Navidea Biopharmaceuticals, Inc. (“Navidea,” the “Company,” “our” or “we”), a Delaware corporation (NYSE American: NAVB), is a biopharmaceutical company focused on the development and commercialization of precision immunodiagnostic agents and immunotherapeutics. Navidea is developing multiple precision-targeted products based on our Manocept™ platform to enhance patient care by identifying the sites and pathways of undetected disease and enable better diagnostic accuracy, clinical decision-making and targeted treatment.

Navidea’s Manocept platform is predicated on the ability to specifically target the CD206 mannose receptor expressed on activated macrophages. The Manocept platform serves as the molecular backbone of Tc99m tilmanocept, the first product developed and commercialized by Navidea based on the platform.

On March 3, 2017, pursuant to an Asset Purchase Agreement dated November 23, 2016 (the “Purchase Agreement”), the Company completed its previously announced sale to Cardinal Health 414, LLC (“Cardinal Health 414”) of its assets used, held for use, or intended to be used in operating its business of developing, manufacturing and commercializing a product used for lymphatic mapping, lymph node biopsy, and the diagnosis of metastatic spread to lymph nodes for staging of cancer (the “Business”), including the Company’s radioactive diagnostic agent marketed under the Lymphoseek^® trademark for current approved indications by the U.S. Food and Drug Administration (“FDA”) and similar indications approved by the FDA in the future (the “Product”), in Canada, Mexico and the United States (the “Territory”) (giving effect to the License-Back described below and excluding certain assets specifically retained by the Company) (the “Asset Sale”). Such assets sold in the Asset Sale consist primarily of, without limitation, (i) intellectual property used in or reasonably necessary for the conduct of the Business, (ii) inventory of, and customer, distribution, and product manufacturing agreements related to, the Business, (iii) all product registrations related to the Product, including the new drug application approved by the FDA for the Product and all regulatory submissions in the United States that have been made with respect to the Product and all Health Canada regulatory submissions and, in each case, all files and records related thereto, (iv) all related clinical trials and clinical trial authorizations and all files and records related thereto, and (v) all rights, title and interest in and to the Product, as specified in the Purchase Agreement (the “Acquired Assets”).

In connection with the closing of the Asset Sale, the Company entered into a License-Back Agreement (the “License-Back”) with Cardinal Health 414. Pursuant to the License-Back, Cardinal Health 414 granted to the Company a sublicensable (subject to conditions) and royalty-free license to use certain intellectual property rights included in the Acquired Assets and owned by Cardinal Health 414 as of the closing of the Asset Sale to the extent necessary for the Company to (i) on an exclusive basis, subject to certain conditions, develop, manufacture, market, sell and distribute new pharmaceutical and other products that are not Competing Products (as defined in the License-Back), and (ii) on a non-exclusive basis, develop, manufacture, market, sell and distribute the Product throughout the world other than in the Territory. Subject to the Company’s compliance with certain restrictions in the License-Back, the License-Back also restricts Cardinal Health 414 from using the intellectual property rights included in the Acquired Assets to develop, manufacture, market, sell, or distribute any product other than the Product or other product that (a) accumulates in lymphatic tissue or tumor-draining lymph nodes for the purpose of (1) lymphatic mapping or (2) identifying the existence, location or staging of cancer in a body, or (b) provides for or facilitates any test or procedure that is reasonably substitutable for any test or procedure provided for or facilitated by the Product. Pursuant to the License-Back and subject to rights under existing agreements, Cardinal Health 414 was given a right of first offer to market, sell and/or market any new products developed from the intellectual property rights licensed by Cardinal Health 414 to the Company by the License-Back.

As part of the Asset Sale, the Company and Cardinal Health 414 also entered into ancillary agreements providing for transitional services and other arrangements. The Company amended and restated its license agreement with The Regents of the University of California, San Diego (“UCSD”) pursuant to which UCSD granted a license to the Company to exploit certain intellectual property rights owned by UCSD and, separately, Cardinal Health 414 entered into a license agreement with UCSD pursuant to which UCSD granted a license to Cardinal Health 414 to exploit certain intellectual property rights owned by UCSD for Cardinal Health 414 to sell the Product in the Territory.

Upon closing of the Asset Sale, the Supply and Distribution Agreement, dated November 15, 2007, as amended, between Cardinal Health 414 and the Company was terminated and, as a result, the provisions thereof are of no further force or effect (other than any indemnification, payment, notification or data sharing obligations which survive the termination).

Other than Tc99m tilmanocept, which the Company has a license to distribute outside of Canada, Mexico and the United States, none of the Company’s drug product candidates have been approved for sale in any market.

Our business is focused on two primary types of drug products: (i) diagnostic substances, including Tc99m tilmanocept and other diagnostic applications of our Manocept platform, and ~~NAV4694, and~~ (ii) therapeutic development programs, including therapeutic applications of our Manocept ~~platform and all development programs undertaken by Macrophage Therapeutics, Inc.~~platform. See Note 1815 to the accompanying consolidated financial statements for more information about our business segments.

We were originally incorporated in Ohio in 1983 and reincorporated in Delaware in 1988. From inception until January 2012, we operated under the name Neoprobe Corporation. In January 2012, we changed our name to Navidea Biopharmaceuticals, Inc. in connection with both the sale of our medical device business and our strategic repositioning as a precision medicines company focused on the development and commercialization of precision diagnostic and therapeutic pharmaceuticals.

Since our inception, the majority of our efforts and resources have been devoted to the research and clinical development of radiopharmaceutical technologies primarily related to the intraoperative diagnosis and treatment of cancers. From the late 1990’s through 2011, we also devoted substantial effort towards the development and commercialization of medical devices, including a line of handheld gamma detection devices which was sold in 2011 and a line of blood flow measurement devices which we operated from 2001 through 2009.

~~From our inception through August~~Beginning in late 2011, ~~we manufactured a line of gamma radiation detection medical devices called the neoprobe~~^® GDS system (the “GDS Business”). We sold the GDS Business to Devicor Medical Products, Inc. (“Devicor”) in August 2011. Following the sale of the GDS business and the subsequent strategic repositioning as a precision medicines company, the Company in-licensed two neuro-tracer product candidates, NAV4694 and NAV5001. The Company ~~progressed~~advanced the development of both product candidates over the course of 2012 through 2014, moving both into Phase 3 clinical trials. However, in May 2014, the Navidea Board of Directors announced that the Company would restructure its development efforts to focus on cost effective development of the Manocept platform and divest its neuro-tracer product candidates. In April 2015, the Company entered into an agreement with Alseres Pharmaceuticals, Inc. (“Alseres”) to terminate the NAV5001 ~~sub-license~~sublicense agreement. In January 2021, the Company executed an agreement with Alseres and LikeMinds, Inc. (“LikeMinds”), pursuant to which Alseres assigned its obligations under the previous sublicense and termination agreements, including certain milestone and royalty payments, to LikeMinds. In April 2018, the Company executed an agreement to provide Meilleur Technologies, Inc. (“Meilleur”) worldwide rights to conduct research using NAV4694, as well as an exclusive license for the development and commercialization of NAV4694 in Australia, Canada, China, and Singapore. Meilleur also has an option to commercialize worldwide.

In December 2014, we announced the formation of a new business unit to further explore therapeutic applications for the Manocept platform, which was incorporated as Macrophage Therapeutics, Inc. (“MT”) in January 2015 as a majority-owned subsidiary of Navidea. Navidea also granted MT an exclusive sublicense for certain therapeutic applications of the Manocept technology. MT has developed processes for producing the first two therapeutic Manocept immuno-constructs, MT-1002, designed to specifically target and kill activated CD206+ macrophages by delivering doxorubicin, and MT-2002, designed to inhibit the inflammatory activity of activated CD206+ macrophages by delivering a potent anti-inflammatory agent. MT has contracted with independent facilities to produce sufficient quantities of the MT-1002 and MT-2002 agents along with the concomitant analytical standards, to provide material for planned preclinical animal studies and future clinical trials.

In August 2018, the Company entered into an agreement (the “Agreement”) with Dr. Michael Goldberg related to his resignation from his positions as an executive officer and a director of Navidea. Among other things, the Agreement provided that Dr. Goldberg would become Chief Executive Officer of MT, and that MT would redeem all of Dr. Goldberg’s MT preferred stock and issue to Dr. Goldberg MT super voting common stock equal to 5% of the outstanding shares of MT, subject to execution of Definitive Agreements. As of the date of filing of this Annual Report on Form 10-K, the Definitive Agreements have not yet been signed.

On February 11, 2019, Dr. Goldberg represented to the MT Board that he had, without MT Board or shareholder approval, created a subsidiary of MT, transferred all of the assets of MT into the subsidiary, and then issued himself stock in the subsidiary. On February 19, 2019, Navidea notified MT that it was terminating the sublicense effectiveEffective March 1, 2019, ~~because MT became insolvent in violation of~~Navidea terminated the sublicense ~~agreement. On February 20, 2019,~~to MT in accordance with its terms due to MT’s insolvency. Since then, Navidea has continued the ~~Board~~development of Directors of MT removed Dr. Goldberg as President and Chief Executive Officer of MT and from any other office of MT to which he may have been appointed or in which he was serving. Dr. Goldberg remains a member oftherapeutic products based on the MT Board, together with Michael Rice and Dr. Claudine Bruck. Mr. Rice and Dr. Bruck remain members of the board of directors of Navidea. The MT Board then appointed Mr. Latkin to serve as President and Chief Executive Officer of MT.

On February 20, 2019, Navidea filed a complaint against Dr. Goldberg in the United States District Court for the Southern District of New York, alleging breach of the Agreement, as well as a breach of the covenant of good faith and fair dealing and to obtain a declaratory judgment that Navidea’s performance under the Agreement is excused and that Navidea is entitled to terminate the Agreement as a result of Dr. Goldberg’s actions. Also on February 20, 2019, MT initiated a suit against Dr. Goldberg in the Court of Chancery of the State of Delaware, alleging, among other things, breach of fiduciary duty as a director and officer of MT and conversion, and to obtain a declaratory judgment that the transactions Dr. Goldberg caused MT to enter into are void. On March 13, 2019, the Court of Chancery entered an order maintaining status quo, which provided, among other things, that MT’s board of directors may authorize any act or transaction on behalf of the Company, and that without prior written authorization of the MT board, Dr. Goldberg shall not hold himself out as CEO of MT or purport to act or authorize any action on behalf of MT except as authorized by the MT board.Manocept platform.

On March 7, 2019, Dr. Goldberg filed a complaint against Navidea and MT in the United States District Court for the Southern District of New York. The Complaint alleges a breach of contract claim against both Navidea and MT for failure to pay to Dr. Goldberg funds allegedly due to him under the Promissory Note, dated July 25, 2012, made by the Company in favor of Platinum-Montaur Life Sciences LLC (the “Platinum Note”). The Complaint further alleges a breach of contract claim against Navidea due to Navidea’s failure to issue 23.5 million shares to Dr. Goldberg, to issue MT Super Voting Common Stock, by removing Dr. Greene from the MT Board of Directors, by appointing Mr. Rice and Dr. Bruck to the MT Board of Directors, and by terminating Dr. Goldberg as CEO of MT.

Our primary development efforts over the last several years were focused on diagnostic products, including ~~Lymphoseek~~Tc99m tilmanocept, which ~~was sold~~the Company has a license to ~~Cardinal Health 414 in March 2017.~~distribute outside of Canada, Mexico and the United States. Our more recent initiatives have been focused ~~exclusively~~ on diagnostic and therapeutic line extensions based on our Manocept platform.

During the ongoing COVID-19 global pandemic, the Company’s primary concern is the safety of its employees, the employees of its clinical trial sites, and the patients enrolled in its clinical trials. The Company is working hard to mitigate any safety risk along with any long-term impact on its clinical development programs. We do not believe there has been a significant impact to the Company’s clinical development and regulatory timelines resulting from the ongoing COVID-19 global pandemic. However, the COVID-19 outbreak delayed enrollment in our NAV3-32 clinical study in the United Kingdom due to national COVID-19-related shutdowns. In addition, the regulatory approval process in India was delayed by the impact of COVID-19 in that country.

As brief overview of recent developments in the Company’s diagnostics area (additional details in following sections), Navidea has completed the Phase 2b clinical trial (NAV3-31) evaluating imaging repeatability, reproducibility, and stability, as well as the capacity of Tc99m tilmanocept imaging to serve as an early predictor of treatment efficacy of anti-tumor necrosis factor alpha (“TNFα”) therapy in patients with moderate to severe Rheumatoid Arthritis (“RA”). In addition, the Company has completed enrollment into a Phase 2b clinical trial (NAV3-35) designed to accrue hand and wrist planar and single photon emission computed tomography/computed tomography (“SPECT/CT”) images from healthy subjects (with SPECT/CT imaging also done on a small group of RA patients) so that Navidea can complete a normative database in support of its RA imaging commercial product development. The Company’s recently launched pivotal Phase 3 trial for RA (NAV3-33) is the next step in the development plan for indications in RA. The additional Phase 2b trial (NAV3-32) correlating Tc99m tilmanocept uptake in RA-involved joints with CD206 immunohistochemistry findings from synovial biopsies is actively recruiting. In addition, the investigator-initiated Phase 2 cardiovascular (“CV”) study was completed at Massachusetts General Hospital and a manuscript has been submitted by the investigators. Results of this study provided to date have paralleled data in our earlier published article, and these data are supportive of Navidea’s hypothesis that tilmanocept can provide marked signal to background in a host of CV disease applications.

Navidea’s Manocept platform is predicated on the ability to specifically target the ~~CD206~~ mannose receptor (CD206) expressed primarily on activated macrophages. This flexible and versatile platform serves as a molecular ~~engine~~backbone for purpose-built targeted imaging molecules that may significantly impact patient care by providing enhanced diagnostic accuracy, clinical decision-making, and target-specific treatment. This CD206-targeted drug platform is applicable to a range of diagnostic modalities, including ~~single photon emission computed tomography (“SPECT”),~~SPECT, positron emission tomography (“PET”), gamma-scanning ~~(both imaging and topical)~~ and intra-operative and/or optical-fluorescence detection, as well as delivery of therapeutic compounds that target macrophages and their role in a variety of immune- and inflammation-involved diseases. The ~~FDA-approved~~United States Food and Drug Administration (“FDA”)-approved sentinel node/lymphatic mapping agent, Tc99m tilmanocept, is representative of the ability to successfully exploit this mechanism to develop powerful new products and to expand this technology into additional diagnostic and therapeutic applications.

