | | |
| | Year Ended December 31, | ||||
| | 2020 | | 2019 | ||
| | | ||||
Net gains recognized on equity securities | | $ | 105 | | $ | — |
Less: net gains recognized on equity securities redeemed | | | 801 | |
| — |
Unrealized losses recognized on equity securities | | $ | (696) | | $ | — |
4. Sale of Additional Common Stock
In March 2015, we completed the sale of 8,625,000 shares of common stock which included shares we issued pursuant to our underwriters’ exercise of their over-allotment option pursuant to a follow-on offering. We received net proceeds of $115.2 million, after underwriting discounts, commissions and estimated offering expenses.
In December 2016, we completed the sale of 5,272,750 shares of common stock which included shares we issued pursuant to our underwriters’ exercise of their over-allotment option pursuant to a follow-on financing. We received net proceeds of $119.3 million after underwriting discounts, commissions and offering expenses.
In March 2018, we completed the sale of 8,395,000 shares of commons stock which included shares we issued pursuant to our underwriters’ exercise of their over-allotment option pursuant to a follow-on financing. We received net proceeds of $245.5$245.5 million, after underwritersunderwriters’ discounts and offering expenses.
On September 19, 2016, we entered into an Equity Distribution Agreement (the Distribution Agreement) with Piper Jaffray & Co (Piper Jaffray) pursuant to which we may sell from time to time, at our option, up to an aggregate of $40 million of common stock through Piper Jaffray as sales agent. The issuance and sale of these shares by Xencor under the Distribution Agreement will be pursuant to our shelf registration statement on Form S-3 (File No.333-213700) declared effective by the SEC on October 5, 2016. We are not obligated sell any shares of common stock under the Distribution Agreement, and to date we have not sold any shares under the Distribution Agreement.
9692
5. Property and Equipment
Property and equipment consist of the following:
|
|
|
|
|
|
|
|
|
| December 31, |
| ||||
|
| 2018 |
| 2017 |
| ||
|
| (In thousands) |
| ||||
Computers, software and equipment |
| $ | 16,292 |
| $ | 10,874 |
|
Furniture and fixtures |
|
| 173 |
|
| 152 |
|
Leasehold and tenant improvements |
|
| 4,774 |
|
| 4,010 |
|
|
|
| 21,239 |
|
| 15,036 |
|
Less accumulated depreciation and amortization |
|
| (9,426) |
|
| (7,948) |
|
|
| $ | 11,813 |
| $ | 7,088 |
|
| | | | | | | |
| | December 31, |
| ||||
| | 2020 | | 2019 |
| ||
| | (in thousands) |
| ||||
Computers, software and equipment |
| $ | 31,229 |
| $ | 21,087 | |
Furniture and fixtures | | | 527 | |
| 492 | |
Leasehold and tenant improvements | | | 6,957 | |
| 6,831 | |
| | | 38,713 | |
| 28,410 | |
Less accumulated depreciation and amortization | |
| (17,031) | |
| (12,605) | |
| | $ | 21,682 | | $ | 15,805 | |
Depreciation and amortization expense related to property and equipment in 2020, 2019 and 2018 2017was $4.7 million, $3.4 million and 2016 was $2.4 million, $1.2 million and $0.7 million, respectively.
6. Income Taxes
Our effective tax rate differs from the statutory federal income tax rate, primarily as a result of the changes in valuation allowance. There was no0 provision for taxes for the years ended December 31, 2020 and December 31, 2018. The provision for income taxes for the year ended December 31, 2018. For2019 was $0.3 million, which represents the year ended December 31, 2017, the provision for income tax is a benefit of $0.5 million. Current tax expense of $1.0 million for the year ended December 31, 2016 represents federal andcurrent state alternative minimum tax.tax for the year.
A reconciliation of the federal statutory income tax to our effective income tax is as follows (in thousands):
|
|
|
|
|
|
|
|
|
|
|
|
| Year Ended |
| |||||||
|
| December 31, |
| |||||||
|
| 2018 |
| 2017 |
| 2016 |
| |||
|
|
|
|
| (Revised) |
| (Revised) |
| ||
Federal statutory income tax |
| $ | (14,795) |
| $ | (13,243) |
| $ | 15,680 |
|
State and local income taxes |
|
| (4,767) |
|
| (1,806) |
|
| 2,818 |
|
Research and development credit |
|
| (6,170) |
|
| (5,554) |
|
| (2,544) |
|
Stock based compensation |
|
| 444 |
|
| 2,709 |
|
| 733 |
|
Effect of the 2017 Tax Cut and Jobs Act |
|
| — |
|
| 19,596 |
|
| — |
|
Other |
|
| 414 |
|
| 720 |
|
| 1,008 |
|
Net change in valuation allowance |
|
| 24,874 |
|
| (2,885) |
|
| (16,695) |
|
Income tax provision (benefit) |
| $ | — |
| $ | (463) |
| $ | 1,000 |
|
| | | | | | | | | | |
| | Year Ended |
| |||||||
| | December 31, |
| |||||||
| | 2020 | | 2019 | | 2018 |
| |||
Federal statutory income tax |
| $ | (14,559) |
| $ | 5,709 |
| $ | (14,795) | |
State and local income taxes | | | (4,659) | |
| 2,549 | |
| (4,767) | |
Research and development credit | |
| (9,669) | |
| (6,747) | |
| (6,170) | |
Stock-based compensation | | | 529 | | | 1,927 | | | 444 | |
State credit | | | — | | | 1,725 | | | — | |
Other | | | 56 | |
| (301) | |
| 414 | |
Net change in valuation allowance | | | 28,302 | |
| (4,550) | |
| 24,874 | |
Income tax provision (benefit) | | $ | — | | $ | 312 | | $ | — | |
9793
The tax effect of temporary differences that give rise to a significant portion of the deferred tax assets and liabilities at December 31, 20182020 and 20172019 is presented below (in thousands):
|
|
|
|
|
|
|
|
|
| December 31, |
| ||||
|
| 2018 |
| 2017 |
| ||
|
|
|
|
| (Revised) |
| |
Deferred income tax assets |
|
|
|
|
|
|
|
Net operating loss carryforwards |
| $ | 49,889 |
| $ | 25,565 |
|
Research credits |
|
| 23,151 |
|
| 16,642 |
|
Depreciation |
|
| 207 |
|
| 437 |
|
Unrealized loss on securities |
|
| 269 |
|
| 504 |
|
Accrued compensation |
|
| 1,097 |
|
| 748 |
|
Deferred revenue |
|
| 11,222 |
|
| 16,820 |
|
State taxes |
|
| — |
|
| (2) |
|
Gross deferred income tax assets |
|
| 85,835 |
|
| 60,714 |
|
Valuation allowance |
|
| (82,537) |
|
| (57,663) |
|
Net deferred income tax assets |
|
| 3,298 |
|
| 3,051 |
|
Deferred income tax liabilities |
|
|
|
|
|
|
|
Patent costs |
|
| (3,142) |
|
| (2,873) |
|
Licensing costs |
|
| (125) |
|
| (142) |
|
Capitalized legal costs |
|
| (31) |
|
| (36) |
|
Gross deferred income tax liabilities |
|
| (3,298) |
|
| (3,051) |
|
Net deferred income tax asset |
| $ | — |
| $ | — |
|
| | | | | | | |
|
| December 31, |
| ||||
| | 2020 |
| 2019 | | ||
Deferred income tax assets | | | | | | | |
Net operating loss carryforwards | | $ | 56,182 | | $ | 36,891 | |
Research credits | | | 38,047 | |
| 28,415 | |
Depreciation | | | 137 | |
| 334 | |
Unrealized loss on securities | | | 195 | |
| — | |
Accrued compensation | | | 8,464 | |
| 4,788 | |
Deferred revenue | | | 11,925 | |
| 11,215 | |
State taxes | | | — | |
| 64 | |
Gross deferred income tax assets | | | 114,950 | |
| 81,707 | |
Valuation allowance | |
| (105,995) | |
| (77,389) | |
Net deferred income tax assets | | | 8,955 | |
| 4,318 | |
Deferred income tax liabilities | | | | | | | |
Patent costs | |
| (4,219) | |
| (3,736) | |
Equity investment | | | (4,497) | | | — | |
Licensing costs | |
| (194) | |
| (229) | |
Capitalized legal costs | |
| (21) | |
| (26) | |
Unrealized gain on securities | | | (24) | | | (327) | |
Gross deferred income tax liabilities | |
| (8,955) | |
| (4,318) | |
Net deferred income tax asset | | $ | — | | $ | — | |
The Tax Cuts and Jobs Act of 2017 (TCJA) was enacted in December 2017 and made substantial changes in the U.S. tax system. One of the changes was elimination of the AMT tax system for corporations and allowance of an income tax refund for AMT tax credit carryforwards as of December 31, 2017. We have reportedreceived an income tax receivablerefund of $1.6$0.8 million as ofand $0.8 million for each year ended December 31, 20182020 and 2017 to reflect the2019 for U.S. AMT credit carryforwards. We have net deferred tax assets relating primarily to net operating loss carryforwards we have available.and research and development tax credit carryforwards. Due to the uncertainty surrounding the realization of the benefits of our deferred tax assets in future tax periods, we have placed a valuation allowance against our deferred tax assets at December 31, 20182020 and 2017.2019. The Company recognizes valuation allowances to reduce deferred tax assets to the amount that is more likely than not to be realized. The Company’s net deferred income tax asset is not more likely than not to be realized due to the lack of sufficient sources of future taxable income and cumulative losses that have resulted over the years. During the year ended December 31, 2018,2020, the valuation allowance increased by $24.9$28.6 million. Upon analysis, there were changes in ownership under Section 382 of the Internal Revenue Code and related state provisions as a result of our sale of preferred stock and sale of common stock during 2013. Section 382 limits the amount of net operating losses and tax credit forwards that may be available after a change in ownership. The Company has adjusted its net operating loss and tax credit carryforwards to reflect the impact of the section 382 limitations. The Company’s tax returnsyears starting in 2016 through 2019 remain open to potential inspection forexamination by the years 2013U.S. and onwards for federal purposes and 2012 and onwards for state purposes.taxing authorities due to carryforwards of net operating losses.
As of December 31, 2018,2020, we had cumulative net operating loss carryforwards for federal and state income tax purposes of $191.1$213.6 million and $138.9$161.4 million, respectively, and available tax credit carryforwards of approximately $14.9$26.7 million for federal income tax purposes and $8.2$14.3 million for state income tax purposes, which can be carried forward to offset future taxable income, if any. The federal net operating loss carryforwards consistsconsist of $102.6$68.0 million of losses incurred prior to January 1, 2018, which are subject to carryforward limitations and which can be used to offset 100% of future taxable income and, $88.6$145.6 million of losses incurred after January 1, 2018, which canmay be used to offset up to 80% of taxable income in subsequent years.carried forward indefinitely.
Our federal net operating loss carryforwards expire starting in 2026, state net operating lossesloss carryforwards expire starting in 2032,2035, and federal tax credit carryforwards began to expire starting in 2019. A total of $0.03 million in federal tax credits expired in 2019, and an additional $0.3 million will expire over the next five years if not utilized. Utilization of theour net operating lossesloss and tax creditscredit carryforwards are subject to a substantial annual limitation under Section 382 of the Code due to the fact that we have experienced ownership changes which occurred.changes. As a result of these changes, provisions in the Internal Revenue Code of 1986 under Section 382 and similar state provisions may result in the expiration of certain of our net operating lossesloss and tax creditscredit carryforwards may expire before we can use them.
9894
7. Stock‑BasedStock-Based Compensation
Our Board of Directors and the requisite stockholders previously approved the 2010 Equity Incentive Plan (the 2010 Plan). In October 2013, our Board of Directors approved the 2013 Equity Incentive Plan (the 2013 Plan), and in November 2013 our stockholders approved the 2013 Plan. The 2013 Plan provides for the grant of incentive stock options, nonstatutory stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, performance stock awards, performance cash awards, and other stock awards. The 2013 Plan became effective as of December 3,2, 2013, the date of the pricing of the Company’s initial public offering. As of December 2, 2013, we suspended the 2010 Plan, and no0 additional awards may be granted under the 2010 Plan. Any shares of common stock covered by awards granted under the 2010 Plan that terminate after December 2, 2013 by expiration, forfeiture, cancellation or other means without the issuance of such shares will be added to the 2013 Plan reserve.
As of December 31, 2018,2020, the total number of shares of common stock available for issuance under the 2013 Plan was 9,581,833.11,479,096. Unless otherwise determined by the Board, beginning January 1, 2014, and continuing until the expiration of the 2013 Plan, the total number of shares of common stock available for issuance under the 2013 Plan will automatically increase annually on January 1 by 4% of the total number of issued and outstanding shares of common stock as of December 31 of the immediateimmediately preceding year. On January 1, 2018,2020, the total number of shares of common stock available for issuance under the 2013 Plan was automatically increased by 1,880,1001,138,046 shares, which number is included in the number of shares available for issuance above. As of December 31, 20182020, a total of 6,751,28710,572,839 options have been issuedgranted under the 2013 Plan.
During the year endedAs of December 31, 2018,2020, the Company has awarded 33,933 Restricted Stock Units (RSUs)453,787 RSUs to certain employees pursuant to the 2013 Plan. Vesting of these awards will be in three3 equal annual installments and is contingent on continued employment terms. The fair value of these awards is determined based on the intrinsic value of the stock on the date of grant and will be recognized as stock-based compensation expense over the requisite service period.
In November 2013, our Board of Directors and stockholders approved the 2013 Employee Stock Purchase Plan (ESPP), which became effective as of December 5, 2013. Under the ESPP our employees may elect to have between 1-15% of their compensation withheld to purchase shares of the Company’s common stock at a discount. The ESPP had an initial two-year term that includes four4 six-month purchase periods, and employee withholding amounts may be used to purchase Company stock during each six-month purchase period. The initial two-year term ended in December 2015 and pursuant to the provisions of the ESPP, the second two-year term began automatically upon the end of the initial term. The total number of shares that can be purchased with the withholding amounts are based on the lower of 85% of the Company’s common stock price at the initial offering date or 85% of the Company’s stock price at each purchase date.
We have reserved a total of 581,286 shares of common stock for issuance under the ESPP. Unless otherwise determined by our Board, beginning on January 1, 2014, and continuing until the expiration of the ESPP, the total number shares of common stock available for issuance under the ESPP will automatically increase annually on January 1 by the lesser of (i) 1% of the total number of issued and outstanding shares of common stock as of December 31 of the immediately preceding year, or (ii) 621,814 shares of common stock. On January 1, 2014, the total number of shares of common stock available for issuance under the ESPP was automatically increased by 313,545 shares, which number is included in the number of shares reserved for issuance above. Pursuant to approval by our board, there were no0 increases in the number of authorized shares in the ESPP in years from 2015 to 2018.2020. As of December 31, 2018,2020, we have issued a total of 349,716467,595 shares of common stock under the ESPP.