Activated macrophages play important roles in many disease states and are an emerging target in many diseases where diagnostic uncertainty exists. Impairment of the macrophage-driven disease mechanisms is an area of increasing and proven focus in medicine. The number of people affected by all the inflammatory diseases combined is estimated at more than 40 million in the United States and up to 700 million worldwide, making macrophage-mediated diseases an area of remarkable clinical importance. There are many recognized disorders having macrophage involvement, including ~~rheumatoid arthritis (“RA”),~~RA, atherosclerosis/vulnerable plaque, nonalcoholic steatohepatitis, ~~(“NASH”),~~ inflammatory bowel disease, systemic lupus erythematosus, cancer generally including Kaposi’s sarcoma (“KS”), ~~leishmaniosis,~~leishmaniasis, and others that span general clinical areas in ~~oncology,~~cancer immunology, autoimmunity, infectious diseases, cardiology, ~~CNS~~central nervous system diseases, and inflammation. For the near term, we have selected target diseases that may, if successfully developed, benefit from this technology.

The Company has developed processes for producing the first two therapeutic Manocept immuno-construct series, the Manocept doxorubicin (“MAN-DOX”) series, which is designed to specifically target and kill or modify activated CD206+ macrophages by delivering doxorubicin, and the Manocept dexamethasone (“MAN-DEX”) series, which is designed to inhibit the inflammatory activity of activated CD206+ macrophages by delivering a potent anti-inflammatory agent, dexamethasone. We have contracted with independent facilities to improve chemical syntheses and to produce sufficient quantities of the MAN-DOX series and MAN-DEX series agents, along with the concomitant analytical standards, to provide material for current and planned preclinical animal studies and future clinical trials. Evaluation of an advanced MAN-DOX construct has been successfully evaluated in both human macrophage cell culture assays and in various syngeneic mouse models of cancer. Similar evaluations of an advanced MAN-DEX construct are currently ongoing.

Two Tc99m tilmanocept dose escalation studies in RA have been completed. The first study was completed and included 18 subjects (nine with active disease and nine healthy subjects) dosed subcutaneously (“SC”) with 50 and 200 µg/2mCi Tc99m tilmanocept (ClinicalTrials.gov NCT02683421). The results of this study were presented at five international meetings, including Biotechnology Innovation Organization, ~~(“BIO”),~~ Society of Nuclear Medicine and Molecular Imaging (“SNMMI”), and The American College of Rheumatology (“ACR”). In addition, based on completion of extensive preclinical dosing studies pursuant to our dialog with the FDA, we have completed a Phase 1/2 study involving intravenous (“IV”) dosing of 39 subjects with IV-administered Tc99m tilmanocept (ClinicalTrials.gov NCT02865434). In conjunction with this study, we ~~have~~ completed pharmacokinetic, pharmacodynamics and radiation dosimetry phases in human subjects as well. The majority of the costs of these studies ~~have been~~were supported through a Small Business Innovation Research (“SBIR”) grant (NIH/NIAMSD Grant 1 R44 AR067583-01A1). Results of the Phase 1/2 study were presented at the June 2018 and June 2019 SNMMI meetings, the 2018 European League Against Rheumatism (“EULAR”) meeting and the 2018 ACR meeting. These studies have been combined and submitted for peer review publication and full published results will follow.

The Phase 1/2 study enrolled subjects with active, moderate-to-severe RA, and healthy controls. Results from the completed trial demonstrated that Tc99m tilmanocept is well-tolerated with no serious adverse events, adverse drug reactions, or drug-related adverse events observed. Additionally, static planar images revealed joint-specific Tc99m tilmanocept localization in RA subjects to disease-involved joints of the shoulders, knees, hands, and feet, but no joint-specific localization in healthy control subjects, revealing potentially significant immunodiagnostic information about CD206-expressing synovial macrophage involvement in RA. An optimal imaging time window post-Tc99m tilmanocept IV administration, as well as optimal dosing, were also determined.

In April 2019, the Company received feedback from the FDA regarding the Company’s planned clinical studies to evaluate joint disease in patients with RA and monitor patient response to therapy. The Company’s proposed RA studies were discussed with the FDA during an in-person meeting and through follow-up collaborative efforts. The FDA communicated that the first study, a Phase 2b trial, was aligned with expectations for the studies and that they would continue to work with Navidea as the Company progressed into the second Phase 2b trial correlating Tc99m tilmanocept uptake in RA-involved joints with CD206 immunohistochemistry findings from synovial biopsies and into the planned Phase 3 clinical trial.

In May 2019, we began enrolling patients into the first Phase 2b study, (NAV3-31), entitled “Evaluation of the Precision and Sensitivity of Tilmanocept Uptake Value (“TUV”) on Tc99m Tilmanocept Planar Imaging” (ClinicalTrials.gov MCT03938636). This study, since completed, provided confirmatory support necessary to initiate Navidea’s Phase 3 study program. In October 2019, the Company performed its first interim analysis of this trial, covering subjects enrolling into Arms 1 and 2. The results of this interim analysis were in line with the Company’s hypotheses that Tc99m tilmanocept can provide robust, stable imaging in healthy subjects as well as in patients with active RA, and provide the fundamental information needed to keep moving forward into the Phase 3. A summary of these results was presented at the 2020 EULAR meeting. In May 2020, the Company announced the results of its second interim analysis, covering Arm 3 of the trial. This Arm mirrored the upcoming Phase 3 in design and provided information relevant for sample size calculation for the Phase 3 as well as support for the hypothesis that Tc99m tilmanocept imaging can provide an early indicator of treatment efficacy of anti-TNFα therapeutics. These interim results were presented at the 2020 ACR meeting. In June 2020, the Company announced full enrollment into this trial, with imaging events completed in each patient enrolled in Arm 3.

In February 2021, the Company submitted its formal briefing book to the FDA, containing detailed analysis and discussion of the Company’s then-ongoing Phase 2b study (NAV3-31) and prior studies in RA as well as the design and statistical analysis plan for the proposed Phase 3 for FDA comment. Following the feedback received from the FDA at the end of March 2021, the Company continued to work toward completing the analysis of the full NAV3-31 trial dataset and submitted the resultant briefing book containing the results of this analysis in preparation for the standard End-of-Phase 2 Type B meeting, which took place on September 1, 2021. The Company had a constructive meeting with the FDA and, based on the discussion in this meeting and follow-up communication, has made agreed-upon modifications to the trial design for the Phase 3 study (NAV3-33). The Company submitted the modified protocol back to the FDA and initiated the study in December 2021. Following additional feedback from the FDA, the Company made modifications to several of the objectives. Enrollment into the Phase 3 study has begun. The pivotal Phase 3 study program will determine Tc99m tilmanocept’s capability to serve as an early predictor of treatment response to anti-TNFα therapy in patients with RA.

In collaboration with researchers at Massachusetts General Hospital, Navidea has completed ~~one and initiated a second~~two investigator-initiated clinical ~~study~~studies evaluating Tc99m tilmanocept’s ability to enable imaging of atherosclerotic plaques. Results of these studies provide strong preliminary evidence of the potential of Tc99m tilmanocept to accumulate specifically in and enable imaging of non-calcified atherosclerotic plaques. Non-calcified atherosclerotic plaques include plaques with morphologies indicating a high risk of rupture. Rupture of such plaques causes myocardial infarctions (heart attacks) and a significant portion of ischemic strokes. The studies compared aortic Tc99m tilmanocept uptake imaged by SPECT/CT in clinically asymptomatic subjects with intermediate Framingham Risk Scores (“FRS”) who were infected with Human Immunodeficiency Virus (“HIV”) as compared to healthy, uninfected, FRS and age-matched subjects. Tc99m tilmanocept SPECT/CT images were compared to aortic images of the same subjects obtained by contrast enhanced coronary computed tomography angiography and/or [18F]NaF PET/CT.

A nine-subject study to evaluate diagnostic imaging of emerging atherosclerosis plaque with the Tc99m tilmanocept product dosed ~~subcutaneously is complete~~SC was performed (ClinicalTrials.gov NCT02542371). The results of this study were presented at two major international meetings (Conference on Retroviruses and Opportunistic Infections ~~(“CROI”)~~ and SNMMI, 2017) and published in early release in the Journal of Infectious Diseases in January 2017 (published in the circulated version, Journal of Infectious Diseases (2017) 215 (8): 1264-1269), confirming that the Tc99m tilmanocept product can both quantitatively and qualitatively target non-calcified plaque in the aortic arch of Acquired Immunodeficiency Syndrome (“AIDS”) patients (supported by NIH/NHLBI Grant 1 R43 HL127846-01). This study was later expanded to include up to 31 participants, and has achieved full enrollment, with a manuscript submitted.

~~We have also commenced a~~A second ~~Phase1/~~Phase 1/2 investigator-initiated study in cooperation with Massachusetts General Hospital in subjects with HIV was initiated that ~~expands~~expanded the original study in both the scope of the drug administration as well as the diagnostic assessment of the subjects. This study ~~will enroll up to 24~~enrolled both AIDS subjects and healthy controls in imaging non-calcified plaque using ~~IV-administered~~IV and SC-administered Tc99m tilmanocept and will expand the initial investigation to the assessment of aortic plaque as well as carotid and coronary arteries. Initial analysis suggested that the SC route of administration led to superior signal-to-background in areas of non-calcified plaque. These results are being further assessed.

Navidea has also been awarded a $225,000 phase 1 Small Business Technology Transfer grant (1R41HL147640-01A1) entitled Gallium 68 Tilmanocept for PET Imaging of Atherosclerosis Plaques. This grant supports a research collaboration between Navidea and Dr. Suzanne Lapi of the University of Alabama Birmingham evaluating a mouse model of atherosclerosis. This work has as its aim the evaluation of [68]gallium tilmanocept and various next generation imaging agents for visualizing plaques. Activities began in the fourth quarter of 2019. As of January 2022, all images ~~from this study are currently being evaluated.~~have been acquired with efforts now focused on data analyses.

KS is a serious and potentially life-threatening illness, which in the United States occurs disproportionately in persons infected with HIV and in organ transplant patients. The prognosis for patients with treatment-resistant KS is poor with high probabilities for mortality and greatly diminished quality of life. We initiated and completed a study of KS in 2015 (ClinicalTrials.gov NCT022201420), and received additional funding from the National Institutes of Health (“NIH”) in 2016 to continue diagnostic studies in this disease. The new support not only continues the imaging of the cutaneous form of this disease but expands this to imaging of visceral disease via IV administration of Tc99m tilmanocept (NIH/NCI 1 R44 CA192859-01A1; ClinicalTrials.gov NCT03157167). This now-escalated study includes a pathology/biopsy component as well as an imaging component to determine pathology concordance with image assessment. We received Institutional Review Board approval of the clinical protocol weand initiated a Phase 1/2 clinical study in KS in ~~2017,~~2017. This trial has completed enrollment and ~~the trial is currently~~imaging. Data and image analysis for this study are ongoing.

~~Colorectal Cancer (“CRC”~~Tuberculosis (“TB”) ~~and Synchronous Liver Metastases~~

~~During~~In April 2019, the ~~first quarter of 2017, we initiated an imaging study in subjects with CRC~~Company announced that Professor Mike Sathekge, MBChB, M. Med (Nuclear Medicine), PhD, Professor and liver metastases via IV administration of Tc99m tilmanocept. This study was supported through a SBIR grant (NIH/NCI 1 R44 CA1962783-01A1; ClinicalTrials.gov NCT03029988). The trial intended to enroll up to 12 subjects with dose modification. After an interim analysisHead of the ~~first three completed subjects,~~Department of Nuclear Medicine in the Faculty of Health Sciences at the University of Pretoria/Steve Biko Academic Hospital, planned to initiate a ~~decision was made to not continue~~comparative study evaluating the use of tilmanocept in patients with ~~the trial and the~~TB. The purpose of this ongoing study is ~~now closed. An initial presentation took place at SNMMI~~to explore using 68Ga tilmanocept as an aid in ~~June of 2018. An additional report has been submitted~~TB patient management while contributing to the ~~National Cancer Institute (“NCI”)~~better understanding of the biology of TB granulomas. CD206+ macrophages constitute one of the most abundant cell types in TB granulomas. Therefore, a molecular probe such as 68Ga-labeled tilmanocept targeting mannose receptor CD206 expressed on macrophages holds great promise not only in understanding the ~~early results~~biology of TB granulomas, but may also support future development of a tilmanocept-like drug delivery vehicle for delivering therapeutic interventions to TB granulomas. Navidea has provided tilmanocept for use in this study, and several subjects have been injected and imaged to date. Successful completion of this ~~study.~~study could support an extended claim of 68Ga-tilmanocept.

We have concluded a clinical study (ClinicalTrials.gov NCT03332940) that was originally designed to enroll 12 subjects with IV administration of Tc99m tilmanocept and an imaging comparator to identify and quantify the extent of NASH lesions in human patients. A semiquantitative evaluation of the images from the first six subjects indicated that imaging the remaining six subjects planned in the study may not sufficiently further our knowledge of Tc99m tilmanocept imaging in individuals with NASH to justify continuing the study using the current protocol. The study is now complete. Ongoing quantitative analyses of the images from the first six subjects will determine if future studies in subjects with NASH are likely to be productive. Initial results were presented at the NASH Summit in Boston in April 2018, and the results are available on Navidea’s website.

In November 2017, the Company commenced the qualification of the biomarker CD206 with the FDA Biomarker Section of The Center for Drug Evaluation and Research (“CDER”). As per FDA protocol, Navidea submitted a draft letter of intent (“LOI”) to CDER prior to the November 2017 meeting. According to the CDER directive, “the Biomarker Qualification Program was established to support the CDER’s work with external stakeholders to develop biomarkers that aid in the drug development process. Through the FDA’s Biomarker Qualification Program, an entity may request regulatory qualification of a biomarker for a particular context of use (“COU”) in drug development.” Following the meeting with the FDA, and because of Navidea’s data sets and the general external publication database, Navidea, in conjunction with FDA, is now reviewing the LOI with the FDA’s recommended consultants. Navidea has revised the LOI draft strategy in order to expedite the application process. In March 2018, Navidea had a follow-up meeting with the FDA’s assigned strategist, during which the potential to further narrow the LOI elements was reviewed. Navidea is continuing the process of finalizing the COU LOI and providing the background data sets for qualification review with the FDA/CDER. Additional meetings have taken place and the pursuit of this qualification is ~~progressing well.~~

In December 2014, the Company formed a new business unit to further explore therapeutic applications for the Manocept platform. In January 2015, Navidea incorporated the business unit as MT, a majority-owned subsidiary of Navidea. MT has developed processes for producing the first two therapeutic Manocept immuno-constructs, MT-1002, designed to specifically target and kill activated CD206+ macrophages by delivering doxorubicin, and MT-2002, designed to inhibit the inflammatory activity of activated CD206+ macrophages by delivering a potent anti-inflammatory agent. MT has contracted with independent facilities to produce sufficient quantities of the MT-1002 and MT-2002 agents along with the concomitant analytical standards, to provide material for planned preclinical animal studies and future clinical trials.

MT has been set up to pursue the therapeutic drug delivery model. This model enables the Company to leverage its technology over many potential disease applications and with multiple partners simultaneously without significant capital outlays. To date, the Company has developed two lead families of therapeutic products. The MT-1000 class is designed to deplete activated macrophages via apoptosis. The MT-2000 class is designed to modulate activated macrophages from a classically activated phenotype to the alternatively activated phenotype. Both families have been tested in a number of disease models in rodents.

We have already reported on the peripheral infectious disease aspects of KS, including HIV and HHV8 (CROI, Boston 2016, and KS HHV8 Summit Miami 2015). As noted, we continue this work funded by the NIH/NIAID and NCI. The Company has ~~completed preclinical studies employing both MT 1000-class~~been developing Manocept platform drug delivery constructs that carry various payloads including doxorubicin and ~~2000-class therapeutic conjugates of Manocept. The positive results from these studies are~~dexamethasone. Chemical synthesis techniques have advanced considerably, resulting in more robust and reproducible synthesis protocols that provide products with chemical attributes indicative of ~~Manocept’s specific targeting supported by~~enhanced in vivo activity. The most advanced drug delivery construct carries a doxorubicin payload and is now in its ~~strong binding affinity~~third generation of chemical synthesis protocol design. This third-generation doxorubicin carrying construct has been extensively evaluated in human macrophage cell culture assays and in three experiments using syngeneic mouse cancer models. These experiments show that at treatment doses below what is required to ~~CD206 receptors. This high degree~~kill macrophages, the doxorubicin-carrying constructs dramatically alters the immunological behavior of ~~specificity is a foundation~~macrophages, making them more proinflammatory. In one of the ~~potential for~~syngeneic mouse tumor experiments, the MAN-DOX construct significantly synergized the activity of another anticancer therapy producing anti-tumor activity that was greater than either treatment alone. Results from this ~~technology~~study were presented at the New York Academy of Sciences Frontiers in Cancer Immunotherapy 2021 conference on May 14, 2021. Near-term experiments with the Manocept doxorubicin construct include further studies in macrophage cell culture, additional syngeneic mouse tumor models, and a toxicity study in rats. Work involving a second generation Manocept dexamethasone-carrying construct and efforts developing Manocept constructs with different payloads is ongoing. Three new Manocept constructs carrying payloads other than doxorubicin or dexamethasone have progressed to ~~be useful~~evaluations in ~~treating diseases linked to the over-activation of macrophages. This includes various cancers as well as autoimmune, infectious, CV, and central nervous system (“CNS”) diseases.~~macrophage cell culture assays.

The novel ~~MT-1000~~MAN-DOX class constructs are designed to specifically deliver doxorubicin, a chemotoxin, which can kill KS tumor cells and their tumor-associated macrophages, potentially altering the course of cancer. We ~~have~~ received additional funding to continue therapeutic studies in this disease with the goal of completing an investigational new drug (“IND”) submission for a Manocept construct ~~(MT-1000~~(MAN-DOX class of compounds) consisting of tilmanocept linked to doxorubicin for the treatment of KS. ~~The first part of the~~Efforts supported by this grant ~~now complete, supported analyses including~~ ~~in vitro~~ and cell culture studies, to be followed by Parts 2 and 3 FDA-required preclinical animal testing studies. The information from these studies will be combined with other information in an IND application that will be submitted to the FDA requesting permission to begin testing the compound in selected KS subjects (supported by NIH/(NIH/NCI 1 R44 CA206788-01).

~~NAFLD is a spectrum~~ are now complete. The results greatly advanced our knowhow for robustly and reproducibly synthesizing MAN-DOX and related constructs carrying other payloads. The grant-supported efforts were presented at the New York Academy of ~~liver disorders and is defined by the presence of steatosis~~Sciences Frontiers in more than 5% of hepatocytes with little or no alcohol consumption. NASH is the most extreme form of NAFLD. A major characteristic of NASH involves cells undergoing lipotoxicity, releasing endogenous signals prompting the accumulation of various macrophages to assess the damage. Studies have shown that levels of endogenous molecular inflammatory signals positively correlate with inflammation, hepatocyte ballooning, and other NAFLD symptoms. We have developed a molecular delivery technology capable of targeting disease-causing macrophages by selectively binding to the CD206 receptor. Selective binding and efficient delivery of this agent diminishes the potential of interfering more broadly with the normal function of the immune system.Cancer Immunotherapy 2021.

~~We have completed five~~ ~~in vivo~~ studies employing our MT-1002 and MT-2002 Manocept conjugates in a mouse model of NAFLD/NASH and liver fibrosis. The NALFD scores, which correlate to the agents’ effectiveness, were significantly reduced, with all the activity related to inflammation and “ballooning” scores. Fibrosis decreased significantly when compared to the control in the later dosing arm of the study. Liver weights did not differ during any phase of the study between control and agent-treated groups, nor was there any evidence of damage to the roughly 30% of the liver made up of un-activated macrophages called Kupffer cells. MT-1002 and MT-2002 both significantly reduced key disease assessment parameters in the ~~in vivo~~ ~~STAM~~^TM ~~NASH model. We believe these agents present themselves as potential clinically effective candidates for further evaluation. We continue to use this model to further assess the activity of our agents.~~

~~We have completed an expanded series of predictive~~ ~~in vitro~~ screening tests of the MT-1002 and MT-2002 therapeutic conjugates against the Zika and Dengue viruses, which included infectivity and viral replication inhibition effectiveness as well as dose finding studies and mechanisms of action, the latter based on conjugate structures. We have also completed a series of predictive ~~in vivo~~ screening tests of the MT-1002 and MT-2002 therapeutic conjugates against Leishmaniosis, which included host cell targeting and killing effectiveness as well as dose finding studies and mechanisms of action. A portion of the results from the ~~in vivo~~ ~~Leishmaniosis study, completed in conjunction with the National Institute of Allergy and Infectious Diseases/NIH, was recently published in the~~ ~~Journal of Experimental Medicine (~~~~published in the circulated version~~ ~~Journal of Experimental Medicine~~ ~~2018 Jan 2;215(1):357-375).The results from all evaluations were positive and have provided a basis for moving forward with additional~~ ~~in vivo~~ ~~testing of the selected conjugates. We have selected collaborators for these~~ ~~in vivo~~ ~~studies, which we expect will take place over the next four to six months. We will provide updates as information becomes available on future testing.~~

The Company continues to evaluate emerging data in other disease states to define areas of focus, development pathways and partnering options to capitalize on the Manocept platform, including ongoing studies in KS, RA and infectious diseases. The immuno-inflammatory process is remarkably complex and tightly regulated with indicators that initiate, maintain and shut down the process. Macrophages are immune cells that play a critical role in the initiation, maintenance, and resolution of inflammation. They are activated and deactivated in the inflammatory process. Because macrophages may promote dysregulation that accelerates or enhances disease progression, diagnostic and therapeutic interventions that target macrophages may open new avenues for controlling inflammatory diseases. There can be no assurance that further evaluation or development will be successful, that any Manocept platform product candidate will ultimately achieve regulatory approval, or if approved, the extent to which it will achieve market acceptance.

NAV4694 is a fluorine-18 (“F-18”) labeled PET imaging agent being developed as an aid in the imaging and evaluation of patients with signs or symptoms of Alzheimer’s disease (“AD”) and mild cognitive impairment (“MCI”). NAV4694 binds to beta-amyloid deposits in the brain that can then be imaged in PET scans. Amyloid plaque pathology is a required feature of AD and the presence of amyloid pathology is a supportive feature for diagnosis of probable AD. Patients who are negative for amyloid pathology do not have AD. NAV4694 has been studied in rigorous pre-clinical studies and clinical trials in humans. Clinical studies through Phase 3 have included subjects with MCI, suspected AD patients, and healthy volunteers. Results suggest that NAV4694 has the potential ability to image patients quickly and safely with high sensitivity and specificity.

In May 2014, the Board of Directors made the decision to refocus the Company's resources to better align the funding of our pipeline programs with the expected growth in Tc99m tilmanocept revenue. This realignment primarily involved reducing our near-term support for our neurological product candidates, including NAV4694, as we sought a development partner or partners for these programs. In April 2018, the Company executed an agreement to provide Meilleur, a wholly-owned subsidiary of Cerveau Technologies, Inc. (“Cerveau”), worldwide rights to conduct research using NAV4694, as well as an exclusive license for the development and commercialization of NAV4694 in Australia, Canada, China, and Singapore. Meilleur also has an option to commercialize worldwide.

Cancer is the second leading cause of death in the United States. The American Cancer Society (“ACS”) estimates that cancer will cause over 600,000 deaths in ~~2019~~2022 in the United States alone. Additionally, the ACS estimates that ~~approximately 1.7~~over 1.9 million new cancer cases will be diagnosed in the United States during ~~2019.~~2022. The ~~Agency for Healthcare Research and Quality has estimated~~National Cancer Institute estimates that ~~the~~ direct medical costs for cancer in the United States for 2015 were ~~$80.2 billion.~~$183 billion, and are projected to increase to $246 billion by 2030. Cancer is also the second leading cause of death in Europe. The World Health Organization reports more than 3.7 million new cases and 1.9 million deaths in Europe each year.

Tc99m tilmanocept is approved by the FDA for use in solid tumor cancers where lymphatic mapping is a component of surgical management and for guiding sentinel lymph node biopsy in patients with clinically node negative breast cancer, head and neck cancer, melanoma or squamous cell carcinoma of the oral cavity. Tc99m tilmanocept has also received European approval in imaging and intraoperative detection of sentinel lymph nodes in patients with melanoma, breast cancer or localized squamous cell carcinoma of the oral cavity. If the potential of Tc99m tilmanocept as a radioactive tracing agent is ultimately realized, it may address not only the breast and melanoma markets on a procedural basis, but also assist in the clinical evaluation and staging of solid tumor cancers and expanding lymph node mapping to other solid tumor cancers such as prostate, gastric, colon, gynecologic, and non-small cell lung.

Impairment of the macrophage-driven disease mechanism is an area of increasing focus in medicine. There are many recognized disorders having macrophage involvement, including RA, atherosclerosis/vulnerable plaque, Crohn’s disease, TB, systemic lupus erythematosus, KS, and others that span clinical areas in oncology, autoimmunity, infectious diseases, cardiology, and inflammation. The number of people affected by all the inflammatory diseases combined is estimated at more than 40 million in the United States, making these macrophage-mediated diseases an area of significant clinical importance. The Arthritis Foundation estimates that RA alone affects over 1.5 million people in the United States and as much as 1% of the worldwide population. Based on 2005 U.S. Medicare/Medicaid data, total annual societal costs of RA are estimated to be $39.2 billion. Data from studies using agents from the Manocept platform in RA, KS and TB were published in a special supplement, ~~Nature Outlook: Medical~~~~Imaging~~~~, in~~ ~~Nature’s~~ ~~October 31, 2013 issue. The supplement included a White Paper by Navidea entitled “~~~~Innovations in receptor-targeted precision imaging at Navidea: Diagnosis up close and personal,~~~~” focused on the Manocept platform.~~

The Alzheimer’s Association (“AA”) estimates that more than 5.7 million Americans had AD in 2018. On a global basis, Alzheimer’s Disease International estimated in 2015 that there were 46.8 million people living with dementia, and this number is believed to be close to 50 million people in 2017. This number is expected to almost double every 20 years, reaching 75 million in 2030 and over 130 million in 2050. AD is the sixth-leading cause of death in the U.S. and the only cause of death among the top 10 in the U.S. that cannot be prevented, cured or even slowed. Based on U.S. mortality data from 2000 to 2015, deaths from AD have risen 123 percent while deaths attributed to the number one cause of death, heart disease, decreased 11 percent during the same period. AA estimates that total costs for AD care was approximately $259.0 billion in 2017. AA also estimates that there are over 16 million AD and dementia caregivers providing 18.4 billion hours of unpaid care valued at over $232.0 billion.

InFollowing Navidea’s March 2017 ~~Navidea completed the Asset Sale~~sale to Cardinal Health 414, ~~as discussed previously under “Development~~LLC (“Cardinal Health 414”) of ~~the Business.” Pursuant to the Purchase Agreement, we sold~~ all of ~~our~~its assets ~~used, held for use, or intended to be~~ used in operating its business of developing, manufacturing and commercializing the ~~Business, including~~Company’s radioactive diagnostic agent marketed under the ~~Product,~~Lymphoseek® trademark in Canada, Mexico and the ~~Territory. Upon closing of the Asset Sale,~~United States, the Supply and Distribution Agreement between Cardinal Health 414 and ~~the Company~~Navidea was terminated and Cardinal Health 414 ~~has~~ assumed responsibility for marketing Lymphoseek in ~~the Territory.~~those territories.