9995
Total employee, director and non‑employee stock‑basednon-employee stock-based compensation expense recognized was as follows:
|
|
|
|
|
|
|
|
|
|
|
|
| Year Ended |
| |||||||
|
| December 31, |
| |||||||
(In thousands) |
| 2018 |
| 2017 |
| 2016 |
| |||
General and administrative |
| $ | 7,699 |
| $ | 5,617 |
| $ | 3,592 |
|
Research and development |
|
| 12,849 |
|
| 8,034 |
|
| 4,256 |
|
|
| $ | 20,548 |
| $ | 13,651 |
| $ | 7,848 |
|
|
|
|
|
|
|
|
|
|
|
|
|
| Year Ended |
| |||||||
|
| December 31, |
| |||||||
(In thousands) |
| 2018 |
| 2017 |
| 2016 |
| |||
Stock options |
| $ | 19,537 |
| $ | 13,153 |
| $ | 7,470 |
|
ESPP |
|
| 744 |
|
| 498 |
|
| 378 |
|
Restricted stock units |
|
| 267 |
|
| — |
|
| — |
|
|
| $ | 20,548 |
| $ | 13,651 |
| $ | 7,848 |
|
| | | | | | | | | | |
| | Year Ended |
| |||||||
| | December 31, |
| |||||||
(in thousands) | | 2020 | | 2019 | | 2018 |
| |||
General and administrative |
| $ | 10,769 |
| $ | 8,854 |
| $ | 7,699 | |
Research and development | | | 20,850 | |
| 22,997 | |
| 12,849 | |
| | $ | 31,619 | | $ | 31,851 | | $ | 20,548 | |
| | | | | | | | | | |
| | Year Ended | | |||||||
| | December 31, | | |||||||
(in thousands) | | 2020 | | 2019 | | 2018 | | |||
Stock options |
| $ | 26,045 |
| $ | 30,502 |
| $ | 19,537 | |
ESPP | | | 804 | |
| 687 | |
| 744 | |
RSUs | | | 4,770 | |
| 662 | |
| 267 | |
| | $ | 31,619 | | $ | 31,851 | | $ | 20,548 | |
Information with respect to stock options outstanding is as follows:
|
|
|
|
|
|
|
|
|
|
|
|
| December 31, |
| |||||||
|
| 2018 |
| 2017 |
| 2016 |
| |||
Exercisable options |
|
| 3,058,659 |
|
| 2,558,941 |
|
| 1,743,765 |
|
Weighted average exercise price per share of exercisable options |
| $ | 15.12 |
| $ | 11.06 |
| $ | 8.87 |
|
Weighted average grant date fair value per share of options granted during the year |
| $ | 18.06 |
| $ | 16.92 |
| $ | 10.30 |
|
Options available for future grants |
|
| 3,576,574 |
|
| 3,394,691 |
|
| 2,943,216 |
|
Weighted average remaining contractual life |
|
| 7.51 |
|
| 7.62 |
|
| 7.82 |
|
| | | | | | | | | | |
|
| December 31, |
| |||||||
| | 2020 | | 2019 | | 2018 |
| |||
Exercisable options |
| | 4,668,179 |
| | 3,950,965 |
| | 3,058,659 | |
Weighted average exercise price per share of exercisable options | | $ | 21.75 | | $ | 17.79 | | $ | 15.12 | |
Weighted average grant date fair value per share of options granted during the year | | $ | 16.96 | | $ | 20.74 | | $ | 18.06 | |
Options available for future grants | |
| 3,346,092 | |
| 3,975,160 | |
| 3,576,574 | |
Weighted average remaining contractual life | |
| 7.00 | |
| 7.32 | |
| 7.51 | |
The following table summarizes stock option activity for the years ended December 31, 20182020 and 2017:2019:
| | | | | | | | | | | |
|
| |
| | |
| Weighted- |
| | |
|
| | | | Weighted- | | Average | | | |
| |
| | | | Average | | Remaining | | | |
| |
| | | | Exercise | | Contractual | | Aggregate |
| ||
| | Number of | | Price | | Term | | Intrinsic Value |
| ||
| | Shares | | (Per Share)(1) | | (in years) | | (in thousands)(2) |
| ||
Balances at December 31, 2018 |
| 5,966,928 | |
| 19.71 |
| 7.51 | | $ | 99,273 | |
Options granted |
| 2,142,228 | | | 35.80 | | | | | | |
Options forfeited |
| (390,950) | | | 32.23 | | | | | | |
Options exercised(3) |
| (543,887) | | | 17.04 | | | | | | |
Balances at December 31, 2019 |
| 7,174,319 | |
| 24.03 |
| 7.32 | | $ | 79,116 | |
Options granted |
| 1,679,324 | | | 33.08 | | | | | | |
Options forfeited |
| (243,384) | | | 32.93 | | | | | | |
Options exercised(3) |
| (858,470) | | | 19.36 | | | | | | |
Balances at December 31, 2020 |
| 7,751,789 | | $ | 26.23 | | 7.00 | | $ | 134,941 | |
As of December 31, 2020 | | | | | | | | | | | |
Options vested and expected to vest |
| 7,751,789 | | $ | 26.23 |
| 7.00 | | $ | 134,941 | |
Exercisable |
| 4,668,179 | | $ | 21.75 |
| 5.91 | | $ | 102,120 | |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Weighted- |
|
|
|
|
|
|
|
| Weighted- |
| Average |
|
|
|
| |
|
|
|
| Average |
| Remaining |
|
|
|
| |
|
|
|
| Exercise |
| Contractual |
| Aggregate |
| ||
|
| Number of |
| Price |
| Term |
| Intrinsic Value |
| ||
|
| Shares |
| (Per Share)(1) |
| (in years) |
| (in thousands)(2) |
| ||
Balances at December 31, 2016 |
| 4,045,801 |
|
| 11.95 |
| 7.82 |
| $ | 58,131 |
|
Options granted |
| 1,511,100 |
|
| 22.61 |
|
|
|
|
|
|
Options forfeited |
| (96,856) |
|
| 17.08 |
|
|
|
|
|
|
Options expired |
| (3,000) |
|
| 21.99 |
|
|
|
|
|
|
Options exercised(3) |
| (363,603) |
|
| 7.69 |
|
|
|
|
|
|
Balances at December 31, 2017 |
| 5,093,442 |
|
| 15.32 |
| 7.62 |
| $ | 35,495 |
|
Options granted |
| 1,805,937 |
|
| 27.43 |
|
|
|
|
|
|
Options forfeited |
| (107,720) |
|
| 21.66 |
|
|
|
|
|
|
Options exercised(3) |
| (824,731) |
|
| 9.24 |
|
|
|
|
|
|
Balances at December 31, 2018 |
| 5,966,928 |
| $ | 19.71 |
| 7.51 |
| $ | 99,273 |
|
As of December 31, 2018 |
|
|
|
|
|
|
|
|
|
|
|
Options vested and expected to vest |
| 5,966,928 |
| $ | 19.71 |
| 7.51 |
| $ | 99,273 |
|
Exercisable |
| 3,058,659 |
| $ | 15.12 |
| 6.42 |
| $ | 64,417 |
|
| (1) |
| The weighted average exercise price per share is determined using exercise price per share for stock options. |
| (2) |
| The aggregate intrinsic value is calculated as the difference between the exercise price of the option and the fair value of our common stock for |
100
| (3) |
| The total intrinsic value of stock options exercised was |
96
The stock options outstanding and exercisable by exercise price at December 31, 20182020 are as follows:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Stock Options Outstanding |
| Stock Options Exercisable |
| ||||||||||
|
|
|
| Weighted- |
|
|
|
|
|
|
|
|
|
|
|
|
| Average |
|
|
|
|
|
|
|
|
|
|
|
|
| Remaining |
| Weighted- |
|
|
| Weighted- |
| ||
Range of |
|
|
| Contractual |
| Average |
|
|
| Average |
| ||
Exercise |
| Number of |
| Term |
| Exercise Price |
| Number of |
| Exercise Price |
| ||
Prices |
| Shares |
| (in years) |
| Per Share |
| Shares |
| Per Share |
| ||
$0.59 – $4.25 |
| 291,433 |
| 4.49 |
| $ | 3.63 |
| 291,433 |
| $ | 3.63 |
|
$9.78 – $14.75 |
| 1,560,249 |
| 6.39 |
| $ | 12.10 |
| 1,281,242 |
| $ | 11.97 |
|
$14.77 – $22.18 |
| 852,138 |
| 6.62 |
| $ | 17.00 |
| 706,562 |
| $ | 16.35 |
|
$22.20 – $33.78 |
| 2,929,571 |
| 8.42 |
| $ | 23.92 |
| 760,672 |
| $ | 23.08 |
|
$34.56 – $43.16 |
| 333,537 |
| 9.68 |
| $ | 39.26 |
| 18,750 |
| $ | 38.93 |
|
|
| 5,966,928 |
| 7.51 |
| $ | 19.71 |
| 3,058,659 |
| $ | 15.12 |
|
| | | | | | | | | | | | | |
Stock Options Outstanding | | Stock Options Exercisable |
| ||||||||||
| | | | Weighted- | | | | | | | | |
|
| | | | Average | | | | | | | | |
|
|
| |
| Remaining |
| Weighted- |
| |
| Weighted- |
| ||
Range of | | | | Contractual | | Average | | | | Average |
| ||
Exercise | | Number of | | Term | | Exercise Price | | Number of | | Exercise Price |
| ||
Prices | | Shares | | (in years) | | Per Share | | Shares | | Per Share |
| ||
$4.25 – $10.28 |
| 153,038 |
| 2.68 | | $ | 4.29 |
| 153,038 | | $ | 4.29 | |
$10.52 – $15.78 |
| 1,639,702 |
| 4.30 | | $ | 13.10 |
| 1,638,717 | | $ | 13.10 | |
$15.91 – $23.87 |
| 1,980,437 |
| 6.53 | | $ | 22.75 |
| 1,654,609 | | $ | 22.67 | |
$23.96 – $35.94 | | 2,330,771 | | 8.65 | | $ | 31.80 | | 530,056 | | $ | 30.12 | |
$35.99 – $53.99 | | 1,647,841 | | 8.34 | | $ | 37.63 | | 691,759 | | $ | 37.51 | |
|
| 7,751,789 |
| 7.00 | | $ | 26.23 |
| 4,668,179 | | $ | 21.75 | |
We estimated the fair value of employee and non‑employeenon-employee awards using the Black‑ScholesBlack-Scholes valuation model. The fair value of employee stock options is being amortized on a straight‑linestraight-line basis over the requisite service period of the awards. Management estimates the probability of non‑employeenon-employee awards being vested based upon an evaluation of the non‑employeenon-employee achieving their specific performance goals.
Options granted after our initial public offering are issued at the fair market value of our stock on the date of grant.
The fair value of employee stock options was estimated using the following weighted average assumptions for the years ended December 31, 2018, 20172020, 2019 and 2016:2018:
|
|
|
|
|
|
|
|
|
|
|
|
| Options |
| |||||||
|
| 2018 |
| 2017 |
| 2016 |
| |||
Common stock fair value per share |
| $ | 21.80 - 43.16 |
| $ | 19.61 - 25.67 |
| $ | 11.50 - 26.76 |
|
Expected volatility |
|
| 70.97% - 73.10% |
|
| 77.42% - 96.73% |
|
| 75.77% - 90.83% |
|
Risk-free interest rate |
|
| 2.29% - 3.10% |
|
| 0.96% - 2.37% |
|
| 1.03% - 2.18% |
|
Expected dividend yield |
|
| — |
|
| — |
|
| — |
|
Expected term (in years) |
|
| 5.23 - 6.08 |
|
| 5.23 - 6.08 |
|
| 5.23 - 6.08 |
|
|
|
|
|
|
|
|
| ||||||||||
|
| ESPP |
| ||||||||||||||
|
| 2018 |
| 2017 |
| 2016 |
| ||||||||||
Expected term (years) |
| 0.5 - 2.0 |
| 0.5 - 2.0 |
| 0.5 - 2.0 |
| ||||||||||
| | | | | | | | | | | |||||||
| | Options | | ||||||||||||||
|
| 2020 |
| 2019 |
| 2018 |
| ||||||||||
Common stock fair value per share | | $ | 20.69 - 45.91 | | $ | 29.96 - 44.19 | | $ | 21.80 - 43.16 | | |||||||
Expected volatility |
| 57.0% - 71.4% |
| 67.8% - 79.8% |
| 67.8% - 79.8% |
| |
| 52.93% - 58.95% | |
| 60.67% - 61.33% | |
| 70.97% - 73.10% | |
Risk-free interest rate |
| 1.47% - 2.70% |
| 0.47% - 1.80% |
| 0.47% - 0.93% |
| |
| 0.29% - 1.71% | |
| 1.37% - 2.60% | |
| 2.29% - 3.10% | |
Expected dividend yield |
| — |
| — |
| — |
| |
| — | |
| — | |
| — | |
Expected term (in years) | |
| 5.23 - 7.65 | |
| 5.23 - 6.59 | |
| 5.23 - 6.08 | | |||||||
| | | | | | | |
| | ESPP | | ||||
|
| 2020 |
| 2019 |
| 2018 | |
Expected term (years) |
| 0.5 - 2.0 |
| 0.5 - 2.0 |
| 0.5 - 2.0 | |
Expected volatility | | 50.77% - 66.37% | | 50.77% - 71.37% | | 57.04% - 71.37% | |
Risk-free interest rate |
| 0.09% - 1.65% | | 1.47% - 2.70% | | 1.47% - 2.70% | |
Expected dividend yield | | — | | — | | — | |
The expected term of stock options represents the average period the stock options are expected to remain outstanding. The expected stock price volatility for our stock options for the years ended December 31, 2020 and 2019 was determined using a blended volatility by examining the historical volatility for industry peer companies and the volatility of our stock from the effective date that our shares were publicly traded on a national stock exchange. For the year ended December 31, 2018, 2017 and 2016expected stock volatility was determined by examining the historical volatilities for industry peers and adjusting for differences in our life cycle and financing leverage. Industry peers consist of several public companies in the biopharmaceutical industry.
We determined the average expected life of stock options based on the simplified method because our common stock has not been publicly traded for an extendedanticipated time period between the measurement date and we do not have a track record of our stock being traded on the public markets for sufficient time to establishexercise date by examining the volatility of our stock.
101
option holders’ past exercise patterns.
The risk‑freerisk-free interest rate assumption is based on the U.S. Treasury instruments, whosefor which the term was consistent with the expected term of our stock options.
97
The expected dividend assumption is based on our history and expectation of dividend payouts. We have not paid dividends and did not have any dividend payout at December 31, 2020.