Unlike in the United States, where institutions typically rely on radiopharmaceutical products that are compounded and delivered by specialized radiopharmacy distributors such as Cardinal Health 414, institutions in Europe predominantly purchase non-radiolabeled material and compound the radioactive product on-site. With respect to Tc99m tilmanocept commercialization in Europe, we ~~have chosen~~initially chose a specialty pharmaceutical strategy that ~~should~~we believed would be supportive of premium product positioning and reinforce Tc99m tilmanocept's clinical value proposition, as opposed to a commodity or a generics positioning approach. InOn March 5, 2015, weNavidea entered into an ~~exclusive sublicense agreement~~Exclusive License Agreement (as amended to date, the “License Agreement”) for the commercialization and distribution of a ~~50 microgram~~50-microgram kit for radiopharmaceutical preparation (tilmanocept) in the European Union (“EU”) with SpePharm AG ~~(an~~(“SpePharm,” an affiliate of Norgine BV), a European specialist pharmaceutical company with an extensive pan-European presence. Under the ~~terms of~~License Agreement, SpePharm had the exclusive ~~license agreement,~~right to develop, manufacture and commercialize the Company’s products approved for radiolabeling with Tc99m and containing Lymphoseek (collectively, the “Products”) in several jurisdictions abroad, including the United Kingdom, France, Germany, Australia and New Zealand (collectively, the “Licensed Territory”). In exchange for such rights, the Company was entitled to certain royalty payments. In accordance with the License Agreement, Navidea transferred responsibility for regulatory maintenance of the Tc99m tilmanocept Marketing Authorization to SpePharm. SpePharm ~~in January 2017. SpePharm is~~was also responsible for production, distribution, pricing, reimbursement, sales, marketing, medical affairs, and regulatory activities.

On May 11, 2020 (the “Termination Date”), the Company entered into a Termination Agreement (the “Termination Agreement”) with SpePharm AG (“SpePharm”) and Norgine BV (“Norgine”) which terminated that certain Exclusive License Agreement dated March 5, 2015 (as amended to date, the “License Agreement”). Under the License Agreement, SpePharm had the exclusive right to develop, manufacture and commercialize the Company’s products approved for radiolabeling with Tc99m and containing Lymphoseek® (collectively, the “Products”) in several jurisdictions abroad, including the United Kingdom, France, Germany, Australia and New Zealand (collectively, the “Licensed Territory”). In ~~connection with entering into~~exchange for such rights, the ~~agreement, Navidea received an upfront payment of $2.0 million, and is~~Company was entitled to ~~milestones totaling up~~certain royalty payments.

Pursuant to ~~an additional $5.0 million~~the Termination Agreement, the parties agreed that neither owed the other any payments due under the License Agreement as of the Termination Date and ~~royalties on European net sales. The initial territory covered~~that, among other things, SpePharm no longer has any right in, nor claim to, any intellectual property owned by the ~~agreement includes all 28 member states~~Company or its affiliates anywhere in the world. SpePharm also agreed to perform certain wind-down activities (the “Wind-Down Activities”) during the six-month period following the Termination Date (the “Transition Period”), which Transition Period was extended by ninety days. The Wind-Down Activities included, without limitation, SpePharm transferring to the Company or its designee(s) the regulatory approvals controlled by SpePharm or its affiliates for the purpose of marketing, distributing and selling the Products in the Licensed Territory. SpePharm also transferred to the Company certain tenders and other customer and sales contracts related to the Products. Subject to the terms of the Termination Agreement, Norgine, an affiliate of SpePharm, agreed to guarantee SpePharm’s performance of its obligations under the Termination Agreement. Although the Transition Period has elapsed, SpePharm continued to fulfill customer orders until the Company obtained the regulatory license required to distribute the product in Europe, which license was received during the fourth quarter of 2021.

On June 9, 2020, Navidea established a new European ~~Economic Community~~entity, Navidea Biopharmaceuticals Europe Limited (“Navidea Europe”), to address international development and commercialization needs for our technologies, including Tc99m tilmanocept. SpePharm has transferred the Tc99m tilmanocept Marketing Authorization to Navidea Europe, along with the ~~option to expand into additional geographical areas. During the second quarter~~responsibility for production and commercialization of ~~2017, SpePharm launched~~ Tc99m tilmanocept in ~~select EU markets, providing a number~~the Licensed Territory. Navidea Europe has established relationships and executed agreements with third-party providers in order to fulfill such responsibilities. Navidea owns 100% of ~~early adopters with sample doses to provide exposure to~~ the ~~product. EU sales commenced during the third quarter~~outstanding shares of ~~2017.~~Navidea Europe.

In August 2014, Navidea entered into an exclusive agreement with Beijing Sinotau Medical Research Co., Ltd. (“Sinotau”), a pharmaceutical organization with a broad China focus in oncology and other therapeutic areas, who will develop and commercialize Tc99m tilmanocept in China. In exchange, Navidea will earn revenue based on unit sales to Sinotau, royalties based on Sinotau’s sales of Tc99m tilmanocept and milestone payments from Sinotau, including a $300,000 non-refundable upfront payment. As part of the agreement, Sinotau is responsible for costs and conduct of clinical studies and regulatory applications to obtain Tc99m tilmanocept approval by the China Food and Drug Administration (“CFDA”). Upon approval, Sinotau will be responsible for all Tc99m tilmanocept sales, marketing, market access and medical affairs activities in China and excluding Hong Kong, Macau and Taiwan. Navidea and Sinotau will jointly support certain pre-market planning activities with a joint commitment on clinical and market development programs pending CFDA approval.

In June 2017, Navidea entered into an exclusive license and distribution agreement with Sayre Therapeutics (“Sayre”) for the development and commercialization of Tc99m tilmanocept in India. Sayre specializes in innovative treatments and medical devices commercialization in South Asia. Under the terms of the agreement, Navidea received a $100,000 upfront payment and is eligible to receive milestone payments and double-digit royalties associated with the sale of Tc99m tilmanocept in India. Tc99m tilmanocept has not yet received marketing approval in India.

Tc99m tilmanocept is in various stages of approval in other global markets and sales to this point in these markets, to the extent there were any, have not been material. However, we believe that with international partnerships to complement our positions in the EU, China and India, we will help establish Tc99m tilmanocept as a global leader in lymphatic mapping, as we are not aware of any other company that has a global geographic range. However, it is possible that Tc99m tilmanocept will never achieve regulatory approval in any market outside the United States or EU, or if approved, that it may not achieve market acceptance in any market. We may also experience difficulty in securing collaborative partners for other global markets or radiopharmaceutical products, or successfully negotiating acceptable terms for such arrangements. See Item 1A - “Risk Factors.”

We currently use and expect to continue to be dependent upon contract manufacturers to manufacture each of our product candidates. We ~~have established~~maintain a quality control and quality assurance program, including a set of standard operating procedures and specifications, with the goal that our products and product candidates are manufactured in accordance with current good manufacturing practices (“cGMP”) and other applicable domestic and international regulations. We ~~may need to invest~~are investing in additional manufacturing and supply chain resources, and ~~may seek to enter~~have entered into ~~additional collaborative arrangements~~development contracts with ~~other parties that have~~the established manufacturing ~~capabilities.~~companies Corden Pharma Switzerland, LLC for active pharmaceutical ingredient production and ROTOP Pharmaka GmbH for drug product manufacturing. It is likely that we will continue to rely on third-party manufacturers for our development and commercial products on a contract basis.

In November 2009, we completed a Manufacture and Supply Agreement with Reliable Biopharmaceutical Corporation (“Reliable”) for the manufacture of the bulk drug substance with an initial term of 10 years. In September 2013, we entered into a Manufacturing Services Agreement with OSO BioPharmaceuticals Manufacturing, LLC (“OsoBio”) for contract pharmaceutical development, manufacturing, packaging and analytical services for Tc99m tilmanocept. Also in September 2013, we completed a Service and Supply Master Agreement with Gipharma S.r.l. (“Gipharma”) for process development, manufacturing and packaging of 50-microgram vials for sale in the EU. Upon closing of the Asset Sale to Cardinal Health 414, our contracts with Reliable and OsoBio were transferred to Cardinal Health 414. Similarly, following the transfer of the Tc99m tilmanocept Marketing Authorization to SpePharm, our contract with Gipharma was transferred to SpePharm. We may not be successful in completing ~~future~~long-term agreements for the supply of Tc99m tilmanocept on terms acceptable to the Company, or at all. See Item 1A - “Risk Factors.”

Competition in the pharmaceutical and biotechnology industries is intense. We face competition from a variety of companies focused on developing inflammatory, oncology and ~~neurology~~CV disease diagnostic ~~drugs.~~imaging agents and other diagnostic modalities. We compete with large pharmaceutical and other specialized biotechnology companies. We also face competition from universities and other non-profit research organizations. ~~Many~~any emerging medical product companies have corporate partnership arrangements with large, established companies to support the research, development, and commercialization of products that may be competitive with our products. In addition, a number of large established companies are developing proprietary technologies or have enhanced their capabilities by entering into arrangements with or acquiring companies with technologies applicable to the detection or treatment of cancer and other diseases targeted by our product candidates. Smaller companies may also prove to be significant competitors, particularly through collaborative arrangements with large pharmaceutical and established biotechnology companies. Many of these competitors have products that have been approved or are in development and operate large, well-funded research and development (“R&D”) programs. Many of our existing or potential competitors have substantially greater financial, ~~research and development,~~R&D, regulatory, marketing, and production resources than we have. Other companies may develop and introduce products and processes competitive with or superior to ours.

We expect to encounter significant competition for our pharmaceutical products. Companies that complete clinical trials, obtain required regulatory approvals and commence commercial sales of their products before us may achieve a significant competitive advantage if their products work through a similar mechanism as our products and if the approved indications are similar. A number of biotechnology and pharmaceutical companies are developing new products for the diagnosis and/or treatment of the same diseases being targeted by us. In some instances, such products have already entered late-stage clinical trials or received FDA approval and may be marketed for some period prior to the approval of our products.

We believe that our ability to compete successfully will be based on our ability to create and maintain scientifically advanced “best-in-class” technology, develop proprietary products, attract and retain scientific personnel, obtain patent or other protection for our products, obtain required regulatory approvals and manufacture and successfully market our products, either alone or through third parties. We expect that competition among products cleared for marketing will be based on, among other things, product efficacy, safety, reliability, availability, price, and patent position. See Item 1A - “Risk Factors.”

Tc99m Tilmanocept Competition –T~~ilmanocept~~ ~~Competition~~ – Currently Approved Indications

~~Surgeons~~Some surgeons who practice the lymphatic mapping procedure for which Tc99m tilmanocept is intended currently use other radiopharmaceuticals such as a sulfur colloid or other colloidal compounds. In addition, some surgeons still use vital blue dyes to assist in the visual identification of the draining lymphatic tissue around a primary tumor. In the EU and certain Pacific Rim markets, there are colloidal-based compounds with various levels of approved labeling for use in lymphatic mapping, although a number of countries still employ products used “off-label.”

Currently, no single test is available to diagnose and monitor RA. Rather, a rheumatologist will make a diagnosis based on several procedures that may include a physical exam, blood tests, and/or imaging tests, among others. The Arthritis Foundation states that the goals of RA treatment are to relieve symptoms, stop inflammation, prevent joint and organ damage, improve physical function and well-being, and reduce long-term complications. Medications for the treatment of RA currently fall into two categories: drugs that ease symptoms, such as nonsteroidal anti-inflammatory drugs, and drugs that slow disease activity. Drugs that slow disease activity include corticosteroids, biologic disease-modifying antirheumatic drugs ~~biologics,~~(“bDMARDs”) and Janus kinase inhibitors. Many of these drugs are produced and sold by large pharmaceutical companies, including AbbVie, Amgen, Bristol Meyers Squibb, Johnson & Johnson, Merck, Pfizer and Roche, among others.

One of Navidea’s primary goals for its RA imaging product development program is to develop an imaging-based test that can predict patient-specific therapeutic responses to bDMARDs, especially anti-TNFα antibody therapy, which is the most commonly prescribed type of therapy for RA within this drug class. While no tests predicting therapeutic responses to bDMARDs have been approved by the FDA, Navidea is aware of other groups that are working to develop such tests, primarily blood-based biomarker assays. One or more of these tests could be approved by the FDA in the future, making it possible for them to compete directly with Navidea’s imaging-based RA test. Even without FDA approval, these tests could reduce the Company’s share of this market in the future.

The patent position of biotechnology companies, including Navidea, generally is highly uncertain and may involve complex legal and factual questions. Potential competitors may have filed applications, or may have been issued patents, or may obtain additional patents and proprietary rights relating to products or processes in the same area of technology as that used by the Company. The scope and validity of these patents and applications, the extent to which we may be required to obtain licenses thereunder or under other proprietary rights, and the cost and availability of licenses are uncertain. Our patent applications or those licensed to us may not result in additional patents being issued, and our patents or those licensed to us may not afford protection against competitors with similar technology; these patents may be designed around by others or others may obtain patents that we would need to license or design around.

We also rely upon unpatented trade secrets. Others may independently develop substantially equivalent proprietary information and techniques, or otherwise gain access to our trade secrets, or disclose such technology, or we may not be able to meaningfully protect our rights to our unpatented trade secrets.

We require our employees, consultants, advisers, and suppliers to execute a confidentiality agreement upon the commencement of an employment, consulting or manufacturing relationship with us. The agreement provides that all confidential information developed by or made known to the individual during the course of the relationship will be kept confidential and not disclosed to third parties except in specified circumstances. In the case of employees, the agreements provide that all inventions conceived by the individual will be the exclusive property of our company. However, these agreements may not provide meaningful protection for our trade secrets in the event of an unauthorized use or disclosure of such information. We also employ a variety of security measures to preserve the confidentiality of our trade secrets and to limit access by unauthorized persons. However, these measures may not be adequate to protect our trade secrets from unauthorized access or disclosure. See Item 1A - “Risk Factors.”

Tilmanocept is under license from ~~UCSD~~the University of California, San Diego (“UCSD”) to Navidea for the exclusive world-wide rights in all diagnostic and therapeutic uses of tilmanocept, except for the ~~diagnostic~~ use of Tc99m tilmanocept in lymphatic mapping in Canada, Mexico and the United States, which rights have been licensed directly to Cardinal Health 414 by ~~UCSD in connection with the Asset Sale.~~UCSD. Navidea maintains license rights to Tc99m tilmanocept in the rest of the world, as well as a license to the intellectual property underlying the Manocept platform.

Tc99m tilmanocept and related compositions, including the Manocept backbone composition and methods of use, are the subject of multiple patent families ~~totaling 44~~including issued patents and patent applications in the United States and certain major foreign markets.

The first composition of matter patent covering tilmanocept was issued to UCSD in the United States in June 2002 and ~~will expire~~would have expired in May ~~2020, however~~2020. However, Navidea ~~has applied for~~was granted a five-year patent term extension under the Hatch Waxman Act ~~that would extend the term by five years~~ due to time lost in regulatory review. The claims of the composition of matter patent covering tilmanocept ~~have been allowed in the EU and~~ issued in the majority of major-market EUEuropean countries in ~~2004. These patents will expire~~2004 and would have expired in ~~2020, but a request for~~2020. However, the Company has obtained supplemental protection certificates, ~~are in process to further extend the life of these patents, and some have been granted,~~ extending the patent ~~term~~terms to 2025. The composition of matter patent ~~has also been~~ issued in Japan ~~which will expire~~expired in 2020.

Patent applications have been filed by Navidea in the U.S. and certain major foreign markets related to manufacturing processes for tilmanocept, the first of which was issued in the U.S. in 2013. These patents and/or applications will expire between 2029 and 2034. Further patent applications have been filed by Navidea alone or with The Ohio State Innovation Foundation related to CD206 expressing cell-related disorders and diseases. These patents and/or applications ~~would be~~are expected to expire between 2034 and ~~2035. We have filed further patent applications related to 2-heteroaryl substituted benzofurans. These patents and/or applications will expire between 2036 and 2038.~~2041.

The research, development, testing, manufacture, labeling, promotion, advertising, distribution and marketing, among other things, of our products are extensively regulated by governmental authorities in the United States and other countries. In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, Public Health Service Act, and their implementing regulations. Failure to comply with applicable U.S. requirements may subject us to administrative or judicial sanctions, such as FDA refusal to approve pending new drug applications or supplemental applications, warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions and/or criminal prosecution. We also may be subject to regulation under the Occupational Safety and Health Act, the Atomic Energy Act, the Toxic Substances Control Act, the Export Control Act and other present and future laws of general application as well as those specifically related to radiopharmaceuticals.

Most aspects of our business are subject to some degree of government regulation in the countries in which we conduct our operations. As a developer, manufacturer and marketer of medical products, we are subject to extensive regulation by, among other governmental entities, the FDA and the corresponding state, local and foreign regulatory bodies in jurisdictions in which our products are intended to be sold. These regulations govern the introduction of new products, the observance of certain standards with respect to the manufacture, quality, safety, efficacy and labeling of such products, the maintenance of certain records, the tracking of such products, performance surveillance and other matters.

Failure to comply with applicable federal, state, local or foreign laws or regulations could subject us to enforcement action, including product seizures, recalls, withdrawal of marketing clearances, and civil and criminal penalties, any one or more of which could have a material adverse effect on our business. We believe that we are in substantial compliance with such governmental regulations. However, federal, state, local and foreign laws and regulations regarding the manufacture and sale of radiopharmaceuticals are subject to future changes. Such changes may have a material adverse effect on our company.

For some products, and in some countries, government regulation is significant and, in general, there is a trend toward more stringent regulation. In recent years, the FDA and certain foreign regulatory bodies have pursued a more rigorous enforcement program to ensure that regulated businesses like ours comply with applicable laws and regulations. We devote significant time, effort and expense addressing the extensive governmental regulatory requirements applicable to our business. To date, we have not received a noncompliance notification or warning letter from the FDA or any other regulatory bodies of alleged deficiencies in our compliance with the relevant requirements, nor have we recalled or issued safety alerts on any of our products. However, a warning letter, recall or safety alert, if it occurred, could have a material adverse effect on our company. See Item 1A - “Risk Factors.”

In the early- to mid-1990s, the review time by the FDA to clear medical products for commercial release lengthened and the number of marketing clearances decreased. In response to public and congressional concern, the FDA Modernization Act of 1997 (the “1997 Act”) was adopted with the intent of bringing better definition to the clearance process for new medical products. While the FDA review times have improved since passage of the 1997 Act, theThe FDA review processes could delay our Company's introduction of new products in the United States in the future. In addition, many foreign countries have adopted more stringent regulatory requirements that also have added to the delays and uncertainties associated with the development and release of new products, as well as the clinical and regulatory costs of supporting such releases. It is possible that delays in receipt of, or failure to receive, any necessary clearance for our new product offerings could have a material adverse effect on our business, financial condition or results of operations. See Item 1A - “Risk Factors.”

None of our drugs may be marketed in the United States until such drug has received FDA approval. The steps required before a drug may be marketed in the United States include:

Preclinical tests include laboratory evaluation of product chemistry, toxicity and formulation, as well as animal studies. The conduct of the preclinical tests and formulation of the compounds for testing must comply with federal regulations and requirements. The results of the preclinical tests, together with manufacturing information and analytical data, are submitted to the FDA as part of an IND, which must become effective before human clinical trials may begin. An IND will automatically become effective 30 days after receipt by the FDA unless, before that time, the FDA raises concerns or questions about issues such as the conduct of the trials as outlined in the IND. In such a case, the IND sponsor and the FDA must resolve any outstanding FDA concerns or questions before clinical trials can proceed. We cannot be sure that submission of an IND will result in the FDA allowing clinical trials to begin.

Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators. Clinical trials are conducted under protocols detailing the objectives of the study, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated. Each protocol must be submitted to the FDA as part of the IND.

Clinical trials typically are conducted in three sequential phases, but the phases may overlap or be combined. The study protocol and informed consent information for study subjects in clinical trials must also be approved by an institutional review board at each institution where the trials will be conducted. Study subjects must sign an informed consent form before participating in a clinical trial. Phase 1 usually involves the initial introduction of the investigational product into people to evaluate its short-term safety, dosage tolerance, metabolism, pharmacokinetics and pharmacologic actions, and, if possible, to gain an early indication of its effectiveness. Phase 2 usually involves trials in a limited subject population to (i) evaluate dosage tolerance and appropriate dosage, (ii) identify possible adverse effects and safety risks, and (iii) evaluate preliminarily the efficacy of the product candidate for specific indications. Phase 3 trials usually further evaluate clinical efficacy and further test its safety by using the product candidate in its final form in an expanded subject population. There can be no assurance that Phase 1, Phase 2 or Phase 3 testing will be completed successfully within any specified period of time, if at all. Furthermore, we or the FDA may suspend clinical trials at any time on various grounds, including a finding that the subjects or patients are being exposed to an unacceptable health risk.

The FDA and the IND sponsor may agree in writing on the design and size of clinical studies intended to form the primary basis of an effectiveness claim in an NDA application. This process is known as a Special Protocol Assessment (“SPA”). These agreements may not be changed after the clinical studies begin, except in limited circumstances. The existence of a SPA, however, does not assure approval of a product candidate.

Assuming successful completion of the required clinical testing, the results of the preclinical studies and of the clinical studies, together with other detailed information, including information on the manufacturing quality and composition of the investigational product, are submitted to the FDA in the form of an NDA requesting approval to market the product for one or more indications. The testing and approval process requires substantial time, effort and financial resources. Submission of an NDA requires payment of a substantial review user fee to the FDA. Before approving aan NDA, the FDA usually will inspect the facility or the facilities where the product is manufactured, tested and distributed and will not approve the product unless cGMP compliance is satisfactory. If the FDA evaluates the NDA and the manufacturing facilities as acceptable, the FDA may issue an approval letter or a complete response letter. A complete response letter outlines conditions that must be met in order to secure final approval of the NDA. When and if those conditions have been met to the FDA’s satisfaction, the FDA will issue an approval letter. The approval letter authorizes commercial marketing of the drug for specific indications. As a condition of approval, the FDA may require post-marketing testing and surveillance to monitor the product’s safety or efficacy, or impose other post-approval commitment conditions.

The FDA has various programs, including fast track, priority review and accelerated approval, which are intended to expedite or simplify the process of reviewing drugs and/or provide for approval on the basis of surrogate endpoints. Generally, drugs that may be eligible for one or more of these programs are those for serious or life threatening conditions, those with the potential to address unmet medical needs and those that provide meaningful benefit over existing treatments. Our drug candidates may not qualify for any of these programs, or, if a drug candidate does qualify, the review time may not be reduced or the product may not be approved.

After approval, certain changes to the approved product, such as adding new indications, making certain manufacturing changes or making certain additional labeling claims, are subject to further FDA review and approval. Obtaining approval for a new indication generally requires that additional clinical studies be conducted.

Holders of an approved NDA are required to: (i) conduct pharmacovigilance and report certain adverse reactions to the FDA, (ii) comply with certain requirements concerning advertising and promotional labeling for their products, and (iii) continue to have quality control and manufacturing procedures conform to cGMP. The FDA periodically inspects the sponsor’s records related to safety reporting and/or manufacturing and distribution facilities; this latter effort includes assessment of compliance with cGMP. Accordingly, manufacturers must continue to expend time, money and effort in the area of production, quality control and distribution to maintain cGMP compliance. We use and will continue to use third-party manufacturers to produce our products in clinical and commercial quantities, and future FDA inspections may identify compliance issues at our facilities or at the facilities of our contract manufacturers that may disrupt production or distribution, or require substantial resources to correct.

Marketing of prescription drugs is also subject to significant regulation through federal and state agencies tasked with consumer protection and prevention of medical fraud, waste and abuse. We must comply with restrictions on off-label use promotion, anti-kickback, ongoing clinical trial registration, and limitations on gifts and payments to physicians.

Before our products can be marketed outside of the United States, they are subject to regulatory approval similar to that required in the United States, although the requirements governing the conduct of clinical trials, including additional clinical trials that may be required, product licensing, pricing and reimbursement vary widely from country to country. No action can be taken to market any product in a country until an appropriate application has been approved by the regulatory authorities in that country. The current approval process varies from country to country, and the time spent in gaining approval varies from that required for FDA approval. In certain countries, the sales price of a product must also be approved. The pricing review period often begins after market approval is granted. Even if a product is approved by a regulatory authority, satisfactory prices may not be approved for such product.

In Europe, marketing authorizations may be submitted at a centralized, a decentralized or national level. The centralized procedure is mandatory for the approval of biotechnology products and provides for the grant of a single marketing authorization that is valid in all EU member states. A mutual recognition procedure is available at the request of the applicant for all medicinal products that are not subject to the centralized procedure.

The European Commission granted marketing authorization for Tc99m tilmanocept in the EU in November 2014, and a reduced-mass vial developed for the EU market was approved in September 2016.

While we are unable to predict the extent to which our business may be affected by future regulatory developments, we believe that our substantial experience dealing with governmental regulatory requirements and restrictions on our operations throughout the world, and our development of new and improved products, should enable us to compete effectively within this environment.

Our radiolabeled targeting agents and biologic products, if developed, would require a regulatory license to market from the FDA and from comparable agencies in foreign countries. The process of obtaining regulatory licenses and approvals is costly and time consuming, and we have encountered significant impediments and delays related to our previously proposed biologic products.

The process of completing pre-clinical and clinical testing, manufacturing validation and submission of a marketing application to the appropriate regulatory bodies usually takes a number of years and requires the expenditure of substantial resources, and any approval may not granted on a timely basis, if at all. Additionally, the length of time it takes for the various regulatory bodies to evaluate an application for marketing approval varies considerably, as does the amount of preclinical and clinical data required to demonstrate the safety and efficacy of a specific product. The regulatory bodies may require additional clinical studies that may take several years to perform. The length of the review period may vary widely depending upon the nature and indications of the proposed product and whether the regulatory body has any further questions or requests any additional data. Also, the regulatory bodies require post-marketing reporting and surveillance programs (pharmacovigilance) to monitor the side effects of the products. Our potential drug or biologic products may not be approved by the regulatory bodies or may not be approved on a timely or accelerated basis, or any approvals received may subsequently be revoked or modified.

The Nuclear Regulatory Commission (“NRC”) oversees medical uses of nuclear material through licensing, inspection, and enforcement programs. The NRC issues medical use licenses to medical facilities and authorized physician users, develops guidance and regulations for use by licensees, and maintains a committee of medical experts to obtain advice about the use of byproduct materials in medicine. The NRC (or the responsible Agreement State) also regulates the manufacture and distribution of these products. The FDA oversees the good practices in the manufacturing of radiopharmaceuticals, medical devices, and radiation-producing x-ray machines and accelerators. The states regulate the practices of medicine and pharmacy and administer programs associated with radiation-producing x-ray machines and accelerators. We may not be able to obtain all necessary licenses and permits and we may not be able to comply with all applicable laws. The failure to obtain such licenses and permits or to comply with applicable laws would have a materially adverse effect on our business, financial condition, and results of operations.

Our executive offices are located at 4995 Bradenton Avenue, Suite 240, Dublin, OH 43017. Our telephone number is (614) 793-7500. “Navidea” and the Navidea logo are trademarks of Navidea Biopharmaceuticals, Inc. or its subsidiaries in the United States and/or other countries. Other trademarks or service marks appearing in this report may be trademarks or service marks of other owners.

The address for our website is ~~http://~~www.navidea.com. We make available free of charge on our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), and amendments to such filings, as soon as reasonably practicable after each is electronically filed with, or furnished to, the Securities Exchange Commission (“SEC”). We do not charge for access to and viewing of these reports. Information in the investor section and on our website is not part of this Annual Report on Form 10-K or any of our other securities filings unless specifically incorporated herein by reference.