The following table summarizes restricted stock unitsRSU activity for the years ended December 31, 2018:2020:
|
|
|
|
|
|
|
|
|
| Weighted- | |
|
|
|
| Average | |
|
|
|
| Grant Date | |
|
| Number of |
| Fair Value | |
|
| Shares |
| (Per Unit) | |
Unvested at December 31, 2017 |
| — |
|
| — |
Granted |
| 33,933 |
| $ | 27.64 |
Vested |
| — |
|
| — |
Forfeited |
| — |
|
| — |
Unvested at December 31, 2018 |
| 33,933 |
| $ | 27.64 |
| | | | | |
| | | | Weighted- | |
| | | | Average | |
| | | | Grant Date | |
| | Number of | | Fair Value | |
| | Shares | | (Per Unit) | |
Unvested at December 31, 2018 |
| 33,933 | | $ | 27.64 |
Granted |
| 71,566 | | | 36.68 |
Vested |
| (11,311) | | | 27.64 |
Forfeited | | (4,182) | | | 31.12 |
Unvested at December 31, 2019 |
| 90,006 | | $ | 34.66 |
Granted |
| 348,288 | | | 32.51 |
Vested |
| (62,355) | | | 32.61 |
Forfeited | | (17,114) | | | 32.33 |
Unvested at December 31, 2020 |
| 358,825 | | $ | 33.04 |
As of December 31, 20182020 and 2017,2019, the unamortized compensation expense related to unvested stock options was $42.8$48.9 million and $30.7$51.1 million, respectively. The remaining unamortized compensation expense will be recognized over the next 2.712.54 years. At December 31, 20182020 and 2017,2019, the unamortized compensation expense was $0.8$0.9 million and $1.1$1.4 million respectively under our ESPP. The remaining unamortized expense will be recognized over the next 11.2 months.0.94 years. At December 31, 2018,2020 and 2019, the unamortized compensation expense related to unvested restricted stock units was $0.7$8.5 million whichand $2.5 million, respectively. The remaining unamortized compensation expense will be recognized over the next 2.152.13 years.
8. Commitments and ContingenciesLeases
Operating leases
The Company leases office and laboratory space in Monrovia, CA throughunder a lease that expired in June 2020.In April 2020 and in September 2020, the Company entered into amendments to the lease to extend the term of the lease under the original terms through October 2020. In November 2020, the Company entered into an amended lease for the space, which includes a 62-month term with an option to renew for an additional five years at then market rates.InJuly 2017, the Company entered into an amended lease agreement for additional space in the same building. The amendedbuilding with a lease has a 64-month termthat continues through September 2022, also with an option to renew for an additional five years. The Company assesses that it is likely to exercise both options of the lease terms for the original space were not amended.term extensions.
The Company also leasesleased office space in San Diego, CA through June 2020. In June 2017, the Company entered into a new lease agreement for an additional office space. The new lease has a 61-month term beginning from the date of occupancy and includesJuly 2020 which included an option to renew for an additional five years. AtThe lease expired and the Company did not exercise its option to extend the lease.
The Company leases additional office space in San Diego, CA through August 2022, with an option to extend for an additional five years. The Company assesses that it is unlikely to exercise the option to extend the lease term.
The Company’s lease agreements do not contain any residual value guarantees or restrictive covenants. As of December 31, 20182020, the future minimum lease payments underCompany did not have additional operating leases that have not yet commenced.
98
The following table reconciles the undiscounted cash flows for the operating leases were as follows:at December 31, 2020 to the operating lease liabilities recorded on the balance sheet (in thousands):
|
|
|
| |||
|
| Operating | ||||
| | | | |||
Years ending December 31, |
| Leases | | | ||
2019 |
| $ | 2,752 | |||
2020 |
|
| 2,404 | |||
2021 |
|
| 1,980 | | $ | 2,429 |
2022 |
|
| 1,406 | | | 2,269 |
2023 |
|
| — | | | 1,415 |
2024 | | | 1,436 | |||
2025 | | | 1,396 | |||
Thereafter |
|
| — | | | 5,342 |
Total undiscounted lease payments | | | 14,287 | |||
Less: Imputed interest | | | (2,659) | |||
Present value of lease payments | | $ | 11,628 | |||
| | | | |||
Lease liabilities - short-term | | $ | 1,889 | |||
Lease liabilities - long-term | | | 9,739 | |||
Total lease liabilities | | $ | 11,628 | |||
Rent expenses
The following table summarizes lease costs and cash disclosures for the years ended December 31, 2020 and 2019 (in thousands):
| | | | | | |
| | Year Ended | ||||
| | December 31, | ||||
| | 2020 |
| 2019 | ||
| | | | | | |
Operating lease cost | | $ | 2,503 | | $ | 2,596 |
Variable lease cost | | | 150 | | | 80 |
Total lease costs | | $ | 2,653 | | $ | 2,676 |
| | | | | | |
Cash paid for amounts included in | | | | | | |
the measurement of lease liabilities | | $ | 2,233 | | $ | 1,929 |
Rent expense for the year ended December 31, 2018 2017was $2.5 million.
The 2020 lease amendments to the Monrovia, CA lease are lease modifications. Non-cash activities involving right of use assets related to the lease modification were $3.1 million.
At December 31, 2020 and 20162019, the weighted-average remaining lease terms for operating leases were $2.5 million, $1.7 million,7.4 years and $0.6 million, respectively.5.5 years, respectively, and the weighted average discount rates for operating leases were both 5.5%.
9. Commitments and Contingencies
Contingencies
From time to time, the Company may be subject to various litigation and related matters arising in the ordinary course of business. The Company does not believe it is currently subject to any material matters where there is at least a reasonable possibility that a material loss may be incurred.
10299
On March 3, 2015, a verified class action complaint, captioned DePinto v. John S. Stafford, et al., C.A. No. 10742, was filed in the Court of Chancery of the State of Delaware against certain of the Company's current and former directors alleging cause of action for Breach of Fiduciary Duty and Invalidity of Director and Stockholder Consents and that the defendants breached their fiduciary duties in the course of approving a series of transactions. The complaint related to a financial recapitalization of the Company and certain related transactions that the Company completed in 2013.
On September 27, 2016, the parties engaged in voluntary mediation and agreed to settle the complaint’s outstanding claims for a total payment of $2.375 million to the class certified by the Delaware Court of Chancery. The settlement was reached without any party admitting wrongdoing. Under the terms of the settlement, no payment shall be made to the plaintiffs by the Company or any of the defendants in the lawsuit other than payments covered by the Company’s insurance.
On April 4, 2017, the Delaware Court of Chancery approved the settlement between the parties. On May 1, 2017, the Company’s insurance carriers fully funded the settlement account.
We recognized legal costs related to the litigation as incurred and offset any insurance proceeds when approved and issued. For the year ended December 31, 2017 no amount of loss related to the settlement has been accrued. At December 31, 2016, we reported the outstanding settlement amount of $2.355 million as a payable and reflected a receivable of the same amount for the insurance coverage. This amount was paid by the insurance carrier on our behalf in May 2017.
We are obligated to make future payments to third parties under in‑licensein-license agreements, including sublicense fees, royalties, and payments that become due and payable on the achievement of certain development and commercialization milestones. As the amount and timing of sublicense fees and the achievement and timing of these milestones are not probable and estimable, such commitments have not been included on our balance sheet. We have also entered into agreements with third party vendors which will require us to make future payments upon the delivery of goods and services in future periods.
Guarantees
In the normal course of business, we indemnify certain employees and other parties, such as collaboration partners and other parties that perform certain work on behalf of, or for the Company or take licenses to our technologies. We have agreed to hold these parties harmless against losses arising from our breach of representations or covenants, intellectual property infringement or other claims made against these parties in performance of their work with us.
These agreements typically limit the time within which the party may seek indemnification by us and the amount of the claim. It is not possible to prospectively determine the maximum potential amount of liability under these indemnification agreements since we have not had any prior indemnification claims on which to base the calculation. Further, each potential claim would be based on the unique facts and circumstances of the claim and the particular provisions of each agreement. We are not aware of any potential claims and we did not record a liability as of December 31, 20182020 and 2017.2019.
9.10. Collaboration and Licensing Agreements
Following is a summary description of the material revenue arrangements, including arrangements that generated revenue in the period ended December 31, 2018, 2017,2020, 2019, and 2016.2018. The revenue reported for each agreement has been adjusted to reflect the adoption of ASC 606 for each period presented.
103
NovartisJanssen Biotech, Inc.
In June 2016,November 2020, the Company entered into a Collaboration and License Agreement (Novartis(the Janssen Agreement) with Novartis InstitutesJanssen Biotech, Inc. (Janssen) pursuant to which Xencor and Janssen will conduct research and development activities to discover novel CD28 bispecific antibodies for BioMedical Research, Inc. (Novartis),the treatment of prostate cancer. Janssen and Xencor will conduct joint research activities for up to a three-year period to discover XmAb bispecific antibodies against CD28 and against an undisclosed prostate tumor-target with Janssen maintaining exclusive worldwide rights to develop and commercialize bispecific and other Fc engineered antibody drug candidates usingLicensed Products identified from the Company’s proprietary XmAb® technologies and drug candidates. Pursuant to the Novartis Agreement:
|
|
|
|
|
|
The Company received a non-refundable upfront payment under the Novartis Agreement of $150 million in July 2016 and is eligible to receive up to $2.1 billion in future development, regulatory and sales milestones in total for all programs that could be developed under the Novartis Agreement. In December 2018, Novartis notified the Company it was terminating its rights with respect to the XmAb13676 program, which will be effective June 2019. Under the Agreement, Novartis is responsible to fund its share of XmAb13676 development costs through June 2020.research activities.
Under the Novartis Agreement, the Company granted Novartis a worldwide co-exclusive license with the Company to research, develop and manufacture XmAb14045. The Company also granted Novartis an exclusive license to commercialize XmAb14045 in all worldwide territories outside the U.S.
The Company and Novartis will co-develop XmAb14045 worldwide and share development costs. The Company may elect to opt-out of the development of XmAb14045 by providing notice to Novartis. If the Company elects to opt-out, Novartis will receive the Company’s U.S. rights to XmAb14045 and the Company will receive low double-digit royalties on U.S. net sales in addition to the royalties on net sales outside the U.S.
Pursuant to the NovartisJanssen Agreement, the Company will conduct research activities and apply its bispecific Fc technology to up to four target pair antibodies selected, if available for exclusive license to Novartis and not subject to a Company internal program. The Company will apply its bispecific technology to generate bispecific antibody candidates from starting target pair antibodiestargeting prostate cancer provided by Novartis for eachJanssen. Upon completion of the four Global Discovery Programs and return the bispecific productresearch activities Janssen will have a candidate selection option to Novartisadvance an identified candidate for further testing, development and commercialization. Novartis has the rightThe activities will be conducted under a research plan agreed to substitute up to four of the original selected target pair antibodies during the research term provided that Novartis has not filed and received acceptance for an Investigational New Drug Application (IND) with the Company provided bispecific candidate. The research term is five years from the date of the Novartis Agreement.
We completed delivery of a Global Discovery Program in 2017 and delivery of a second Global Discovery Program in 2018.
Novartisby both parties. Janssen will assume full responsibility for development and commercialization of each product candidate under each of the Global Discovery Programs.
UnderCD28 bispecific antibody candidate. Pursuant to the NovartisJanssen Agreement, the Company hasreceived an upfront payment of $50.0 million and is eligible to receive up to $662.5 million in milestones which include $161.9 million in development milestones, $240.6 million in regulatory milestones and $260.0 million in sales milestones. If commercialized, the Company is eligible to receive royalties on net sales that range from the high-single to low-double digit percentages.
Pursuant to the Janssen Agreement, upon development of a bispecific candidate by Janssen through proof of concept, we have the right to participateopt-in to fund 20% of development costs and to perform 30% of detailing efforts in the U.S. If we exercise this right, we will be eligible to receive tiered royalties in the low-double digit to mid-teen percentage range.
We evaluated the Janssen Agreement under ASC 606 and identified the performance obligation under the Agreement to be delivery of CD28 bispecific antibodies to Janssen from the research activities outlined in the research
100
plan. The Company determined that the license to the bispecific antibodies is not a separate performance obligation because it is not capable of being distinct, the license to the antibodies cannot be separated from the underlying antibodies.
Janssen will benefit from delivery of the bispecific antibodies upon completion of the research activities.
The Company determined that the transaction price of the Janssen Agreement at inception was $50.0 million consisting of the upfront payment. The potential milestones are not included in the transaction price as these are contingent on future events and the Company would not recognize these in revenue until it is not probable that these would not result in significant reversal of revenue amounts in future periods. The candidate selection option payment is substantive and is a separate performance obligation. The Company will re-assess the transaction price at each reporting period and when event outcomes are resolved or changes in circumstances occur.
The Company allocated the transaction price to the single performance obligation, delivery of CD28 bispecific antibodies to Janssen.
The Company will recognize the $50.0 million transaction price as it satisfies its performance obligation to deliver CD28 bispecific antibodies to Janssen. The Company will recognize revenue related to the performance obligation over the expected period of time to complete and deliver the CD28 bispecific antibodies to Janssen using the expected input method which considers an estimate of the Company’s efforts to complete the research activities outlined in the Janssen Agreement.
NaN revenue was recognized under this arrangement for the year ended December 31, 2020, and there is $50.0 million in deferred revenue as of December 31, 2020 related to our obligation to complete research activities and deliver CD28 bispecific antibodies under the Janssen Agreement.
Aimmune Therapeutics, Inc.
On February 4, 2020, the Company entered into a License, Development and Commercialization Agreement (the Aimmune Agreement) with Aimmune Therapeutics, Inc. (Aimmune) pursuant to which the Company granted Aimmune an exclusive worldwide license to XmAb7195, which was renamed AIMab7195. Under the Aimmune Agreement, Aimmune will be responsible for all further development and commercialization activities for XmAb7195. The Company received an upfront payment of one$5.0 million and 156,238 shares of Aimmune common stock with an aggregate value of $4.6 million on the Global Discovery Programs prior to filing an IND forclosing date. Under the Global Discovery Program. IfAimmune Agreement, the Company electsis also eligible to participatereceive up to $385.0 million in milestones, which include $22.0 million in development it will assume responsibility for 25% of the worldwide development costs for the programmilestones, $53.0 million in regulatory milestones and 50% of commercialization costs$310.0 million in sales milestones, and will receive 50% of the U.S. profitstiered royalties on net sales of the product.
104
approved products from high-single to mid-teen percentage range.
Under the NovartisAimmune Agreement, Aimmune received exclusive worldwide rights to manufacture, develop and commercialize XmAb7195. They also received the Company also granted Novartis a non-exclusiverights to all data, information and research licensematerials related to use certain of the Company’s Fc technologies, specifically Cytotoxic, Xtend and Immune Inhibitor, to research, develop, commercialize and manufacture antibodies against up to ten targets selected by Novartis, if available for non-exclusive license and not subject to a Company internalXmAb7195 program. Novartis will assume all research, development and commercialization costs for products that are developed from application of the Fc technologies.
The Company evaluated the NovartisAimmune Agreement under the new revenue recognition standard ASC 606 and concluded that Novartis is a customer. The Company identified the following performance obligations that it deemed to be distinct at the inception of the contract:
|
|
|
|
|
|
The Company considered the licenses as functional intellectual property as NovartisAimmune has the right to access its technology and such technology is functional to Novartisuse XmAb7195 at the time that the Company provides access. Under the Novartis Agreement, Novartis has substitutiontransfers such rights. The rights under each discovery program provided it has not advanced to filing an IND. The Company’s obligation to provide services related to the discovery programs, and Novartis’ rightXmAb7195 data are not considered to substitute programs is limited to the five-year periodbe separate from the datelicense to XmAb7195 as Aimmune cannot benefit from the license without the supporting data and documentation.