~~In addition, the public~~You may ~~read~~also review our electronically filed reports and ~~copy any materials~~other information that we file with the SEC ~~at the SEC’s Public Reference Room at 100 F Street, NE, Washington, D.C. 20549. The public may obtain information~~ on ~~the operation of the Public Reference Room by calling the SEC at 1-800-SEC-0330. Also, our filings with the SEC may be accessed through~~ the SEC’s website at ~~www.sec.gov.~~www.sec.gov. All statements made in any of our securities filings, including all forward-looking statements or information, are made as of the date of the document in which the statement is included, and we do not assume or undertake any obligation to update any of those statements or documents unless we are required to do so by law.

Our consolidated financial statements and the related notes, including revenues, income (loss), total assets and other financial measures are set forth at pages F-1 through ~~F-36~~F-32 of this Annual Report on Form 10-K.

As of March ~~1, 2019,~~18, 2022, we had 1411 full-time and 54 part-time employees. None of our employees are represented by a collective bargaining agreement, we have not experienced any work stoppages, and we believe that our relationship with our employees is good.

We recognize that attracting, motivating and retaining talent is vital to our continued success. We aim to create an equitable, inclusive and empowering environment in which our employees can grow and advance their careers, with the overall goal of developing, expanding and retaining our workforce to support our current pipeline and future business goals. We value innovation, passion, data-driven decision making, persistence and honesty, and are building a diverse environment where our employees and consultants can thrive and be inspired to make exceptional contributions.

Our current management team, board of directors, and scientific advisors have significant experience in development and marketing of pharmaceutical product candidates from early stage discovery to clinical trials, regulatory approval and commercialization.

Our human capital resources objectives include identifying, recruiting, retaining, and incentivizing our existing and new employees. We maintain an equity incentive plan, the principal purposes of which are to attract, retain and reward personnel through the granting of stock-based compensation awards, in order to increase stockholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives. To facilitate talent attraction and retention, we strive to make our company a safe and rewarding workplace, with opportunities for our employees to grow and develop in their careers, supported by competitive compensation, benefits and health and wellness programs, and by programs that build connections between our employees.

In addition, as a result of the COVID-19 pandemic, we have taken steps to protect the health and safety of our employees in line with directives from state and the applicable local governments, as well as guidance from the Centers for Disease Control.

An investment in our ~~common stock~~Common Stock, par value $0.001 per share (“Common Stock”) is highly speculative, involves a high degree of risk, and should be made only by investors who can afford a complete loss. You should carefully consider the following risk factors, together with the other information in this Annual Report on Form 10-K, including our financial statements and the related notes, before you decide to buy our ~~common stock.~~Common Stock. If any of the following risks actually occur, our business, financial condition, or results of operations could be materially adversely affected, the trading of our ~~common stock~~Common Stock could decline, and you may lose all or part of your investment therein.

Our business is subject to numerous risks and uncertainties, discussed in more detail in the following section. These risks include, among others, the following key risks:

~~Cardinal Health 414~~Risks Related to Clinical Development, Regulatory Approval and Commercialization, ~~SpePharm AG~~, ~~Sayre Therapeutics~~ ~~or Sinotau~~ ~~do not achieve commercial success with~~ ~~Tc99m~~ ~~tilmanocept~~,

We may have difficulty raising additional capital, which could deprive us of necessary resources to pursue our business plans.

We expect to devote significant capital resources to fund R&D and to maintain existing and secure new manufacturing resources. In order to support the initiatives envisioned in our business plan, we will likely need to raise additional funds through the sale of assets, public or private secured or unsecured debt or equity financing, collaborative relationships or other arrangements. Our ability to raise additional financing depends on many factors beyond our control, including the state of capital markets, the market price of our Common Stock and the development or prospects for development of competitive technology by others. Sufficient additional financing may not be available to us or may be available only on terms that would result in further dilution to the current owners of our Common Stock.

Our future expenditures on our programs are subject to many uncertainties, including whether our product candidates will be developed or commercialized with a partner or independently. Our future capital requirements will depend on, and could increase significantly as a result of, many factors, including:

Our ability to raise additional capital may also be adversely impacted by potential worsening global economic conditions and the recent disruptions to, and volatility in, financial markets in the United States and worldwide resulting from the ongoing COVID-19 pandemic and Ukraine conflict. In addition, on February 14, 2022, we filed a registration statement with the Securities and Exchange Commission to register the sale of up to $35 million of Company Common Stock pursuant to a rights offering to the Company’s stockholders, the terms and timing of which have not yet been determined by the Company. Further, there is no assurance that such rights offering will occur on any terms. If we are unsuccessful in raising additional capital, or the terms of raising such capital are unacceptable, we may have to modify our business plan and/or significantly curtail our planned development activities, acquisition of new product candidates and other operations.

There may be future sales or other dilution of our equity, which may adversely affect the market price of shares of our Common Stock.

Our existing warrants or other securities convertible into or exchangeable for our Common Stock, or securities we may issue in the future, may contain adjustment provisions that could increase the number of shares issuable upon exercise, conversion or exchange, as the case may be, and decrease the exercise, conversion or exchange price. The market price of our shares of Common Stock could decline as a result of sales of a large number of shares of our Common Stock or other securities in the market, the triggering of any such adjustment provisions or the perception that such sales could occur in the future.

Shares of Common Stock are equity securities and are subordinate to our existing and future indebtedness and preferred stock.

Shares of our Common Stock are common equity interests. This means that our Common Stock ranks junior to our Series D Preferred Stock and Series E Preferred Stock, to our indebtedness and to all creditor claims and other non-equity claims against us and our assets available to satisfy claims on us, including claims in a bankruptcy or similar proceeding. Our future indebtedness and preferred stock may restrict payments of dividends on our Common Stock.

Additionally, unlike indebtedness, where principal and interest customarily are payable on specified due dates, in the case of our Common Stock, (i) dividends are payable only when and if declared by our Board of Directors or a duly authorized committee of our Board of Directors, and (ii) as a corporation, we are restricted to making dividend payments and redemption payments out of legally available assets. We have never paid a dividend on our Common Stock and have no current intention to pay dividends in the future. Furthermore, our Common Stock places no restrictions on our business or operations or on our ability to incur indebtedness or engage in any transactions, subject only to the voting rights available to shareholders generally.

Our ability to continue as a going concern is dependent on a combination of several factors, including, our ability to raise capital by issuing debt or equity securities to investors, license or sell our product candidates to other pharmaceutical companies, and generate revenues from successfully developed products. If we are not able to continue our business as a going concern, we may be forced to liquidate our assets for an amount less than the value at which those assets are carried on our financial statements, and it is likely that investors will lose part or all of their investment.

The Company is currently engaged in litigation with Dr. Goldberg and CRG. In addition, the Company has experienced recurring net losses and has used significant cash to fund its operations. The Company has considerable discretion over the extent of development project expenditures and has the ability to curtail the related cash flows as needed. The Company also has funds remaining under outstanding grant awards, and continues working to establish new sources of funding, including collaborations, potential equity investments, and additional grant funding that can augment the balance sheet. However, the extent to which COVID-19 impacts our business will depend on future developments, which are highly uncertain and cannot be predicted, including new information which may emerge concerning the severity of COVID-19 and the actions to contain or treat its impact, among others. A significant outbreak of COVID-19 or other infectious diseases could result in a widespread health crisis that could adversely affect the economies and financial markets worldwide, resulting in an economic downturn that could impact our business, financial condition and results of operations, including our ability to obtain additional funding, if needed. Based on our current working capital and our projected cash burn, management believes that there is substantial doubt about the Company’s ability to continue as a going concern for a period of one year from the filing of this Annual Report on Form 10-K. No adjustments have been made to the accompanying consolidated financial statements of the Company as a result of this uncertainty.

If Cardinal Health 414, Sayre Therapeutics or Sinotau do not achieve commercial success with Tc99m tilmanocept, we may be unable to generate significant revenue from these relationships.

In March 2017, Navidea completed the ~~Asset Sale~~sale to Cardinal Health 414 ~~as discussed previously under “Development~~ of ~~the Business.” Pursuant to the Purchase Agreement, we sold~~ all of ~~our~~its assets ~~used, held for use, or intended to be~~ used in operating its business of developing, manufacturing and commercializing the ~~Business, including~~Company’s radioactive diagnostic agent marketed under the Lymphoseek trademark in Canada, Mexico and the United States. Upon closing of the ~~Asset Sale,~~sale, the Supply and Distribution Agreement between Cardinal Health 414 and the Company was ~~terminated.~~terminated and Cardinal Health 414 assumed responsibility for marketing Lymphoseek in those territories. Under the terms of the ~~Purchase Agreement,~~sale, Navidea is entitled to receive milestone payments (which, if paid, will be treated as additional purchase price) from Cardinal Health 414 based on net sales derived from Lymphoseek, subject, in each case, to Cardinal Health 414’s right to off-set.

Under the terms of our August 2014 agreement with Sinotau, as amended, Navidea is entitled to receive royalties and milestone payments based on Sinotau’s sales of Tc99m tilmanocept. Upon approval by the CFDA, Sinotau will be responsible for all Tc99m tilmanocept sales, marketing, market access and medical affairs activities in China, excluding Hong Kong, Macau and Taiwan. Tc99m tilmanocept has not yet received marketing approval in ~~China.~~

~~Under~~China, which may be delayed due to the terms of our March 2015 exclusive sublicense agreement with SpePharm, Navidea is entitled to receive royalty and milestone payments from SpePharm based on net sales derived from Tc99m tilmanocept. SpePharm commenced marketing of Tc99m tilmanoceptcoronavirus outbreak in ~~the EU during the third quarter of 2017.~~China.

Under the terms of our June 2017 agreement with Sayre, Navidea is eligible to receive milestone payments and royalties associated with the sale of Tc99m tilmanocept in India. Tc99m tilmanocept has not yet received marketing approval in India.

Cardinal Health 414, ~~SpePharm,~~ Sayre or Sinotau may never achieve commercial success in North America, ~~the EU,~~ India, China, or any other global market, they may never realize sales at levels necessary for us to achieve sales-based earnout, royalty or milestone ~~payments, and such payments may never lead to us becoming profitable.~~payments.

Risks Related to Clinical Development, Regulatory Approval and Commercialization

If we do not successfully develop any additional product candidates into marketable products, we may be unable to generate significant revenue or become profitable.

Additional diagnostic and therapeutic applications of the Manocept platform, including diagnosis of ~~other~~RA and CV disease and solid tumor cancers, ~~rheumatoid arthritis and cardiovascular disease,~~ among others, are in various stages of pre-clinical and clinical development. Regulatory approval of additional Manocept-based product candidates may not be successful, or if successful, may not result in ~~increased~~significant sales. Additional clinical testing for products based on our Manocept platform or other product candidates may not be successful and, even if they are, we may not be successful in developing any of them into a commercial product which will provide sufficient revenue to make us profitable.

Many companies in the pharmaceutical industry suffer significant setbacks in advanced clinical trials even after reporting promising results in earlier trials. Even if our Manocept trials are viewed as successful, we may not get regulatory approval for marketing of any Manocept product candidate. Our Manocept product candidates will be successful only if:

We are dependent on the achievement of a number of these goals in order to generate future revenues. The failure to generate revenues from our Manocept-based product candidates may preclude us from continuing our ~~research and development~~R&D of these and other product candidates.

We may never obtain regulatory approval to manufacture or market our unapproved drug candidates and our approval to market our products or anticipated commercial launch may be delayed as a result of the regulatory review process.

Obtaining regulatory approval to market drugs to diagnose or treat diseases is expensive, difficult and risky. Preclinical and clinical data, as well as information related to the chemistry, manufacturing and control (“CMC”) processes of drug production, can be interpreted in different ways that could delay, limit or preclude regulatory approval. Negative or inconclusive results, adverse medical events during a clinical trial, or issues related to CMC processes could also delay, limit or prevent regulatory approval. Even if we receive regulatory clearance to market a particular product candidate, the approval could be conditioned on us conducting additional costly post-approval studies or could limit the indicated uses included in our labeling.

We ~~may not~~ ~~be successful in securing and/or maintaining the necessary manufacturing, supply and/or radiolabeling capabilities for our product candidates in clinical development.~~

We may not be able to secure and/or maintain agreements or other purchasing arrangements with our subcontractors on terms acceptable to us, or that our subcontractors will be able to meet our production requirements on a timely basis, at the required levels of performance and quality, including compliance with FDA cGMP requirements. In the event that any of our subcontractors are unable or unwilling to meet our production requirements, we may not be able to establish an alternate source of supply without significant interruption in product supply or without significant adverse impact to product availability or cost. Any significant supply interruption or yield problems that we or our subcontractors experience would have a material adverse effect on our ability to manufacture our products and, therefore, a material adverse effect on our business, financial condition, and results of operations until a new source of supply is qualified.

Clinical trials for our product candidates will be lengthy and expensive,, and their outcome is uncertain.

Before obtaining regulatory approval for the commercial sale of any product candidates, we must demonstrate through preclinical testing and clinical trials that our product candidates are safe and effective for use in humans. Conducting clinical trials is a time consuming, expensive and uncertain process and may take years to complete.

We expect to sponsor efforts to explore the Manocept platform, whether in potential diagnostic or therapeutic uses. We continually assess our clinical trial plans and may, from time to time, initiate additional clinical trials to support our overall strategic development objectives. Historically, the results from preclinical testing and early clinical trials often do not predict the results obtained in later clinical trials. Frequently, drugs that have shown promising results in preclinical or early clinical trials subsequently fail to establish sufficient safety and efficacy data necessary to obtain regulatory approval. At any time during the clinical trials, we, the participating institutions, the FDA, the European Medicines Agency (“EMA”) or other regulatory authorities might delay or halt any clinical trials for our product candidates for various reasons, including:

While we have achieved some level of success in our clinical trials for Tc99m tilmanocept as indicated by the FDA and EMA approvals, the results of ~~pending~~current and future trials for other product candidates that we may develop or acquire, are subject to review and interpretation by various regulatory bodies during the regulatory review process and may ultimately fail to demonstrate the safety or effectiveness of our product candidates to the extent necessary to obtain regulatory approval, or that commercialization of our product candidates is worthwhile. Any failure or substantial delay in successfully completing clinical trials and obtaining regulatory approval for our product candidates could materially harm our business.

We extensively outsource our clinical trial activities and usually perform only a small portion of the start-up activities in-house. We rely on independent third-party contract research organizations (“CROs”) to perform most of our clinical studies, including document preparation, site identification, screening and preparation, pre-study visits, training, post-study audits and statistical analysis. Many important aspects of the services performed for us by the CROs are out of our direct control. If there is any dispute or disruption in our relationship with our CROs, our clinical trials may be delayed. Moreover, in our regulatory submissions, we rely on the quality and validity of the clinical work performed by third-party CROs. If any of our CROs’ processes, methodologies or results were determined to be invalid or inadequate, our own clinical data and results and related regulatory approvals could be adversely impacted.

Even if our drug candidates are successful in clinical trials, we may not be able to successfully commercialize them.

We have dedicated and will continue to dedicate substantially all of our resources to the ~~research and development (“~~R~~&D”)~~&D of our Manocept technology and related compounds. There are many difficulties and uncertainties inherent in pharmaceutical R&D and the introduction of new products. A high rate of failure is inherent in new drug discovery and development. The process to bring a drug from the discovery phase to regulatory approval can take 12 to 15 years or longer and cost more than $1 billion. Failure can occur at any point in the process, including late in the process after substantial investment. As a result, most research programs will not generate financial returns. New product candidates that appear promising in development may fail to reach the market or may have only limited commercial success. Delays and uncertainties in the regulatory approval processes in the United States and in other countries can result in delays in product launches and lost market opportunities. Consequently, it is very difficult to predict which products will ultimately be approved. Due to the risks and uncertainties involved in the R&D process, we cannot reliably estimate the nature, timing, completion dates, and costs of the efforts necessary to complete the development of our R&D projects, nor can we reliably estimate the future potential revenue that will be generated from a successful R&D project.

Prior to commercialization, each product candidate requires significant research, development and preclinical testing and extensive clinical investigation before submission of any regulatory application for marketing approval. The development of radiopharmaceutical technologies and compounds, including those we are currently developing, is unpredictable and subject to numerous risks. Potential products that appear to be promising at early stages of development may not reach the market for a number of reasons including that they may:

The occurrence of any of these events could adversely affect the commercialization of our product candidates. Products, if introduced, may not be successfully marketed and/or may not achieve customer acceptance. If we fail to commercialize products or if our future products do not achieve significant market acceptance, we will not likely generate significant revenues or become profitable.

If we fail to establish and maintain collaborations or if our partners do not perform, we may be unable to develop and commercialize our product candidates.

We have entered into collaborative arrangements with third parties to develop and/or commercialize product candidates and are currently seeking additional collaborations. Such collaborations might be necessary in order for us to fund our ~~research and development~~R&D activities and third-party manufacturing arrangements, seek and obtain regulatory approvals and successfully commercialize our existing and future product candidates. If we fail to enter into collaborative arrangements or fail to maintain our existing collaborative arrangements, the number of product candidates from which we could receive future revenues would decline.

Our dependence on collaborative arrangements with third parties will subject us to a number of risks that could harm our ability to develop and commercialize products including that:

The occurrence of any of these events could adversely affect the development or commercialization of our products.

Our pharmaceutical products will remain subject to ongoing regulatory review following the receipt of marketing approval. If we fail to comply with continuing regulations, we could lose these approvals and the sale of our products could be suspended.

Approved products may later cause adverse effects that limit or prevent their widespread use, force us to withdraw it from the market or impede or delay our ability to obtain regulatory approvals in additional countries. In addition, any contract manufacturer we use in the process of producing a product and its facilities will continue to be subject to FDA review and periodic inspections to ensure adherence to applicable regulations. After receiving marketing clearance, the manufacturing, labeling, packaging, adverse event reporting, storage, advertising, promotion and record-keeping related to the product will remain subject to extensive regulatory requirements. We may be slow to adapt, or we may never adapt, to changes in existing regulatory requirements or adoption of new regulatory requirements.

If we fail to comply with the regulatory requirements of the FDA and other applicable U.S. and foreign regulatory authorities or previously unknown problems with our products, manufacturers or manufacturing processes are discovered, we could be subject to administrative or judicially imposed sanctions, including:

If users of our products are unable to obtain adequate reimbursement from third-party ~~payers,~~payors, or if new restrictive legislation is adopted, market acceptance of our products may be limited and we may not achieve anticipated revenues.

Our ability to commercialize our products will depend in part on the extent to which appropriate reimbursement levels for the cost of our products and related treatment are obtained by governmental authorities, private health insurers and other organizations such as health maintenance organizations (“HMOs”). Generally, in Europe and other countries outside the United States, the government-sponsored healthcare system is the primary ~~payer~~payor of patients’ healthcare costs. Third-party ~~payers~~payors are increasingly challenging the prices charged for medical care. Also, the trend toward managed health care in the United States and the concurrent growth of organizations such as HMOs which could control or significantly influence the purchase of health care services and products, as well as legislative proposals to further reform health care or reduce government insurance programs, may all result in lower prices for our products if approved for commercialization. The cost containment measures that health care ~~payers~~payors and providers are instituting and the effect of any health care reform could materially harm our ability to sell our products at a profit.

We may be unable to establish or contract for the pharmaceutical manufacturing capabilities necessary to develop and commercialize our potential products.

We are in the process of establishing third-party ~~clinical~~ manufacturing capabilities for our compounds under development. We intend to rely on third-party contract manufacturers to produce sufficiently large quantities of drug materials that are and will be needed for clinical trials and commercialization of our potential products. Third-party manufacturers may not be able to meet our needs with respect to timing, quantity or quality of materials. If we are unable to contract for a sufficient supply of needed materials on acceptable terms, or if we should encounter delays or difficulties in our relationships with manufacturers, clinical trials for our product candidates may be delayed, thereby delaying the submission of product candidates for regulatory approval and the market introduction and subsequent commercialization of our potential products, and for approved products, any such delays, interruptions or other difficulties may render us unable to supply sufficient quantities to meet demand. Any such delays or interruptions may lower our revenues and potential profitability.

We and any third-party manufacturers that we may use must continually adhere to cGMPs and regulations enforced by the FDA through its facilities inspection program and/or foreign regulatory authorities where our products will be tested and/or marketed. If our facilities or the facilities of third-party manufacturers cannot pass a pre-approval plant inspection, the FDA and/or foreign regulatory authorities will not grant approval to market our product candidates. In complying with these regulations and foreign regulatory requirements, we and any of our third-party manufacturers will be obligated to expend time, money and effort on production, record-keeping and quality control to assure that our potential products meet applicable specifications and other requirements. The FDA and other regulatory authorities may take action against a contract manufacturer who violates cGMPs.

Our product supply and related patient access could be negatively impacted by, among other things: (i) product seizures or recalls or forced closings of manufacturing plants; (ii) disruption in supply chain continuity including from natural or man-made disasters at a critical supplier, as well as our failure or the failure of any of our suppliers to comply with cGMPs and other applicable regulations or quality assurance guidelines that could lead to manufacturing shutdowns, product shortages or delays in product manufacturing; (iii) manufacturing, quality assurance/quality control, supply problems or governmental approval delays; (iv) the failure of a sole source or single source supplier to provide us with the necessary raw materials, supplies or finished goods within a reasonable timeframe; (v) the failure of a third-party manufacturer to supply us with bulk active or finished product on time; and (vi) other manufacturing or distribution issues, including limits to manufacturing capacity due to regulatory requirements, and changes in the types of products produced, physical limitations or other business interruptions.

We may not be successful in securing and/or maintaining the necessary manufacturing, supply and/or radiolabeling capabilities for our product candidates in clinical development.

If any of our license agreements for intellectual property underlying our Manocept platform or any other products or potential products are terminated, we may lose the right to develop or market that product.

We have licensed intellectual property, including patents and patent applications relating to the underlying intellectual property for our Manocept platform, upon which all of our current product candidates are based. We may also enter into other license agreements or acquire other product candidates. The potential success of our product development programs depend on our ability to maintain rights under these licenses, including our ability to achieve development or commercialization milestones contained in the licenses. Under certain circumstances, the licensors have the power to terminate their agreements with us if we fail to meet our obligations under these licenses. We may not be able to meet our obligations under these licenses. If we default under any license agreement, we may lose our right to market and sell any products based on the licensed technology.

We may not have sufficient legal protection against infringement or loss of our intellectual property, and we may lose rights or protection related to our intellectual property if diligence requirements are not met, or at the expiry of underlying patents.

Our success depends, in part, on our ability to secure and maintain patent protection for our products and product candidates, to preserve our trade secrets, and to operate without infringing on the proprietary rights of third parties. While we seek to protect our proprietary positions by filing U.S. and foreign patent applications for our important inventions and improvements, domestic and foreign patent offices may not issue these patents. Third parties may challenge, invalidate, or circumvent our patents or patent applications in the future. Competitors, many of which have significantly more resources than we have and have made substantial investments in competing technologies, may apply for and obtain patents that will prevent, limit, or interfere with our ability to make, use, or sell our products either in the United States or abroad.

Numerous U.S. and foreign issued patents and pending patent applications, which are owned by third parties, exist in the fields in which we are or may be developing products. As the biotechnology and pharmaceutical industry expands and more patents are issued, the risk increases that we will be subject to claims that our products or product candidates, or their use, infringe the rights of others. In the United States, most patent applications are secret for a period of 18 months after filing, and in foreign countries, patent applications are secret for varying periods of time after filing. Publications of discoveries tend to significantly lag the actual discoveries and the filing of related patent applications. Third parties may have already filed applications for patents for products or processes that will make our products obsolete, limit our patents, invalidate our patent applications or create a risk of infringement claims.

Under U.S. patent law, we are currently subject to a “first to file” system of patent approval, as opposed to the former “first to invent” system. As a consequence, delays in filing patent applications for new product candidates or discoveries could result in the loss of patentability if there is an intervening patent application with similar claims filed by a third party, even if we or our collaborators were the first to invent.

We or our suppliers may be exposed to, or threatened with, future litigation by third parties having patent or other intellectual property rights alleging that our products, product candidates and/or technologies infringe their intellectual property rights or that the process of manufacturing our products or any of their respective component materials, or the component materials themselves, or the use of our products, product candidates or technologies, infringe their intellectual property rights. If one of these patents was found to cover our products, product candidates, technologies or their uses, or any of the underlying manufacturing processes or components, we could be required to pay damages and could be unable to commercialize our products or use our technologies or methods unless we are able to obtain a license to the patent or intellectual property right. A license may not be available to us in a timely manner or on acceptable terms, if at all. In addition, during litigation, a patent holder could obtain a preliminary injunction or other equitable remedy that could prohibit us from making, using or selling our products, technologies or methods.

Our currently held and licensed patents expire over the next three to fifteen years. Expiration of the patents underlying our technology, in the absence of extensions or other trade secret or intellectual property protection, may have a material and adverse effect on us.

In addition, it may be necessary for us to enforce patents under which we have rights, or to determine the scope, validity and unenforceability of other parties’ proprietary rights, which may affect our rights. There can be no assurance that our patents would be held valid by a court or administrative body or that an alleged infringer would be found to be infringing. The uncertainty resulting from the mere institution and continuation of any patent related litigation or interference proceeding could have a material and adverse effect on us.

We typically require our employees, consultants, advisers and suppliers to execute confidentiality and assignment of invention agreements in connection with their employment, consulting, advisory, or supply relationships with us. They may breach these agreements and we may not obtain an adequate remedy for breach. Further, third parties may gain unauthorized access to our trade secrets or independently develop or acquire the same or equivalent information.

We and our collaborators may not be able to protect our intellectual property rights throughout the world.

Filing, prosecuting and defending patents on all of our product candidates and products, when and if we have any, in every jurisdiction would be prohibitively expensive. Competitors may use our technologies in jurisdictions where we or our licensors have not obtained patent protection to develop their own products. These products may compete with our products, when and if we have any, and may not be covered by any of our or our licensors' patent claims or other intellectual property rights.

The laws of some foreign countries do not protect intellectual property rights to the same extent as the laws of the United States, and many companies have encountered significant problems in protecting and defending such rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to biotechnology and/or pharmaceuticals, which could make it difficult for us to stop the infringement of our patents. Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial cost and divert our efforts and attention from other aspects of our business.

The intellectual property protection for our product candidates depends on third parties.

With respect to Manocept and NAV4694, we have licensed certain issued patents and pending patent applications covering the respective technologies underlying these product candidates and their commercialization and use and we have licensed certain issued patents and pending patent applications directed to product compositions and chemical modifications used in product candidates for commercialization, and the use and the manufacturing thereof.

The patents and pending patent applications underlying our licenses do not cover all potential product candidates, modifications and uses. In the case of patents and patent applications licensed from UCSD, we did not have any control over the filing of the patents and patent applications before the effective date of the Manocept licenses, and had limited control over the filing and prosecution of these patents and patent applications after the effective date of such licenses. In the case of patents and patent applications licensed from AstraZeneca, we have limited control over the filing, prosecution or enforcement of these patents or patent applications. We cannot be certain that such prosecution efforts have been or will be conducted in compliance with applicable laws and regulations or will result in valid and enforceable patents. We also cannot be assured that our licensors or their respective licensing partners will agree to enforce any such patent rights at our request or devote sufficient efforts to attain a desirable result. Any failure by our licensors or any of their respective licensing partners to properly protect the intellectual property rights relating to our product candidates could have a material adverse effect on our financial condition and results of operation.

We may become involved in disputes with licensors or potential future collaborators over intellectual property ownership, and publications by our research collaborators and scientific advisors could impair our ability to obtain patent protection or protect our proprietary information, which, in either case, could have a significant effect on our business.