101
The Company determined the transaction price at inception is $9.6 million which consists of the $150$5.0 million upfront payment and the 156,238 shares of Aimmune common stock which had a value of $4.6 million on the closing date. The Company determined that the transaction price is to be allocated to the performance obligations. The NovartisAimmune Agreement includes variable consideration for potential future milestones and royalties that wereare contingent on future success factors for development programs.the XmAb7195 program. The Company used the “most likely”likely amount” method to determine the variable consideration. None of the development, regulatory or sales milestones or royalties were included in the transaction price. The Company will re-evaluate the transaction price in each reporting period as uncertain events are resolved or other changes in circumstances occur.
The Company determined the transaction price at inception of the NovartisAimmune Agreement and allocated it to the variousperformance obligation, delivery of the XmAb7195 license.
The Company completed delivery of its performance obligations in March 2020. The license to XmAb7195 was transferred to Aimmune at inception of the Aimmune Agreement, and the XmAb7195 data were transferred to Aimmune in March 2020.
The Company recognized $9.6 million of revenue related to the agreement for the year ended December 31, 2020. There is 0 deferred revenue as of December 31, 2020 related to this agreement.
Genentech
In February 2019, the Company entered into a collaboration and license agreement (the Genentech Agreement) with Genentech, Inc. and F. Hoffman-La Roche Ltd (collectively, Genentech) for the development and commercialization of novel IL-15 collaboration products (Collaboration Products), including XmAb306, the Company’s IL-15/IL15Rα-Fc candidate.
Under the terms of the Genentech Agreement, Genentech received an exclusive worldwide license to XmAb306 and other Collaboration Products, including any new IL-15 programs identified during the joint research collaboration. Genentech and Xencor will jointly collaborate on worldwide development of XmAb306 and potentially other Collaboration Products.
The Company received a $120.0 million upfront payment and is eligible to receive up to an aggregate of $160.0 million in clinical milestone payments for XmAb306 and up to $180.0 million in clinical milestone payments for each new Collaboration Product. The Company is also eligible to receive 45% share of net profits for sales of XmAb306 and other Collaboration Products, while also sharing in net losses at the same percentage rate. The parties will jointly share in development and commercialization costs for all programs designated as a development program under the Genentech Agreement at the same percentage rate, while Genentech will bear launch costs entirely. The initial 45% profit-cost share percentage is subject to a one-time downward adjustment at the Company’s discretion and convertible to a royalty under certain circumstances.
Pursuant to the Genentech Agreement, XmAb306 is designated as a development program and all costs incurred for developing both XmAb306 is being shared with Genentech under the initial cost-sharing percentage.
Under the Genentech Agreement, the Company and Genentech will conduct joint research activities for a two-year period to identify and discover additional IL-15 candidates developed from the Company’s cytokine and bispecific technologies. The two-year research term may be extended an additional year if both parties agree. The Company and Genentech are each responsible for their own costs in conducting the research activities. The Company is eligible for clinical milestone payments for new Collaboration Products identified from the research efforts.
The Company evaluated the Genentech Agreement under the provisions of ASU No. 2014-09, Revenue from Contracts with Customers and all related amendments (collectively, ASC 606) as well as ASC 808, Collaborative Arrangements. Certain provisions of the Genentech Agreement including the cost-sharing of development programs are governed by ASC 808. We have determined that Genentech is a customer for purposes of the delivery of specific performance obligations under the Genentech Agreement and applied the provisions of ASC 606 to the transaction.
102
The Company identified the following performance obligations under the Genentech Agreement: (i) the license of XmAb306 and (ii) research services during a two-year period to identify up to potentially 9 additional IL-15 candidates, each a separate research program and a separate performance obligation. The Company determined that the license and each of the potential research programs are separate performance obligations because they are capable of being distinct and are distinct in the context of the Genentech Agreement. The license to XmAb306 has standalone functionality as Genentech has exclusive worldwide rights to the program, including the right to sublicense to third parties. Upon the transfer of the license of XmAb306, Genentech could develop and commercialize XmAb306 without further assistance from the Company. The Company determined that the research services for each potential additional IL-15 candidate and research program were separate standalone performance obligations. The Genentech Agreement provides an outline of an integrated research plan for the programs to be conducted by the 2 companies, and the research activities are separate and distinct from the license to XmAb306. In October 2020, an additional program was declared a Collaboration Program under the Agreement, and the Company completed its performance obligation for that specific research program as the program and licensed rights were transferred to Genentech.
The Company determined the standalone selling price of the license to be $114.4 million using the adjusted market assessment approach considering similar collaboration and license agreements and transactions. The standalone selling price for the research activities for all 9 of the potential IL-15 programs to be performed during the research term was determined to be $8.5 million using the expected cost approach which was derived from the Company’s experience and information from providing similar research activities to other parties.
The Company determined that the transaction price of the Genentech Agreement at inception was $120.0 million consisting of the upfront payment. The potential milestones are not included in the transaction price as these are contingent on future events and the Company would not recognize these in revenue until it is not probable that these would not result in significant reversal of revenue amounts in future periods. The Company will re-assess the transaction price at each reporting period and when event outcomes are resolved or changes in circumstances occur.
The Company allocated the transaction price to each of the separate performance obligations using the relative standalone selling price which is comparablewith $111.7 million allocated to the relativelicense to XmAb306, $4.1 million allocated to the additional program and $4.2 million allocated to the research services.
The Company recognized the $111.7 million allocated to the license when it satisfied its performance obligation and transferred the license to Genentech in March 2019. The license was transferred upon the effective date of the Genentech Agreement, and the $8.3 million allocated to the research activities is being recognized over a period of time through the end of the research term or the time that a program is delivered to Genentech. A total of $3.5 million and $2.2 million of revenue related to the research activities was recognized for the years ended December 31, 2020 and December 31, 2019, respectively.
For the years ended December 31, 2020 and December 31, 2019, we recognized $3.5 million and $113.9 million of income, respectively from the Genentech Agreement. As of December 31, 2020, there is a $3.2 million payable related to cost-sharing development activities during the fourth quarter of 2020. There is $2.5 million in deferred revenue as of December 31, 2020 which reflects our obligation to perform research services during the remaining research term.
Astellas
Effective March 29, 2019, the Company entered into a Research and License Agreement (Astellas Agreement) with Astellas Pharma Inc. (Astellas) pursuant to which the Company and Astellas will conduct a discovery program to characterize compounds and products for development and commercialization. Under the Astellas Agreement, Astellas was granted a worldwide exclusive license, with the right to sublicense products in the field created by the research activities.
103
Pursuant to the Astellas Agreement, the Company applied its bispecific Fc technology to research antibodies provided by Astellas to generate bispecific antibody candidates and returned the candidates to Astellas for further development and commercialization. The activities were conducted under a research plan agreed to by both parties to the Astellas Agreement. Astellas will assume full responsibility for development and commercialization of the antibody candidate. Pursuant to the Astellas Agreement, the Company received an upfront payment of $15.0 million and is eligible to receive up to $240.0 million in milestones, which include $32.5 million in development milestones, $57.5 million in regulatory milestones and $150.0 million in sales milestones. If commercialized, the Company is eligible to receive royalties on net sales that range from the high-single to low-double digit percentages.
We evaluated the Astellas Agreement under ASC 606 and identified the performance obligations under the Agreement to be (i) delivery of bispecific antibodies to Astellas from the antigen provided by Astellas and (ii) research activities against the bispecific antibodies as outlined in the research plan.
The Company determined the standalone selling price methodology used inof the original accounting treatmentbispecific deliverable to be $17.1 million and the standalone selling price for the transaction.research activities to be performed was determined to be $1.4 million.
The Company determined that the transaction price of $150the Astellas Agreement is $17.5 million consisting of the upfront payment and an initial milestone of $2.5 million for Astellas initiating an IND enabling study. The additional milestones are not included in the transaction price as these are contingent on future events, and the Company would not recognize these in revenue until it is not probable that these would not result in significant reversal of revenue amounts in future periods. The Company will re-assess the transaction price at each reporting period and when event outcomes are resolved or changes in circumstances occur.
The Company allocated the transaction price to each of the separate performance obligations using the relative standalone selling price with $16.1 million allocated to delivery of the bispecific antibodies and the remainder of $1.4 million was allocated to the research activities.
The Company recognized the $13.6 million allocated to the bispecific antibodies when it satisfied its performance obligationsobligation to Astellas in 2019 and recognized $2.5 million related to the milestone in 2020. The $1.4 million allocated to the research activities was recognized as follows:the research services were completed.
We recognized $3.5 million and $14.0 million of revenue under this arrangement for the years ended December 31, 2020 and December 31, 2019, respectively. There is a $2.5 million contract asset recorded at December 31, 2020 related to a milestone. There is 0 and $1.0 million in deferred revenue as of December 31, 2020 and December 31, 2019, respectively.
Novartis
In June 2016, the Company entered into a Collaboration and License Agreement (Novartis Agreement) with Novartis Institutes for BioMedical Research, Inc. (Novartis), to develop and commercialize bispecific and other Fc engineered antibody drug candidates using the Company’s proprietary XmAb technologies and drug candidates. Pursuant to the Novartis Agreement:
| The Company granted Novartis certain exclusive rights to research, develop and commercialize XmAb14045 (vibecotamab) and XmAb13676 (plamotamab), 2 development stage products that incorporate the Company’s bispecific Fc technology; |
| The Company will apply its bispecific technology in up to 4 target pair antibodies identified by Novartis (each a Global Discovery Program); and |
| ● | The Company will provide Novartis with a non-exclusive license to certain |
|
|
104
|
|
In December 2018, Novartis notified the Company it was terminating its rights with respect to the plamotamab program, which became effective June 2019. Under the Novartis Agreement, Novartis is responsible to fund its share of plamotamab development costs through June 2020. In November 2019, the Company and Novartis amended the Agreement, and Novartis paid the Company $1.4 million in settlement of its projected remaining cost-sharing due for the plamotamab program. We completed delivery of a Global Discovery Program in 2017 and delivery of a second Global Discovery Program in 2018. In December 2019, Novartis dosed a patient in a Phase 1 study with an undisclosed bispecific antibody that is a Global Discovery Program, and we received a $10.0 million milestone payment. Novartis will assume full responsibility for development and commercialization of each product candidate under each of the Global Discovery Programs. |
|
|
Under ASC 606, revenue is recognized at the time that the Company’s performance obligation for each Global Discovery is completed upon delivery of each discovery program to Novartis. The Company delivered a discovery program to Novartis in 2017 and recognized $20.05$20.1 million of revenue in the period of delivery. In the third quarter of 2018, the Company delivered a second discovery program to Novartis and is recognizingrecognized an additional $20.04$20.0 million of revenue.
Under ASC 606 In the entire amount of revenue allocated to the Fc licenses is being recognized at inception of the Novartis Agreement, the secondthird quarter of 2016.2019, Novartis received notice of approval for an investigational new study (IND) from the Food and Drug Administration (FDA) for an application submitted for a Global Discovery Program, and we recognized $10.0 million of revenue.
During the year ended December 31, 2018, 20172019 and 2016,2018, the Company recognized $20.0 million, $20.1$10.0 million and $69.9$20.0 million of revenue respectively. As ofNaN revenue was recognized during the year ended December 31, 2018 there2020. There is a receivable of $2.1$0.9 million and $12.2 million as of December 31, 2020 and December 31, 2019, respectively, related to the arrangement, and we have recorded $40.1 million in deferred revenue as of December 31, 2020 related to the arrangement.
105
Amgen Inc.
In September 2015, the Company entered into a research and license agreement (the Amgen Agreement) with Amgen Inc. (Amgen) to develop and commercialize bispecific antibody product candidates using the Company’s proprietary XmAb® bispecific Fc technology. Under the Amgen Agreement, the Company granted an exclusive license to Amgen to develop and commercialize bispecific drug candidates from the Company’s preclinical program that bind the CD38 antigen and the cytotoxic T-cell binding domain CD3, (the CD38 Program).Program. The Company also agreed to apply its bispecific technology to five5 previously identified Amgen provided targets (each a Discovery Program). The Company received a $45$45.0 million upfront payment and milestones totaling $15.5 million from Amgen and is eligible to receive up to $600$255.0 million in future development, regulatory and sales milestones in total for programs in development and is eligible to receive royalties on any global net sales of products.
Pursuant to the Amgen Agreement, the Company applied its bispecific technology to five Discovery Programs antibody molecules provided by Amgen that bind Discovery Program targets and returned the bispecific product candidates to Amgen for further testing, development and commercialization. The initial research term was three years from the date of the Amgen Agreement, but Amgen, at its option, may request an extension of one year. In May 2018, Amgen notified the Company that it was electing to extend the term of the research term for one year. Pursuant to the Amgen Agreement, Amgen and the Company will agree upon a detailed plan for services to be provided by the Company during the extended research term. The Company will receive research funding for the additional services provided during the extended research term.
Amgen will assume full responsibility for development and commercialization of product candidates under each of the Discovery Programs.
The Company evaluated the Amgen Agreement under ASC 606 and determined that it is a customer and that delivery of the CD38 Program and each of the five5 Discovery Programs represent the performance obligations under the contract.
The Company determined the transaction price at inception is the $45$45.0 million upfront payment to be allocated to the performance obligations. The Amgen Agreement includes variable consideration for potential future milestones and royalties that were contingent on future success factors for development programs. The Company used the “most likely” method to determine the variable consideration. In the fourth quarter of 2017,2019, the Company receivedrecognized a $10$5.0 million development milestone related to the CD38 program, now AMG424, and this payment was included in the transaction price as uncertainty associated with it has been resolved. In the fourth quarter of 2018, the Company received a $0.5 million preclinical milestone related to one1 of the discovery programs. NoDiscovery Programs. NaN other development, regulatory or sales milestones or royalties were included in the transaction price. 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 allocating the transaction price determined at inception, the Company determined that ASC 606 provides the use of a standalone selling price for the transaction.
The transaction price of $55.5 million was allocated to the performance obligations as follows:
|
|
|
|
Under ASC 606, the amount of revenue recognized for the CD38 program is recognized at the inception of the contract when delivery of the CD38 Program and materials was transferred to Amgen. The $10 million milestone revenue was recognized in the period that the uncertainty regarding the event is resolved, i.e., when the milestone event occurred.
106105
The Company completed performance obligations forunder the five discovery programs in 2016 when all five of the Discovery Programs were delivered to Amgen. Pursuant to ASC 606 the Company recognized $31.25 million of revenue for delivery of the five discovery programs in 2016. In the fourth quarter of 2018, a $0.5 million milestone payment was received in connection with a preclinical development of a discovery program.
Amgen Agreement. In the third quarter of 2018, the Company and Amgen agreed upon additional scope of work to be performed by the Company; the work has been completed2019, a $5.0 million milestone was recognized in 2018.connection with a development milestone for a Discovery Program.
During the years ended December 31, 2018, 20172019 and 2016,2018, the Company recognized $0.6 million, $10.0$5.0 million and $31.2$0.6 million in revenue, respectively, under this arrangement. NaN revenue was recognized for the year ended December 31, 2020. As of December 31, 20182020, there was no0 deferred revenue related to the arrangement.
Novo Nordisk A/S
In December 2014, the Company entered into a Collaboration and License Agreement with Novo Nordisk A/S (Novo). Under the terms of the agreement, the Company granted Novo a research license to use certain Company technologies during a two-year research term. The Company received an upfront payment of $2.5 million and research funding of $1.6 million per year over the research term. This agreement was terminated by Novo in 2016.
There was no revenue recognized for the year ended December 31, 2018 and 2017. For the year ended in December 31, 2016, the total revenue recognized under this agreement was $2.7 million. As of December 31, 2018 the Company has no deferred revenue related to the agreement.
MorphoSys AgAG
In June 2010, the Company entered into a Collaboration and License Agreement with MorphoSys AG (MorphoSys), which was subsequently amended in March 2012.2012 and in 2020. The agreement provided us an upfront payment of $13 million in exchange forprovides MorphoSys with an exclusive worldwide license to the Company’s patents and know‑howknow-how to research, develop, and commercialize ourthe Company’s XmAb5574 product candidate (subsequently renamed MOR208)MOR208 and tafasitamab) with the right to sublicense under certain conditions. Under the agreement, the Company agreed to collaborate with MorphoSys to develop and commercialize XmAb5574/MOR208. If certain developmental, regulatory, and sales milestones are achieved, the Company is eligible to receive future milestone payments and royalties.
In June 2017, MorphoSys initiated a Phase III clinical trial under the arrangement for which the Company received a milestone payment of $12.5 million. The Company recognized the payment asa total of $37.5 million of milestone revenue related to regulatory submission and approval of MorphoSys’ tafasitamab in the period that the milestone event occurred.
The Company recognized $12.5U.S., now Monjuvi, and royalties of $1.5 million on net sales of revenueMonjuvi for the year endended December 31, 2017.2020. There were no0 revenues recognized under this arrangement for the years ended December 31, 20182019 and 2016.2018. As of December 31, 2018,2020, the Company has no0 deferred revenue related to this agreement.agreement and has recorded a receivable of $1.2 million for royalties due.
Alexion Pharmaceuticals, Inc.
In January 2013, the Company entered into an option and license agreement with Alexion Pharmaceuticals, Inc. (Alexion). Under the terms of the agreement, the Company granted to Alexion an exclusive research license, with limited sublicensing rights, to make and use our Xtend technology. Alexion exercised its rights to include our technology to evaluate and advance compounds against six different target programs during a five‑year research term under the agreement, up to completion of the first multi‑dose human clinical trial for each target compound.in ALXN1210, which is now marketed as Ultomiris.
107
Under the agreement, the Company received an upfront payment of $3.0 million and also an annual maintenance fee of $0.5 million during the research term of the agreement. In addition, theThe Company is eligible to receive contractual milestones for certain development, regulatory and commercial achievements. If licensed products are successfully commercialized,achievements, and the Company is also entitled to receive royalties based on a percentage of net sales of such products sold by Alexion, its affiliates or its sub licensees, which percentage is in the low single digits. Alexion’s royalty obligations continue on a product‑by‑productproduct-by-product and country‑by‑ countrycountry-by-country basis until the expiration of the last‑to‑expirelast-to-expire valid claim in a licensed patent covering the applicable product in such country.
In December 2016, Alexion achieved a Phase 3 clinical development milestone for ALXN1210.
In the third quarter of 2018, Alexion completed certain regulatory submission filingssubmissions and regulatory approvals for ALXN1210 and the Company received $9 million in milestone payments. In the fourth quarter of 2018, Alexion completed certain regulatory submission filings for ALXN 1210 and also received FDA marketing approval for ALXN 1210, now Ultomiris, and the Company received $11$20.0 million in milestone payments.
The Company determinedIn 2019, Alexion to be a customercompleted certain regulatory submissions for Ultomiris, and the licenseCompany received a total of $8.0 million in milestone payments. During 2019, the Company’s Xtend intellectual property is functional intellectual property, distinctCompany also recorded royalty revenue of $5.0 million in connection with reported net sales of Ultomiris by Alexion.
In 2020, the Company received $10.0 million for the achievement of certain sales milestones of Ultomiris in 2020 and is the only performance obligation under the agreement. The upfront fee, thealso recorded royalty revenue of $16.2 million on net present value of the annual maintenance fees, the option exercise fee and milestone payments of $36.5 million already received represent the total transaction price at inception. The option exercise fee does not provide a discount on future services and does not grant a material right. Under ASC 606 the upfront payment and the present value of the annual licensing fees are recognized at inception of the agreement when Alexion was provided access to the technology.sales.
The total revenue recognized under this arrangement was $20.0$26.2 million, $13.0 million, and $5.0$20.0 million for the years ended December 31, 2020, 2019, and 2018, respectively. As of December 31, 2020, there is a receivable of $8.8 million, and 2016, respectively. Therethere is 0 deferred revenue related to this agreement.
Gilead Sciences, Inc.
In January 2020, the Company entered into a Technology License Agreement (the Gilead Agreement) with Gilead Sciences, Inc. (Gilead), in which the Company provided Gilead an exclusive license to its Cytotoxic Fc and Xtend Fc technologies for an initial identified antibody and options for up to 3 additional antibodies directed to the
106
same molecular target. Gilead is responsible for all development and commercialization activities for all target candidates. The Company received an upfront payment of $6.0 million and is eligible to receive up to $67.0 million in milestones, which include $10.0 million in development milestones, $27.0 million in regulatory milestones and $30.0 million in sales milestones for each product incorporating the antibodies selected. In addition, the Company is eligible to receive royalties in the low-single digit percentage range on net sales of approved products.
In the second quarter of 2020, Gilead exercised options on 3 additional antibody compounds, and in April 2020, we received a total of $7.5 million in payment of the 3 options.
The Company evaluated the Gilead Agreement under the revenue recognition standard ASC 606 and identified the following performance obligations that it deemed to be distinct at the inception of the contract:
| ● | non-exclusive license to its Cytotoxic Fc and Xtend Fc technologies; and |
| ● | options for 4 exclusive commercial licenses to incorporate the licensed technologies on approved target compounds. |
The Company considered the licenses as functional intellectual property as Gilead has the right to use the technologies at the time that the Company transfers such rights. Each of the 4 options is considered a separate performance obligation as the arrangement does not confer material rights to the options without payment of the option exercise fee. Gilead will benefit from each option upon exercise of each of the 4 options and payment of each option fee as Gilead has access to each technology at inception of the arrangement and the rights are transferred upon payment of each option fee.
The total transaction price is $13.5 million which includes the upfront payment of $6.0 million and the option fee payment of $7.5 million which was nocontractually due with the exercise of the 3 options by Gilead. The milestone payments are variable consideration to which the Company applied the “most likely amount” method and concluded at inception of the Gilead Agreement it is unlikely that the Company will collect such payments. The milestone payments were not included in the transaction price, and the Company will review this conclusion and update at each reporting period.
The Company allocated $3.5 million of the transaction price to the licenses to the cytotoxic Fc and Xtend Fc technologies and recognized income for the licenses at inception of the arrangement when Gilead began benefiting access to them. The Company allocated $2.5 million to the initial option exercise which was effective at inception of the arrangement and payment of the upfront amount, and the Company allocated $7.5 million to the 3 remaining options which became effective in April 2020 when Gilead paid the option fees.
The Company recognized $13.5 million of revenue recognizedrelated to the Gilead Agreement for the year ended December 31, 2017. As2020. There is 0 deferred revenue as of December 31, 2018 there is no deferred revenue2020 related to this agreement.
Boehringer Ingelheim International GmbHOmeros Corporation
In 2007August 2020, the Company entered into a Research Licensee and CollaborationTechnology License Agreement (the Omeros Agreement) with Boehringer Ingelheim International GmbH (BI). Under the agreement,Omeros Corporation (Omeros), in which the Company provided BI withOmeros a three‑year researchnon-exclusive license to oneits Xtend Fc technology, an exclusive license to apply its Xtend technology to an initial identified antibody and options to apply its Xtend technology to 3 additional antibodies. Omeros is responsible for all development and commercialization activities for all target candidates. The Company received an upfront payment of $5.0 million and is eligible to receive up to $65.0 million in milestones, which include $15.0 million in development milestones, $25.0 million in regulatory milestones and $25.0 million in sales milestones for each product incorporating the antibodies selected. In addition, the Company is eligible to receive royalties in the mid-single digit percentage range on net sales of approved products.
107
The Company evaluated the Omeros Agreement under the revenue recognition standard ASC 606 and identified the following performance obligations that it deemed to be distinct at the inception of the Company’scontract:
| ● | non-exclusive license to its Xtend Fc technologies; and |
| ● | options for 4 exclusive commercial licenses to incorporate the licensed technologies on approved target compounds. |
The Company considered the license as functional intellectual property as Omeros has the right to use the technology at the time that the Company transfers such rights. Each of the 4 options is considered a separate performance obligation as the arrangement does not confer material rights to the options without payment of the option exercise fee. Omeros will benefit from each option upon exercise of each of the 4 options and commercial options. BI electedpayment of each option fee as Omeros has access to each technology at inception of the arrangement and the rights are transferred upon payment of each option fee.
The total transaction price is $5.0 million, which includes the upfront payment. The milestone payments are variable consideration to which the Company applied the “most likely amount” method and concluded at inception of the Omeros Agreement it is unlikely that the Company will collect such payments. The milestone payments were not included in the transaction price and the Company will review this conclusion and update at each reporting period.
The Company allocated $2.0 million of the transaction price to the licenses to the Xtend Fc technology and recognized income for the licenses at inception of the arrangement when Omeros began benefiting access to it. The Company allocated $3.0 million to the initial option exercise two commercial licenses from compounds identified duringwhich was effective at inception of the research term and one compound is currently in clinical development. Noarrangement.
The Company recognized $5.0 million of revenue related to this arrangement was recognized in 2018, 2017 or 2016. There is no deferred revenue related to this agreement at December 31, 2018.
CSL Limited
In February 2009, the Company entered into a research license and commercialization agreement with CSL Limited (CSL). Under the agreement, the Company provided CSL with a research license to our Fc Cytotoxic technology and options to non-exclusive commercial licenses. CSL elected to exercise one commercial license for a compound, CSL362.
In 2013 CSL sublicensed CSL362 (now called talacotuzumab) to Janssen Biotech Inc. (Janssen Biotech). In March 2017, CSL, through its sub-licensee, Janssen Biotech, initiated a Phase 3 clinical trial for CSL362 and the Company received a milestone payment of $3.5 million.
There was no revenue recognized for the years ended December 31, 2018 and 2016. Total revenue recognizedOmeros Agreement for the year ended December 31, 2017 was $3.5 million. As2020. There is 0 deferred revenue as of December 31, 2018, there2020 related to this agreement.
MiRagen Therapeutics, Inc./Viridian Therapeutics, Inc.
In December 2020, we entered into a Technology License Agreement (MiRagen Agreement) with MiRagen Therapeutics, Inc. (MiRagen), in which we provided MiRagen a non-exclusive license to our Xtend Fc technology and an exclusive license to apply our Xtend Fc technology to antibodies targeting IGF-1R. MiRagen subsequently changed its name to Viridian Therapeutics, Inc. Viridian is noresponsible for all development and commercialization activities. We received an upfront payment of 322,407 shares of Viridian common stock valued at $6.0 million and are eligible to receive up to $55.0 million in milestones, which include $10.0 million in development milestones, $20.0 million in regulatory milestones and $25.0 million in sales milestones. We are also eligible to receive royalties in the mid-single digit percentage range on net sales of approved products.
The Company evaluated the MiRagen Agreement under the revenue recognition standard ASC 606 and identified the following performance obligation that it deemed to be distinct at the inception of the contract:
| ● | non-exclusive license to its Xtend Fc technologies |
The Company considered the license as functional intellectual property as MiRagen has the right to use the technology at the time that the Company transfers such rights.
The total transaction price is $6.0 million, which includes the upfront payment of 322,407 MiRagen shares at their fair value at the date of the Agreement. The milestone payments are variable consideration to which the Company applied the “most likely amount” method and concluded at inception of the MiRagen Agreement it is unlikely that the Company will collect such payments. The milestone payments were not included in the transaction price, and the Company will review this conclusion and update at each reporting period.
108
The Company allocated $6.0 million of the transaction price to the licenses to the Xtend Fc technology and recognized income for the licenses at inception of the arrangement when MiRagen began benefiting access to it. The Company recognized $6.0 million of revenue related to the MiRagen Agreement for the year ended December 31, 2020. There is 0 deferred revenue as of December 31, 2020 related to this agreement.
108
Private Biotech Company License Agreement
Merck Sharp & Dohme Corp.
In July 2013,November 2020, the Company entered into a License Agreement with Merck Sharp & Dohme Corp (Merck).a newly formed, privately held biotechnology company (Private BioCo) pursuant to which the Company granted Private BioCo exclusive worldwide rights to develop and commercialize to 3 preclinical-stage Fc-engineered drug candidates: XmAb6755, XPro9523 and XmAb10717. Under the termsAgreement, Private BioCo will be responsible for all further development and commercialization activities for XmAb6755, XPro9523 and XmAb10717. The Company received a 15% equity interest in Private BioCo with a fair value of $16.1 million, and the Company is eligible to receive royalties on net sales of approved products in the mid-single digit to mid-teen percentage range.
Under the License Agreement, Private BioCo received exclusive worldwide rights to manufacture, develop and commercialize XmAb6755, XPro9523 and XmAb10717. They also received the rights to all data, information and research materials related to the three preclinical stage programs.
The Company evaluated the License Agreement under the revenue recognition standard ASC 606 and identified the following performance obligations that it deemed to be distinct at the inception of the agreement,contract:
| ● | exclusive license to the XmAb6755, XPro9523 and XmAb10717 drug candidates; and |
| ● | rights to material, data, and information that the Company had accumulated in connection with conducting preclinical activities for each of the three programs and intellectual property filings and information. |
The Company considered the licenses as functional intellectual property as Private BioCo has the right to use each of XmAb6755, XPro9523 and XmAb10717 at the time that the Company provided Merck with a non‑exclusive commercialtransfers such rights. The rights to the preclinical programs’ data are not considered to be separate from the license to certain patent rights to our Fc domains to apply to one of their compounds. programs as Private BioCo cannot benefit from the license without the supporting data and documentation.
The agreement provided for antotal transaction price is $16.1 million, which includes the upfront payment of $1.0 million and annual maintenance fees totaling $0.5 million.
In February 2018, Merck provided notice15% of the equity of Private BioCo at its fair value at the date of the Agreement. The License Agreement includes variable consideration for potential future royalties that it is terminatingwere contingent on future success factors for the agreement.licensed programs. The Company did not recognize any revenue for eachused the “most likely amount” method to determine the variable consideration. NaN of the yearsroyalties were included in the transaction price. The Company will re-evaluate the transaction price in each reporting period as uncertain events are resolved or other changes in circumstances occur.
The Company determined the transaction price at inception of the License Agreement and allocated it to the performance obligation, delivery of the XmAb6755, XPro9523 and XmAb10717 licenses.
The Company completed delivery of its performance obligations in December 2020. The licenses to XmAb6755, XPro9523, and XmAb10717 were transferred to Private BioCo at inception of the Agreement, and the related research data and documentation was transferred to Private BioCo in December 2020.
The Company recognized $16.1 million of revenue related to the agreement for the year ended December 31, 2018, 2017 and 2016. As2020. There is 0 deferred revenue as of December 31, 2018, there is no deferred revenue2020 related to this agreement.
109
INmune Bio, Inc.
In October 2017, the Company entered into a License Agreement with INmune Bio, Inc. (INmune). Under the terms of the agreement, the Company provided INmune with an exclusive license to certain rights to a proprietary protein, XPRO1595.XPro1595. Under the agreement the Company received an upfront payment of $100,000, a 19% fully-diluted equity interest in1,585,000 shares of INmune common stock and an option to acquirepurchase an additional 10% interest of the fully diluted shares of INmune.INmune for $10.0 million. The Company is eligible to receive a percentage of sublicensing revenue received for XPRO1595XPro1595 and also royalties in the mid-single digit percent range on the sale of approved products.
The equity interest in INmune constituted 1,585,000 shares of common stock and the option is to purchase an additional 10% of the fully diluted interest in INmune for $10 million.
In 2018, INmune filed a registration statement on a Form S-1 with the Securities and Exchange Commission (SEC) which was declared effective by the SEC as ofon December 19, 2018.
Under ASC 606, the Company determined that the performance obligation under the agreement was the license to XPRO1595XPro1595, and performance occurred at the effective date of the agreement. The total consideration under the agreement was determined to be $100,000 as the equity interest, and the option at inception of the Agreement had an insignificant fair value. The Company recognized $100,000 as revenue related to the agreement for the year ended December 31, 2017 and did not recognize any revenue related to the agreement for the yearyears ended December 31, 2020, 2019, or 2018. There is no0 deferred revenue as of December 31, 20182020 related to this agreement. The INmune shares are recorded at cost on the Company’s balance sheet as of December 31, 2020.
Revenue earnedVir Biotechnology, Inc.
In 2019, the Company entered into a Patent License Agreement (the Vir Agreement) with Vir Biotechnology (Vir) pursuant to which the Company provided a non-exclusive license to its Xtend technology for up to 2 targets. Under the terms of the Vir Agreement, the Company received an upfront payment and is eligible to receive total milestones of $155.0 million which include $5.0 million of development milestones, $30.0 million of regulatory milestones and $120.0 million of sales milestones. In addition, the Company is eligible to receive royalties on the net sales of approved products in the low-single digits.
The $40.6 million, $46.2Company evaluated the Vir Agreement and determined that the single performance obligation was access to a non-exclusive license to certain patents of the Company which were transferred to Vir upon execution of the Vir Agreement in July 2019.
Vir initiated a Phase 1 study with a licensed antibody in 2019, and in the second quarter of 2020, it initiated a Phase 1 study with a second licensed antibody.
In March 2020, the Company entered into a second Patent License Agreement (the Second Vir Agreement) with Vir pursuant to which the Company provided a non-exclusive license to its Xtend technology to extend the half-life of novel antibodies Vir is investigating as potential treatments for patients with COVID-19. Under the terms of the Second Vir Agreement, Vir is responsible for all research, development, regulatory and commercial activities for the antibody, and the Company is eligible to receive royalties on the net sales of approved products in the mid-single digit percentage range.
Vir initiated a Phase 3 study with a licensed antibody to treat patients with COVID-19 in 2020.
The Company determined that the Second Vir Agreement was a modification of the original agreement, and the transfer of the license occurred at inception of the Vir Agreement. The total consideration under the arrangement did not change with the Second Vir Agreement as the Company will potentially receive additional royalty revenue which is variable consideration and is not included in the transaction price.
The Company recognized $0.3 million and $109.0$0.8 million of license and milestone revenue related to the agreement for the years ended December 31, 2020 and 2019, respectively. There is 0 deferred revenue as of December 31, 2020 related to this agreement.
110
Revenue Earned
The $122.7 million, $156.7 million, and $40.6 million of revenue recorded for the years ended December 31, 2020, 2019 and 2018, 2017 and 2016, respectively, waswere earned principally from the following licensees (in millions):
|
|
|
|
|
|
|
|
|
|
|
|
| Year Ended |
| |||||||
|
| December 31, |
| |||||||
|
| 2018 |
| 2017 |
| 2016 |
| |||
|
|
|
| (As Revised) |
| (As Revised) |
| |||
Amgen |
| $ | 0.6 |
| $ | 10.0 |
| $ | 31.2 |
|
Alexion |
|
| 20.0 |
|
| — |
|
| 5.0 |
|
CSL |
|
| — |
|
| 3.5 |
|
| — |
|
MorphoSys |
|
| — |
|
| 12.5 |
|
| — |
|
Novo Nordisk |
|
| — |
|
| — |
|
| 2.7 |
|
Novartis |
|
| 20.0 |
|
| 20.1 |
|
| 69.9 |
|
Other |
|
| — |
|
| 0.1 |
|
| 0.2 |
|
Total |
| $ | 40.6 |
| $ | 46.2 |
| $ | 109.0 |
|
| | | | | | | | | | |
| | Year Ended |
| |||||||
| | December 31, |
| |||||||
| | 2020 | | 2019 | | 2018 |
| |||
Aimmune |
| $ | 9.6 |
| $ | — |
| $ | — | |
Amgen | | | — | |
| 5.0 | |
| 0.6 | |
Alexion | | | 26.2 | |
| 13.0 | |
| 20.0 | |
Astellas | | | 3.5 | |
| 14.0 | |
| — | |
Genentech | | | 3.5 | |
| 113.9 | |
| — | |
Gilead | | | 13.5 | |
| — | |
| — | |
MiRagen/Viridian | | | 6.0 | |
| — | |
| — | |
MorphoSys | | | 39.0 | |
| — | |
| — | |
Novartis | | | — | |
| 10.0 | |
| 20.0 | |
Omeros | | | 5.0 | |
| — | |
| — | |
Vir | | | 0.3 | |
| 0.8 | |
| — | |
Private BioCo | | | 16.1 | |
| — | |
| — | |
Total | | $ | 122.7 | | $ | 156.7 | | $ | 40.6 | |
109
The table below table summarizes the disaggregation of revenue recorded for the years ended December 31, 2018, 20172020, 2019 and 20162018 (in millions):
|
|
|
|
|
|
|
|
|
| |||||||||
|
| Year Ended | ||||||||||||||||
|
| December 31, | ||||||||||||||||
|
| 2018 |
| 2017 |
| 2016 | ||||||||||||
|
|
|
| (As Revised) |
| (As Revised) | ||||||||||||
| | | | | | | | | | |||||||||
| | Year Ended | ||||||||||||||||
| | December 31, | ||||||||||||||||
| | 2020 | | 2019 | | 2018 | ||||||||||||
Research collaboration |
| $ | 20.1 |
| $ | 20.1 |
| $ | 34.2 |
| $ | 4.5 |
| $ | 16.3 |
| $ | 20.1 |
Milestone |
|
| 20.5 |
|
| 26.0 |
|
| 5.0 | | | 50.2 | |
| 23.2 | |
| 20.5 |
Licensing |
|
| — |
|
| 0.1 |
|
| 69.8 | | | 50.2 | |
| 112.2 | |
| — |
Royalties | | | 17.8 | |
| 5.0 | |
| — | |||||||||
Total |
| $ | 40.6 |
| $ | 46.2 |
| $ | 109.0 | | $ | 122.7 | | $ | 156.7 | | $ | 40.6 |
A portion of our revenue is earned from collaboration partners outside the United States. Non‑U.S.Non-U.S. revenue is denominated in U.S. dollars. A breakdown of our revenue from U.S. and Non‑U.S.non-U.S. sources for the years ended December 31, 2018, 20172020, 2019 and 20162018 is as follows (in millions):
|
|
|
|
|
|
|
|
|
| |||||||||||
|
| Year Ended |
| |||||||||||||||||
|
| December 31, |
| |||||||||||||||||
|
| 2018 |
| 2017 |
| 2016 |
| |||||||||||||
|
|
|
|
| (As Revised) |
| (As Revised) |
| ||||||||||||
| | | | | | | | | | | ||||||||||
| | Year Ended |
| |||||||||||||||||
| | December 31, |
| |||||||||||||||||
| | 2020 | | 2019 | | 2018 |
| |||||||||||||
U.S. Revenue |
| $ | 40.6 |
| $ | 30.2 |
| $ | 106.3 |
|
| $ | 64.1 |
| $ | 142.7 |
| $ | 40.6 | |
Non-U.S. Revenue |
|
| — |
|
| 16.0 |
|
| 2.7 |
| | | 58.6 | | | 14.0 | | | — | |
Total |
| $ | 40.6 |
| $ | 46.2 |
| $ | 109.0 |
| | $ | 122.7 | | $ | 156.7 | | $ | 40.6 | |
Remaining Performance Obligations and Deferred Revenue
Our only remaining performance obligations are thedelivery of 2 additional Global Discovery Programs under the Novartis Agreement.Agreement and conducting research activities pursuant to research plans under the Genentech and Janssen Agreements. As of December 31, 20182020 and 2017,2019, we have deferred revenue of $40.1$92.6 million and $60.1$47.1 million, respectively. We classifiedAll of the deferred revenue was classified as short term as of December 31, 2020 as our obligations to perform research services are due on demand when requested by Novartis, Genentech and Janssen under the respective Agreements. As of December 31, 2019, $45.2 million of deferred revenue was classified as current liabilities as our
111
obligations to perform services are due on demand when requested by Novartis and Astellas under the Agreement.Novartis and Astellas Agreements, respectively. A total of $1.9 million of deferred liability is classified as long-term for the obligation to perform research services to Genentech under the Genentech Agreement after one year.
10.11. 401(k) Plan
We have a 401(k) plan-plan covering all full‑timefull-time employees. Employees may make pre‑taxpre-tax contributions up to the maximum allowable by the Internal Revenue Code. Effective January 1, 2018, the Company contributes 100% of the first 1% of participating employees’ contribution and 50% of the next 5% of participating employees’ contribution, for a maximum of 3.5% employer contribution. Effective March 31, 2020, the Company contributes 100% of the first 1% of participating employees’ contribution and 50% of the next 6% of participating employees’ contribution, for a maximum of 4.0% of employer contribution. Participants are immediately vested in their employee contributions; employer contributions are vested over a three-year period with one-thirdone-third for each year of a participating employee’s service. Employer contributions made for the year ended December 31, 2018 was $0.5 million. No employer contributions were made for the years ended December 31, 20172020, 2019, and 2016.2018 were $0.8 million, $0.6 million and $0.5 million, respectively.
11.12. Condensed Quarterly Financial Data (unaudited)
The following table contains selected unaudited financial data for each quarter of 20182020 and 2017.2019. The unaudited information should be read in conjunction with the Company’s financial statements and related notes included elsewhere in this report.Annual Report. The Company believes that the following information reflects all normal recurring adjustments necessary for a fair presentation of the information for the periods presented. The operating results for any quarter are not necessarily indicative of results for any future period.
110
Quarterly Financial Data (in thousands, except per share data):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 2018 Quarter Ended |
| ||||||||||
|
| March 31, |
| June 30, |
| September 30, |
| December 31, |
| ||||
Total revenue |
| $ | — |
| $ | — |
| $ | 29,039 |
| $ | 11,564 |
|
Income (loss) from operations |
|
| (30,649) |
|
| (28,290) |
|
| 651 |
|
| (21,082) |
|
Net income (loss) |
|
| (29,493) |
|
| (25,869) |
|
| 3,150 |
|
| (18,197) |
|
Basic net income (loss) per common share |
|
| (0.62) |
|
| (0.46) |
|
| 0.06 |
|
| (0.32) |
|
Diluted net income (loss) per common share |
|
| (0.62) |
|
| (0.46) |
|
| 0.05 |
|
| (0.32) |
|
| | | | | | | | | | | | | |
| | 2020 Quarter Ended |
| ||||||||||
|
| March 31, |
| June 30, |
| September 30, |
| December 31, |
| ||||
Total revenue | | $ | 32,385 | | $ | 13,089 | | $ | 35,366 | | $ | 41,854 | |
Loss from operations | |
| (8,777) | |
| (37,600) | |
| (16,722) | |
| (13,698) | |
Net loss | |
| (8,074) | |
| (35,018) | |
| (12,550) | |
| (13,691) | |
Basic net loss per common share | |
| (0.14) | |
| (0.61) | |
| (0.22) | |
| (0.24) | |
Diluted net loss per common share | | | (0.14) | | | (0.61) | | | (0.22) | | | (0.24) | |
|
|
|
|
|
|
|
|
|
|
|
|
|
| |||||||||||||
|
| 2017 Quarter Ended |
| |||||||||||||||||||||||
|
| March 31, |
| June 30, |
| September 30, |
| December 31, |
| |||||||||||||||||
|
| (As Revised) |
| (As Revised) |
| (As Revised) |
| (As Revised) |
| |||||||||||||||||
| | | | | | | | | | | | | | |||||||||||||
| | 2019 Quarter Ended |
| |||||||||||||||||||||||
| | March 31, | | June 30, | | September 30, | | December 31, |
| |||||||||||||||||
Total revenue |
| $ | 3,500 |
| $ | 12,500 |
| $ | — |
| $ | 30,150 |
|
| $ | 111,939 | | $ | 19,485 | | $ | 21,760 | | $ | 3,516 | |
Income (loss) from operations |
|
| (16,359) |
|
| (8,510) |
|
| (23,580) |
|
| 5,326 |
| |
| 78,244 | |
| (19,572) | |
| (14,276) | |
| (30,572) | |
Net income (loss) |
|
| (15,475) |
|
| (7,725) |
|
| (22,652) |
|
| 7,366 |
| |
| 80,045 | |
| (16,034) | |
| (10,224) | |
| (26,912) | |
Basic net income (loss) per common share |
|
| (0.33) |
|
| (0.17) |
|
| (0.48) |
|
| 0.16 |
| |
| 1.42 | |
| (0.28) | |
| (0.18) | |
| (0.47) | |
Diluted net income (loss) per common share |
|
| (0.33) |
|
| (0.17) |
|
| (0.48) |
|
| 0.15 |
| | | 1.38 | | | (0.28) | | | (0.18) | | | (0.47) | |
12. Prior-Period Financial Statements
The Company adopted ASC 606 on January 1, 2018 using the full retrospective method and as a result the Company has revised its comparative financial statements for the prior period as if ASC 606 had been in effect for that period.
The most significant changes to revenue recognition under ASC 606 relate to the timing of revenue recognized for arrangements that include licensing of our technologies. Under ASC 606 revenue related to licensing of access to our technologies is recognized at inception of the agreement, generally the effective date of the agreement. For existing licensing arrangements, the effect of ASC 606 is to shift revenue to earlier periods. Approximately $11.3 million of licensing revenue that was being recognized over the five-year period 2016-2021 is being recognized in the second quarter of 2016.
The other significant change under ASC 606 relates to the timing of collaboration revenue when the Company completes its performance obligations for delivery of a drug candidate to its collaboration partners after applying its technologies. For existing collaborations, the effect of ASC 606 is to accelerate revenue recognition to earlier periods. Approximately $6.25 million of collaboration revenue recognized in 2017 and 2018 under historical accounting guidance is being recognized in 2016 under ASC 606. An additional $20.5 million of collaboration revenue that would be recognized in 2018 is being recognized in 2017. The following tables summarize the effects of adopting ASC topic 606 on our financial statements.
111
Balance Sheet
|
|
|
|
|
|
|
|
|
| As Reported |
| Effect of Adoption of |
| As Revised | |||
| 2017 |
| ASC 606 |
| 2017 | |||
|
|
|
|
|
| |||
Assets |
|
|
|
|
|
|
|
|
Current assets |
|
|
|
|
|
|
|
|
Cash and cash equivalents | $ | 16,528 |
| $ | — |
| $ | 16,528 |
Marketable securities |
| 207,603 |
|
| — |
|
| 207,603 |
Accounts receivable |
| 1,142 |
|
| — |
|
| 1,142 |
Prepaid expenses and other current assets |
| 5,606 |
|
| — |
|
| 5,606 |
Total current assets |
| 230,879 |
|
| — |
|
| 230,879 |
Property and equipment, net |
| 7,088 |
|
| — |
|
| 7,088 |
Patents, licenses, and other intangible assets, net |
| 11,148 |
|
| — |
|
| 11,148 |
Marketable securities - long term |
| 139,198 |
|
| — |
|
| 139,198 |
Income tax receivable |
| 1,524 |
|
| — |
|
| 1,524 |
Loan receivable |
| — |
|
| 86 |
|
| 86 |
Interest receivable |
| — |
|
| 14 |
|
| 14 |
Other assets |
| 265 |
|
| — |
|
| 265 |
Total assets | $ | 390,102 |
| $ | 100 |
| $ | 390,202 |
Liabilities and stockholders’ equity |
|
|
|
|
|
|
|
|
Current liabilities |
|
|
|
|
|
|
|
|
Accounts payable | $ | 6,869 |
| $ | — |
| $ | 6,869 |
Accrued expenses |
| 5,480 |
|
| — |
|
| 5,480 |
Current portion of deferred rent |
| 26 |
|
| — |
|
| 26 |
Current portion of deferred revenue |
| 88,813 |
|
| (28,695) |
|
| 60,118 |
Income taxes |
| 157 |
|
| — |
|
| 157 |
Total current liabilities |
| 101,345 |
|
| (28,695) |
|
| 72,650 |
Deferred rent, less current portion |
| 1,088 |
|
| — |
|
| 1,088 |
Deferred revenue, less current portion |
| 5,623 |
|
| (5,623) |
|
| — |
Total liabilities |
| 108,056 |
|
| (34,318) |
|
| 73,738 |
Commitments and contingencies |
|
|
|
|
|
|
|
|
Stockholders’ equity |
|
|
|
|
|
|
|
|
Preferred stock, $0.01 par value: 10,000,000 authorized shares; -0- issued and outstanding shares at December 31, 2017 |
| — |
|
| — |
|
| — |
Common stock, $0.01 par value: 200,000,000 authorized shares at December 31, 2017; 47,002,488 issued and outstanding at December 31, 2017 |
| 470 |
|
| — |
|
| 470 |
Additional paid-in capital |
| 570,670 |
|
| — |
|
| 570,670 |
Accumulated other comprehensive income loss |
| (1,808) |
|
| — |
|
| (1,808) |
Accumulated deficit |
| (287,286) |
|
| 34,418 |
|
| (252,868) |
Stockholders’ equity |
| 282,046 |
|
| 34,418 |
|
| 316,464 |
Total liabilities and stockholders’ equity | $ | 390,102 |
| $ | 100 |
| $ | 390,202 |
112
Statement of Operation
|
|
|
|
|
|
|
|
|
|
|
| As Reported |
|
|
|
| As Revised | ||
|
| Year Ended |
| Effect of |
| Year Ended | |||
|
| December 31, |
| Adoption of |
| December 31, | |||
|
| 2017 |
| ASC 606 |
| 2017 | |||
|
|
|
|
|
|
|
|
|
|
Revenue |
|
|
|
|
|
|
|
|
|
Collaborations, licenses and milestones |
| $ | 35,711 |
| $ | 10,439 |
| $ | 46,150 |
Operating expenses |
|
|
|
|
|
|
|
|
|
Research and development |
|
| 71,772 |
|
| — |
|
| 71,772 |
General and administrative |
|
| 17,501 |
|
| — |
|
| 17,501 |
Total operating expenses |
|
| 89,273 |
|
| — |
|
| 89,273 |
Loss from operations |
|
| (53,562) |
|
| 10,439 |
|
| (43,123) |
Other income (expenses) |
|
|
|
|
|
|
|
|
|
Interest income |
|
| 4,194 |
|
| — |
|
| 4,194 |
Interest expense |
|
| (13) |
|
| — |
|
| (13) |
Other income |
|
| (7) |
|
| — |
|
| (7) |
Total other income, net |
|
| 4,174 |
|
| — |
|
| 4,174 |
|
|
|
|
|
|
|
|
|
|
Loss before income tax benefit |
|
| (49,388) |
|
| 10,439 |
|
| (38,949) |
Income tax benefit |
|
| (463) |
|
| — |
|
| (463) |
Net loss |
|
| (48,925) |
|
| 10,439 |
|
| (38,486) |
|
|
|
|
|
|
|
|
|
|
Other comprehensive loss |
|
|
|
|
|
|
|
|
|
Net unrealized loss on marketable securities |
|
| (367) |
|
| — |
|
| (367) |
Comprehensive loss |
| $ | (49,292) |
| $ | 10,439 |
| $ | (38,853) |
|
|
|
|
|
|
|
|
|
|
Basic and diluted net loss per common share |
| $ | (1.05) |
| $ | 0.23 |
| $ | (0.82) |
|
|
|
|
|
|
|
|
|
|
113
|
|
|
|
|
|
|
|
|
|
|
| As Reported |
|
|
|
| As Revised | ||
|
| Year Ended |
| Effect of |
| Year Ended | |||
|
| December 31, |
| Adoption of |
| December 31, | |||
|
| 2016 |
| ASC 606 |
| 2016 | |||
|
|
|
|
|
|
|
|
|
|
Revenue |
|
|
|
|
|
|
|
|
|
Collaborations, licenses and milestones |
| $ | 87,520 |
| $ | 21,500 |
| $ | 109,020 |
Operating expenses |
|
|
|
|
|
|
|
|
|
Research and development |
|
| 51,872 |
|
| — |
|
| 51,872 |
General and administrative |
|
| 13,108 |
|
| — |
|
| 13,108 |
Total operating expenses |
|
| 64,980 |
|
| — |
|
| 64,980 |
Income from operations |
|
| 22,540 |
|
| 21,500 |
|
| 44,040 |
Other income (expenses) |
|
|
|
|
|
|
|
|
|
Interest income |
|
| 2,091 |
|
| — |
|
| 2,091 |
Interest expense |
|
| (21) |
|
| — |
|
| (21) |
Other income |
|
| 6 |
|
| — |
|
| 6 |
Total other income, net |
|
| 2,076 |
|
| — |
|
| 2,076 |
|
|
|
|
|
|
|
|
|
|
Income before income tax expense |
|
| 24,616 |
|
| 21,500 |
|
| 46,116 |
Income tax expense |
|
| 991 |
|
| — |
|
| 991 |
Net income |
|
| 23,625 |
|
| 21,500 |
|
| 45,125 |
|
|
|
|
|
|
|
|
|
|
Other comprehensive loss |
|
|
|
|
|
|
|
|
|
Net unrealized loss on marketable securities |
|
| (925) |
|
| — |
|
| (925) |
Comprehensive income |
| $ | 22,700 |
| $ | 21,500 |
| $ | 44,200 |
|
|
|
|
|
|
|
|
|
|
Basic net income per common share |
| $ | 0.57 |
| $ | 0.52 |
| $ | 1.09 |
Diluted net income per common share |
| $ | 0.56 |
| $ | 0.51 |
| $ | 1.07 |
|
|
|
|
|
|
|
|
|
|
114
Statement of Stockholders’ Equity
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Accumulated |
|
|
|
|
|
| |
|
|
|
|
|
|
| Additional |
| Other |
|
|
|
| Total | |||
|
| Common Stock |
| Paid |
| Comprehensive |
| Accumulated |
| Stockholders’ | |||||||
Stockholders’ Equity |
| Shares |
| Amount |
| in-Capital |
| Loss |
| Deficit |
| Equity | |||||
Balance, December 31, 2016 as originally reported |
| 46,567,978 |
| $ | 466 |
| $ | 552,889 |
| $ | (1,441) |
| $ | (237,960) |
| $ | 313,954 |
Adoption of ASU 2016-09 |
| — |
|
| — |
|
| 401 |
|
| — |
|
| (401) |
|
| — |
Adoption of ASC 606 |
| — |
|
| — |
|
| — |
|
| — |
|
| 23,979 |
|
| 23,979 |
Balance, December 31, 2016 as revised |
| 46,567,978 |
|
| 466 |
|
| 553,290 |
|
| (1,441) |
|
| (214,382) |
|
| 337,933 |
Issuance of common stock upon exercise of stock awards |
| 363,603 |
|
| 4 |
|
| 2,793 |
|
| — |
|
| — |
|
| 2,797 |
Issuance of common stock under the Employee Stock Purchase Plan |
| 70,907 |
|
| — |
|
| 936 |
|
| — |
|
| — |
|
| 936 |
Comprehensive loss |
| — |
|
| — |
|
| — |
|
| (367) |
|
| (48,925) |
|
| (49,292) |
Stock-based compensation |
| — |
|
| — |
|
| 13,651 |
|
| — |
|
| — |
|
| 13,651 |
Balance, December 31, 2017 |
| 47,002,488 |
| $ | 470 |
| $ | 570,670 |
| $ | (1,808) |
| $ | (263,307) |
| $ | 306,025 |
Adoption of ASC topic 606 |
| — |
|
| — |
|
| — |
|
| — |
|
| 10,439 |
|
| 10,439 |
Balance, December 31, 2017 as revised |
| 47,002,488 |
| $ | 470 |
| $ | 570,670 |
| $ | (1,808) |
| $ | (252,868) |
| $ | 316,464 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Accumulated |
|
|
|
|
|
| |
|
|
|
|
|
|
| Additional |
| Other |
|
|
|
| Total | |||
|
| Common Stock |
| Paid |
| Comprehensive |
| Accumulated |
| Stockholders’ | |||||||
Stockholders’ Equity |
| Shares |
| Amount |
| in-Capital |
| Loss |
| Deficit |
| Equity | |||||
Balance, December 31, 2015 as originally reported |
| 40,551,039 |
| $ | 405 |
| $ | 424,128 |
| $ | (516) |
| $ | (261,585) |
| $ | 162,432 |
Adoption of ASC Topic 606 |
| — |
|
| — |
|
| — |
|
| — |
|
| 2,479 |
|
| 2,479 |
Balance, December 31, 2015 as revised |
| 40,551,039 |
|
| 405 |
|
| 424,128 |
|
| (516) |
|
| (259,106) |
|
| 164,911 |
Sale of common stock, net of issuance cost |
| 5,272,750 |
|
| 53 |
|
| 119,216 |
|
| — |
|
| — |
|
| 119,269 |
Issuance of common stock upon exercise of stock awards |
| 699,066 |
|
| 7 |
|
| 1,153 |
|
| — |
|
| — |
|
| 1,160 |
Issuance of common stock under the Employee Stock Purchase Plan |
| 45,123 |
|
| 1 |
|
| 544 |
|
| — |
|
| — |
|
| 545 |
Comprehensive income (loss) |
| — |
|
| — |
|
| — |
|
| (925) |
|
| 23,625 |
|
| 22,700 |
Stock-based compensation |
| — |
|
| — |
|
| 7,848 |
|
| — |
|
| — |
|
| 7,848 |
Balance, December 31, 2016 |
| 46,567,978 |
|
| 466 |
|
| 552,889 |
|
| (1,441) |
|
| (235,481) |
|
| 316,433 |
Adoption of ASC Topic 606 |
| — |
|
| — |
|
| — |
|
| — |
|
| 21,500 |
|
| 21,500 |
Balance, December 31, 2016 as revised |
| 46,567,978 |
| $ | 466 |
| $ | 552,889 |
| $ | (1,441) |
| $ | (213,981) |
| $ | 337,933 |
115
Statement of Cash Flows
|
|
|
|
|
|
|
|
|
|
|
| As Reported |
|
|
|
| As Revised | ||
|
| Year Ended |
| Effect of |
| Year Ended | |||
|
| December 31, |
| Adoption of |
| December 31, | |||
|
| 2017 |
| ASC 606 |
| 2017 | |||
Cash flows from operating activities |
|
|
|
|
|
|
|
|
|
Net loss |
| $ | (48,925) |
| $ | 10,439 |
| $ | (38,486) |
Adjustments to reconcile net loss to net cash used in operating activities: |
|
|
|
|
|
|
|
|
|
Depreciation and amortization |
|
| 2,030 |
|
| — |
|
| 2,030 |
Amortization of premium on marketable securities |
|
| 2,845 |
|
| — |
|
| 2,845 |
Stock-based compensation |
|
| 13,651 |
|
| — |
|
| 13,651 |
Abandonment of capitalized intangible assets |
|
| 396 |
|
| — |
|
| 396 |
Loss on disposal of assets |
|
| 83 |
|
| — |
|
| 83 |
Changes in operating assets and liabilities: |
|
|
|
|
|
|
|
|
|
Accounts receivable |
|
| 7,474 |
|
| — |
|
| 7,474 |
Interest receivable |
|
| (293) |
|
| (14) |
|
| (307) |
Prepaid expenses and other assets |
|
| (2,705) |
|
| — |
|
| (2,705) |
Income tax receivable |
|
| (1,524) |
|
| — |
|
| (1,524) |
Other assets |
|
| (161) |
|
| — |
|
| (161) |
Accounts payable |
|
| 2,989 |
|
| — |
|
| 2,989 |
Accrued expenses |
|
| (1,212) |
|
| — |
|
| (1,212) |
Deferred rent |
|
| 589 |
|
| — |
|
| 589 |
Income tax payable |
|
| 91 |
|
| — |
|
| 91 |
Deferred revenue |
|
| (9,011) |
|
| (10,339) |
|
| (19,350) |
Net cash used in operating activities |
|
| (33,683) |
|
| 86 |
|
| (33,597) |
Cash flows from investing activities |
|
|
|
|
|
|
|
|
|
Proceeds from sale and maturities of marketable securities available-for-sale |
|
| 115,757 |
|
| — |
|
| 115,757 |
Purchase of marketable securities |
|
| (76,529) |
|
| — |
|
| (76,529) |
Purchase of intangible assets |
|
| (1,967) |
|
| — |
|
| (1,967) |
Purchase of property and equipment |
|
| (5,311) |
|
| — |
|
| (5,311) |
Issuance of loan |
|
| — |
|
| (86) |
|
| (86) |
Net cash provided by (used in) investing activities |
|
| 31,950 |
|
| (86) |
|
| 31,864 |
Cash flows from financing activities |
|
|
|
|
|
|
|
|
|
Proceeds from issuance of common stock upon exercise of stock awards |
|
| 2,797 |
|
| — |
|
| 2,797 |
Proceeds from issuance of common stock from Employee Stock Purchase Plan |
|
| 936 |
|
| — |
|
| 936 |
Net cash provided by financing activities |
|
| 3,733 |
|
| — |
|
| 3,733 |
Net increase in cash and cash equivalents |
|
| 2,000 |
|
| — |
|
| 2,000 |
Cash and cash equivalents, beginning of period |
|
| 14,528 |
|
| — |
|
| 14,528 |
Cash and cash equivalents, end of period |
| $ | 16,528 |
| $ | — |
| $ | 16,528 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
116
|
| As Reported |
|
|
|
| As Revised | ||
|
| Year Ended |
| Effect of |
| Year Ended | |||
|
| December 31, |
| Adoption of |
| December 31, | |||
|
| 2016 |
| ASC 606 |
| 2016 | |||
Cash flows from operating activities |
|
|
|
|
|
|
|
|
|
Net income |
| $ | 23,625 |
| $ | 21,500 |
| $ | 45,125 |
Adjustments to reconcile net income to net cash provided by operating activities: |
|
|
|
|
|
|
|
|
|
Depreciation and amortization |
|
| 1,466 |
|
| — |
|
| 1,466 |
Amortization of premium on marketable securities |
|
| 2,037 |
|
| — |
|
| 2,037 |
Stock-based compensation |
|
| 7,848 |
|
| — |
|
| 7,848 |
Abandonment of capitalized intangible assets |
|
| 356 |
|
| — |
|
| 356 |
Gain on sale of marketable securities available for sale |
|
| (5) |
|
| — |
|
| (5) |
Changes in operating assets and liabilities: |
|
|
|
|
|
|
|
|
|
Accounts receivable |
|
| (8,572) |
|
| — |
|
| (8,572) |
Interest receivable |
|
| (530) |
|
| (79) |
|
| (609) |
Prepaid expenses and other assets |
|
| (1,700) |
|
| — |
|
| (1,700) |
Other assets |
|
| (40) |
|
| — |
|
| (40) |
Accounts payable |
|
| (2,520) |
|
| — |
|
| (2,520) |
Accrued expenses |
|
| 3,058 |
|
| — |
|
| 3,058 |
Deferred rent |
|
| (89) |
|
| — |
|
| (89) |
Deferred tax liability |
|
| 65 |
|
| — |
|
| 65 |
Deferred revenue |
|
| 69,618 |
|
| (20,800) |
|
| 48,818 |
Net cash provided by operating activities |
|
| 94,617 |
|
| 621 |
|
| 95,238 |
Cash flows from investing activities |
|
|
|
|
|
|
|
|
|
Proceeds from sale and maturities of marketable securities available-for-sale |
|
| 105,505 |
|
| — |
|
| 105,505 |
Purchase of marketable securities |
|
| (316,149) |
|
| — |
|
| (316,149) |
Purchase of intangible assets |
|
| (1,502) |
|
| — |
|
| (1,502) |
Purchase of property and equipment |
|
| (1,507) |
|
| — |
|
| (1,507) |
Proceeds from repayment of (investment in) loan receivable |
|
| — |
|
| (621) |
|
| (621) |
Net cash used in investing activities |
|
| (213,653) |
|
| (621) |
|
| (214,274) |
Cash flows from financing activities |
|
|
|
|
|
|
|
|
|
Proceeds from issuance of common stock upon exercise of stock awards |
|
| 1,160 |
|
| — |
|
| 1,160 |
Proceeds from issuance of common stock from Employee Stock Purchase Plan |
|
| 545 |
|
| — |
|
| 545 |
Proceeds from issuance of common stock |
|
| 126,546 |
|
| — |
|
| 126,546 |
Common stock issuance costs |
|
| (7,277) |
|
| — |
|
| (7,277) |
Net cash provided by financing activities |
|
| 120,974 |
|
| — |
|
| 120,974 |
Net increase in cash and cash equivalents |
|
| 1,938 |
|
| — |
|
| 1,938 |
Cash and cash equivalents, beginning of period |
|
| 12,590 |
|
| — |
|
| 12,590 |
Cash and cash equivalents, end of period |
| $ | 14,528 |
| $ | — |
| $ | 14,528 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
117
13. Subsequent Event
Genentech Agreement
In February 2019, the Company entered into a collaboration and license agreement (the Genentech Agreement) with Genentech, Inc. and F. Hoffmann La-Roche Ltd. (collectively, Genentech) for the development and commercialization of novel IL-15 Collaboration Products, including XmAb24306, an IL-15/IL15Rα cytokine complex engineered with the Company’s bispecific Fc and Xtend technologies. The Company’s IL-15 bispecific cytokine platform provides a more druggable version of IL-15 with potentially superior tolerability, slower receptor-mediated clearance and a prolonged half-life, and is intended for development with a wide-range of combination agents due to its proposed mechanism of activating tumor-killing immune cells.
Under the terms of the Genentech Agreement, Genentech received an exclusive worldwide license to XmAb24306 and other Collaboration Products, including any new IL-15 programs identified during the joint research collaboration. The Company will receive a non-refundable upfront payment of $120 million after the Genentech Agreement becomes effective and is eligible to receive up to an aggregate of $160 million in clinical milestone payments for each Collaboration Product that advances to Phase 3 clinical trials. The Company is eligible to receive a 45% share of net profits for sales of XmAb24306 and other Collaboration Products, while also sharing in the net losses at the same percentage rate. The parties will also jointly share development and commercialization costs at the same percentage rate, while Genentech will bear launch costs entirely. The profit/cost share is subject to ratchet at the Company’s discretion and convertible to a royalty under certain circumstances. The Company and Genentech will also conduct joint research activities for a two-year period to discover additional IL-15 candidates developed from the Company’s cytokine and bispecific Fc technologies. The Company will receive a $20 million development milestone for each new Collaboration Product that is identified from the research efforts and advances into a Phase 1 clinical trial.
The Genentech Agreement is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act, and closing is expected to occur in the first quarter of 2019.
Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
Not applicable.
Evaluation of Disclosure Controls and Procedures
Our management, Chief Executive Officer and Chief Financial Officer, evaluated the effectiveness of our disclosure controls and procedures as of December 31, 2018.2020. The term "disclosure controls and procedures," as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act, means controls and other procedures of a company that are designed to ensure that information required to be disclosed by us in the reports that we file or submit under the
112
Exchange Act is recorded, processed, summarized and reported within the time periods specified in the SEC's rules and forms and that such information is accumulated and communicated to our management, including our Chief Executive Officer and Chief Financial Officer, as appropriate, to allow timely decisions regarding required disclosure. Based on this evaluation our Chief Executive Officer and Chief Financial Officer concluded that our disclosure controls and procedures were effective as of December 31, 20182020 at the reasonable assurance level.
118
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 Rule 13a-15(f) and 15d-15(f) under the Securities Exchange Act of 1934, as amended). Our management, Chief Executive Officer and Chief Financial Officer, assessed the effectiveness of our internal control over financial reporting as of December 31, 2018.2020. In making this assessment, our management used the criteria set forth by the Committee of Sponsoring Organizations of the Treadway Commission (2013 Framework) (COSO) in Internal Control—Integrated Framework. Based on that assessment and using the COSO criteria, our management, Chief Executive Officer and Chief Financial Officer have concluded that, as of December 31, 2018,2020, our internal control over financial reporting was effective.
Changes in Internal Control over Financial Reporting
There has been no change in our internal control over financial reporting during the year ended December 31, 2018,2020, that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting.
Inherent Limitations of Controls
Management does not expect that our disclosure controls and procedures or our internal control over financial reporting will prevent or detect all error and all fraud. Controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives, and management necessarily applies its judgment in evaluating the cost-benefit relationship of possible controls and procedures. Because of the inherent limitations in all control systems, no evaluation of controls can provide absolute assurance that all control issues and instances of fraud, if any, within the Company have been detected. These inherent limitations include the realities that judgments in decision-making can be faulty and that breakdowns can occur because of a simple error or mistake. Additionally, controls can be circumvented by the individual acts of some persons, by collusion of two or more people, or by management override of the controls. The design of any system of controls also is based in part upon certain assumptions about the likelihood of future events, and there can be no assurance that any design will succeed in achieving its stated goals under all potential future conditions. Over time, controls may become inadequate because of changes in conditions or deterioration in the degree of compliance with the policies or procedures. Because of the inherent limitations in a cost-effective control system, misstatements due to error or fraud may occur and not be detected.
Attestation in Internal Control over Financial Reporting
RSM US LLP, our independent registered public accounting firm, has audited our financial statements for the year ended December 31, 20182020 and has issued an audit report on the effectiveness of the Company’s internal control over financial reporting as of December 31, 2018,2020, which is included in Item 8 of this Annual Report on From 10-K.Report.
Not applicable.
119113
PART III
Item 10.10. Directors, Executive Officers and Corporate Governance
We have adopted a code of ethics for directors, officers (including our principal executive officer, principal financial officer and principal accounting officer) and employees, known as the Code of Business Conduct and Ethics. The Code of Business Conduct and Ethics is available on our website at http://www.xencor.com under the Corporate Governance section of our Investor Relations page. We will promptly disclose on our website (i) the nature of any amendment to the policy that applies to our principal executive officer, principal financial officer, principal accounting officer or controller, or persons performing similar functions and (ii) the nature of any waiver, including an implicit waiver, from a provision of the policy that is granted to one of these specified individuals that is required to be disclosed pursuant to SEC rules and regulations, the name of such person who is granted the waiver and the date of the waiver.
The other information required by this item and not set forth below will be set forth in our 20192021 Annual Meeting of Stockholders (Proxy Statement) to be filed with the SEC within 120 days after the end of the fiscal year ended December 31, 2018,2020 and is incorporated herein by reference.
Audit Committee
The information required by this item will be set forth in the Proxy Statement and is incorporated herein by reference.
Item The information required by this item will be set forth in the Proxy Statement and is incorporated herein by reference.11.11. Executive Compensationn
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
The information required by this item will be set forth in the Proxy Statement and is incorporated herein by reference.
Item 13. Certain Relationships and Related Transactions, and Director Independence
The information required by this item will be set forth in the Proxy Statement and is incorporated herein by reference.
Item 14. Principal Accounting Fees and Services
The information required by this item will be set forth in the Proxy Statement and is incorporated herein by reference.
The information required by this item will be set forth in the Proxy Statement and is incorporated herein by reference.
Item 13. Certain Relationships and Related Transactions, and Director Independence
The information required by this item will be set forth in the Proxy Statement and is incorporated herein by reference.
Item 14. Principal Accounting Fees and Services
The information required by this item will be set forth in the Proxy Statement and is incorporated herein by reference.
120114
1.Financial Statements. We have filed the following documents as part of this Annual Report:
| |
| Page |
Report of Independent Registered Public Accounting Firm (RSM US LLP) | 76 |
79 | |
80 | |
81 | |
82 | |
83 |
2.Financial Statement Schedules. All schedules have been omitted because they are not applicable or required, or the information required to be set forth therein is included in the Financial Statements or notes thereto included in Item 8 of this Annual Report on Form 10‑K.10-K.
3.Exhibits.
Exhibit | Description | |
|
| |
| ||
| | |
3.2 | | |
| | |
4.1 | | |
| | |
4.2* | | |
| | |
4.3 | | |
| | |
10.1* | | |
| | |
10.2* | | |
| | |
10.3* | | |
| | |
115
121
10.5* | | |
| ||
| | |
| | |
| ||
| ||
| ||
| ||
| ||
| | |
| | |
| ||
| | |
| | |
| | |
| | |
122
| ||
| | |
| | |
| | |
| | |
| ||
| ||
| | |
10.12 | | |
| | |
10.13 | ||
| ||
| | |
| | |
| | |
| | |
| ||
| | |
| | |
| | |
116
123
| ||
| | |
| | |
| | |
10.29† | ||
| | |
10.20 | | |
10.21 | | |
10.22† | ||
| ||
| | |
10.23* | | |
| | |
10.24* | | |
| | |
10.25* | | |
| | |
10.26 | | |
| | |
10.27 | | |
| | |
10.28 | | |
| | |
10.29 | | |
| | |
10.30 | | |
| | |
10.31 | |
117
| | |
10.32 | | |
| | |
10.33 | | |
| | |
10.34 | | |
| | |
23.1 | | Consent of Independent Registered Public Accounting Firm (RSM US LLP). |
| | |
31.1 | | |
| | |
31.2 | | |
| | |
32.1** | | |
| | |
32.2** | |
| ||
101.INS | | XBRL Instance |
101.SCH | | XBRL Taxonomy Extension Schema Document. |
101.CAL | | XBRL Taxonomy Extension Schema Document. |
101.DEF | | XBRL Taxonomy Extension Definition Linkbase Document. |
101.LAB | | XBRL Taxonomy Extension Label Linkbase Document. |
101.PRE | | XBRL Taxonomy Extension Presentation Linkbase Document. |
| | |
104 | | 104 Cover Page Interactive Data File (formatted as Inline XBRL and contained in Exhibit 101) |
† We have received confidential treatment for certain portions of this agreement, which have been omitted and filed separately with the SEC pursuant to Rule 406 under the Securities Act of 1933, as amended.
124
* Indicates management contract or compensatory plan.
** These certifications are being furnished solely to accompany this annual report pursuant to 18 U.S.C. Section 1350, and are not being filed for purposes of Section 18 of the Securities Exchange Act of 1934 and are not to be incorporated by reference into any filing of the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
None.
125118
SIGNATURES
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the Company has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| Xencor, Inc. | |
| | |
Date: February | By: | /s/ Bassil I. Dahiyat, Ph.D. |
Bassil I. Dahiyat, Ph.D. | ||
POWER OF ATTORNEY
KNOW ALL MEN BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Bassil I. Dahiyat, Ph.D. and John J. Kuch, and each of them, his true and lawful attorneys‑in‑fact,attorneys-in-fact, each with full power of substitution, for him in any and all capacities, to sign any amendments to this Annual Report on Form 10‑K10-K and to file the same, with exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, hereby ratifying and confirming all that each of said attorneys‑in‑factattorneys-in-fact or their substitute or substitutes may do or cause to be done by virtue hereof.
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of the Company and in the capacities and on the dates indicated.
Signature | | Title | | Date |
| | | | |
/s/ BASSIL I. DAHIYAT, PH.D. | | Director, President & Chief Executive Officer (Principal Executive Officer) | | February |
Bassil I. Dahiyat, Ph.D. | | | ||
| | | | |
/s/ JOHN J. KUCH | | Sr. Vice President | | February |
John J. Kuch | | | ||
| | | | |
/s/ A. BRUCE MONTGOMERY, M.D. | | Director | | February |
A. Bruce Montgomery, M.D. | | | ||
| | | | |
/s/ KURT GUSTAFSON | | Director | | February |
Kurt Gustafson | | | ||
| | | | |
/s/ YUJIRO S. HATA | | Director | | February |
Yujiro S. Hata | | | ||
| | | | |
/s/ KEVIN C. GORMAN, PH.D. | | Director | | February |
Kevin C. Gorman, Ph.D. | | | | |
| | | | |
/s/ RICHARD RANIERI | | Director | | February |
Richard Ranieri | | | | |
| | | | |
/s/ ELLEN G. FEIGAL, M.D. | | Director | | February |
Ellen G. Feigal, M.D. | | | ||
| | | | |
/s/ DAGMAR ROSA-BJORKESON | | Director | | February 23, 2021 |
Dagmar Rosa-Bjorkeson | | |
126119