Inventions discovered under research, material transfer or other such collaborative agreements may become jointly owned by us and the other party to such agreements in some cases and the exclusive property of either party in other cases. Under some circumstances, it may be difficult to determine who owns a particular invention, or whether it is jointly owned, and disputes could arise regarding ownership of those inventions. These disputes could be costly and time consuming and an unfavorable outcome could have a significant adverse effect on our business if we were not able to protect our license rights to these inventions. In addition, our research collaborators and scientific advisors generally have contractual rights to publish our data and other proprietary information, subject to our prior review. Publications by our research collaborators and scientific advisors containing such information, either with our permission or in contravention of the terms of their agreements with us, may impair our ability to obtain patent protection or protect our proprietary information, which could significantly harm our business.

A pandemic, epidemic or outbreak of an infectious disease may adversely affect our business.

If a pandemic, epidemic or outbreak of an infectious disease occurs in the United States or worldwide, our development and commercialization efforts may be adversely affected. In December 2019, a novel strain of coronavirus, COVID-19, was identified in Wuhan, China. In January 2020, the World Health Organization declared this outbreak a “Public Health Emergency of International Concern,” and the U.S. Department of Health and Human Services declared a public health emergency to aid the U.S. healthcare community in responding to COVID-19. The spread of COVID-19 has impacted the global economy and our operations, including the interruption of our clinical trial activities in Europe and regulatory approval process in India. For example, the COVID-19 outbreak delayed enrollment in our NAV3-32 clinical study in the United Kingdom due to national COVID-19-related shutdowns in early 2021. Our clinical trial activities may be further delayed due to prioritization of hospital resources toward the outbreak, and some patients may be unwilling to enroll in our trials or be unable to comply with clinical trial protocols if quarantines impede patient movement or interrupt healthcare services, which would delay our ability to conduct clinical trials or release clinical trial results, and could delay our ability to obtain regulatory approval and commercialize our product candidates. The spread of an infectious disease, including COVID-19, may also result in the inability of our suppliers to deliver clinical drug supplies on a timely basis or at all. In addition, hospitals may reduce staffing and reduce or postpone certain treatments in response to the spread of an infectious disease. Such events may result in a period of business disruption, and in reduced operations, or doctors and medical providers may be unwilling to participate in our clinical trials, any of which could materially affect our business, financial condition and results of operations. The extent to which the global COVID-19 pandemic impacts our business will depend on future developments, which are highly uncertain and cannot be predicted, including new information that may emerge concerning the severity of COVID-19 and the actions to contain or treat its impact, among others. Any significant infectious disease outbreak, including the COVID-19 pandemic, could result in a widespread health crisis that could adversely affect the economies and financial markets worldwide, resulting in an economic downturn that could impact our business, financial condition and results of operations, including our ability to obtain additional funding, if needed. The Company has enhanced its business continuity plans to include measures to protect our employees in the event of infection in our corporate offices, or in response to potential mandatory quarantines.

The biotech and pharmaceutical industries are intensely competitive. Many of our competitors have significantly greater financial, technical, manufacturing, marketing and distribution resources as well as greater experience in the industry than we have. The particular medical conditions our product lines address can also be addressed by other medical procedures or drugs. Many of these alternatives are widely accepted by physicians and have a long history of use.

To remain competitive, we must continue to launch new products and technologies. To accomplish this, we commit substantial efforts, funds, and other resources to ~~research and development.~~R&D. A high rate of failure is inherent in the ~~research and development~~R&D of new products and technologies. We must make ongoing substantial expenditures without any assurance that our efforts will be commercially successful. Failure can occur at any point in the process, including after significant funds have been invested. Promising new product candidates may fail to reach the market or may only have limited commercial success because of efficacy or safety concerns, failure to achieve positive clinical outcomes, inability to obtain necessary regulatory approvals, limited scope of approved uses, excessive costs to manufacture, the failure to establish or maintain intellectual property rights, or infringement of the intellectual property rights of others. Even if we successfully develop new products or enhancements or new generations of our existing products, they may be quickly rendered obsolete by changing customer preferences, changing industry standards, or competitors' innovations. Innovations may not be accepted quickly in the marketplace because of, among other things, entrenched patterns of clinical practice or uncertainty over third-party reimbursement. We cannot state with certainty when or whether any of our products under development will be launched, whether we will be able to develop, license, or otherwise acquire compounds or products, or whether any products will be commercially successful. Failure to launch successful new products or new indications for existing products may cause our products to become obsolete, causing our revenues and operating results to suffer.

Physicians may use our competitors’ products and/or our products may not be competitive with other technologies. Tc99m tilmanocept is expected to continue to compete against sulfur colloid in the United States and other colloidal agents in the EU and other global markets. If our competitors are successful in establishing and maintaining market share for their products, our future earnout and royalty receipts may not occur at the rate we anticipate. In addition, our potential competitors may establish cooperative relationships with larger companies to gain access to greater ~~research and development~~R&D or marketing resources. Competition may result in price reductions, reduced gross margins and loss of market share.

We may be exposed to business risk, including product liability claims for any product candidates and products that we are able to commercialize.

The testing, manufacturing, marketing and use of any commercial products that we develop, as well as product candidates in development, involve substantial risk of product liability claims. These claims may be made directly by consumers, healthcare providers, pharmaceutical companies or others. In recent years, coverage and availability of cost-effective product liability insurance has decreased, so we may be unable to maintain sufficient coverage for product liabilities that may arise. In addition, the cost to defend lawsuits or pay damages for product liability claims may exceed our coverage. If we are unable to maintain adequate coverage or if claims exceed our coverage, our financial condition and our ability to clinically test our product candidates and market our products will be adversely impacted. In addition, negative publicity associated with any claims, regardless of their merit, may decrease the future demand for our products and impair our financial condition.

The administration of drugs in humans, whether in clinical studies or commercially, carries the inherent risk of product liability claims whether or not the drugs are actually the cause of an injury. Our products or product candidates may cause, or may appear to have caused, injury or dangerous drug interactions, and we may not learn about or understand those effects until the product or product candidate has been administered to patients for a prolonged period of time. We may be subject from time to time to lawsuits based on product liability and related claims, and we cannot predict the eventual outcome of any future litigation. We may not be successful in defending ourselves in the litigation and, as a result, our business could be materially harmed. These lawsuits may result in large judgments or settlements against us, any of which could have a negative effect on our financial condition and business if in excess of our insurance coverage. Additionally, lawsuits can be expensive to defend, whether or not they have merit, and the defense of these actions may divert the attention of our management and other resources that would otherwise be engaged in managing our business.

As a result of a number of factors, product liability insurance has become less available while the cost has increased significantly. We currently carry product liability insurance that our management believes is appropriate given the risks that we face. We will continually assess the cost and availability of insurance; however, there can be no guarantee that insurance coverage will be obtained or, if obtained, will be sufficient to fully cover product liabilities that may arise. If we are held liable for a claim against which we are not insured or for damages exceeding the limits of our insurance coverage, whether arising out of product liability matters, cybersecurity matters, or from some other matter, that claim could have a material adverse effect on our results of operations.

Security breaches and other disruptions could compromise our information and expose us to liability, which would cause our business and reputation to suffer.

In the ordinary course of our business, we collect and store sensitive data, including intellectual property, our proprietary business information and that of our suppliers and business partners, and personally identifiable information of employees and clinical trial subjects, in our data centers and on our networks. The secure maintenance and transmission of this information is critical to our operations and business strategy. Despite our security measures, our information technology and infrastructure may be vulnerable to attacks by hackers or breached due to employee error, malfeasance or other disruptions. Any such breach could compromise our networks and the information stored there could be accessed, publicly disclosed, lost or stolen. Any such access, disclosure or other loss of information could result in legal claims or proceedings, liability under laws that protect the privacy of personal information, and regulatory penalties, disrupt our operations, and damage our reputation, which could adversely affect our business, revenues and competitive position.

Failure to comply with domestic and international privacy and security laws can result in the imposition of significant civil and criminal penalties. The costs of compliance with these laws, including protecting electronically stored information from cyber-attacks, and potential liability associated with failure to do so could adversely affect our business, financial condition and results of operations. We are subject to various domestic and international privacy and security regulations, including but not limited to The Health Insurance Portability and Accountability Act of 1996 (“HIPAA”). HIPAA mandates, among other things, the adoption of uniform standards for the electronic exchange of information in common healthcare transactions, as well as standards relating to the privacy and security of individually identifiable health information, which require the adoption of administrative, physical and technical safeguards to protect such information. In addition, many states have enacted comparable laws addressing the privacy and security of health information, some of which are more stringent than HIPAA.

A security breach or privacy violation that leads to disclosure of consumer information (including personally identifiable information or protected health information) could harm our reputation, compel us to comply with disparate state and foreign breach notification laws and otherwise subject us to liability under laws that protect personal data, resulting in increased costs or loss of revenue.

Despite our efforts to protect against cyber-attacks and security breaches, hackers and other cyber criminals are using increasingly sophisticated and constantly evolving techniques, and we may need to expend substantial additional resources to continue to protect against potential security breaches or to address problems caused by such attacks or any breach of our safeguards. In addition, a data security breach could distract management or other key personnel from performing their primary operational duties.

The interpretation and application of consumer and data protection laws in the United States, Europe and elsewhere are often uncertain, contradictory and in flux. Among other things, foreign privacy laws impose significant obligations on U.S. companies to protect the personal information of foreign citizens. It is possible that these laws may be interpreted and applied in a manner that is inconsistent with our data practices, which could have a material adverse effect on our business. Complying with these various laws could cause us to incur substantial costs or require us to change our business practices in a manner adverse to our business.

We ~~do not currently~~ carry cyber risk ~~insurance. If we are subject~~insurance, which may limit our exposure to liability resulting from a security breach or other disruption in our information ~~systems,~~systems; however, we ~~could be exposed to significant liability~~cannot assure you that ~~could have a material adverse effect on~~such insurance policy will cover all liabilities that may result from security breaches or other disruption in our ~~results of operations.~~information systems.

We are subject to domestic and foreign anticorruption laws, the violation of which could expose us to liability, and cause our business and reputation to suffer.

We are subject to the U.S. Foreign Corrupt Practices Act and similar anti-corruption laws in other jurisdictions. These laws generally prohibit companies and their intermediaries from engaging in bribery or making other prohibited payments to government officials for the purpose of obtaining or retaining business, and some have record keeping requirements. The failure to comply with these laws could result in substantial criminal and/or monetary penalties. We operate in jurisdictions that have experienced corruption, bribery, pay-offs and other similar practices from time-to-time and, in certain circumstances, such practices may be local custom. We have implemented internal control policies and procedures that mandate compliance with these anti-corruption laws. However, we cannot be certain that these policies and procedures will protect us against liability. If our employees or other agents engage in such conduct, we might be held responsible and we could suffer severe criminal or civil penalties and other consequences that could have a material adverse effect on our business, financial position, results of operations and/or cash flow, and the market value of our ~~common stock~~Common Stock could decline.

Our international operations expose us to economic, legal, regulatory and currency risks.

Our operations extend to countries outside the United States, and are subject to the risks inherent in conducting business globally and under the laws, regulations, and customs of various jurisdictions. These risks include: (i) failure to comply with a variety of national and local laws of countries in which we do business, including restrictions on the import and export of certain intermediates, drugs, and technologies, (ii) failure to comply with a variety of U.S. laws including the Iran Threat Reduction and Syria Human Rights Act of 2012; and rules relating to the use of certain “conflict minerals” under Section 1502 of the Dodd-Frank Wall Street Reform and Consumer Protection Act, (iii) changes in laws, regulations, and practices affecting the pharmaceutical industry and the health care system, including but not limited to imports, exports, manufacturing, quality, cost, pricing, reimbursement, approval, inspection, and delivery of health care, (iv) fluctuations in exchange rates for transactions conducted in currencies other than the functional currency, (v) adverse changes in the economies in which we or our partners and suppliers operate as a result of a slowdown in overall growth, a change in government or economic policies, or financial, political, or social change or instability in such countries that affects the markets in which we operate, particularly emerging markets, (vi) differing local product preferences and product requirements, (vii) changes in employment laws, wage increases, or rising inflation in the countries in which we or our partners and suppliers operate, (viii) supply disruptions, and increases in energy and transportation costs, (ix) natural disasters, including droughts, floods, and earthquakes in the countries in which we operate, (x) local disturbances, terrorist attacks, riots, social disruption, or regional hostilities in the countries in which we or our partners and suppliers operate and (xi) government uncertainty, including as a result of new or changed laws and regulations. We also face the risk that some of our competitors have more experience with operations in such countries or with international operations generally and may be able to manage unexpected crises more easily. Furthermore, whether due to language, cultural or other differences, public and other statements that we make may be misinterpreted, misconstrued, or taken out of context in different jurisdictions. Moreover, the internal political stability of, or the relationship between, any country or countries where we conduct business operations may deteriorate. Changes in a country’s political stability or the state of relations between any such countries are difficult to predict and could adversely affect our operations, profitability and/or adversely impact our ability to do business there. The occurrence of any of the above risks could have a material adverse effect on our business, financial position, results of operations and/or cash flow, and could cause the market value of our ~~common stock~~Common Stock to decline.

~~We may have difficulty raising additional capital, which could deprive us of necessary resources to pursue our business plans.~~

We expect to devote significant capital resources to fund research and development, to maintain existing and secure new manufacturing resources, and potentially to acquire new product candidates. In order to support the initiatives envisioned in our business plan, we will likely need to raise additional funds through the sale of assets, public or private debt or equity financing, collaborative relationships or other arrangements. Our ability to raise additional financing depends on many factors beyond our control, including the state of capital markets, the market price of our common stock and the development or prospects for development of competitive technology by others. Sufficient additional financing may not be available to us or may be available only on terms that would result in further dilution to the current owners of our common stock.

If we are unsuccessful in raising additional capital, or the terms of raising such capital are unacceptable, we may have to modify our business plan and/or significantly curtail our planned development activities, acquisition of new product candidates and other operations.

~~There may be future sales or other dilution of our equity, which may adversely affect the market price of shares of our common stock.~~

Our existing warrants or other securities convertible into or exchangeable for our common stock, or securities we may issue in the future, may contain adjustment provisions that could increase the number of shares issuable upon exercise, conversion or exchange, as the case may be, and decrease the exercise, conversion or exchange price. The market price of our shares of common stock could decline as a result of sales of a large number of shares of our common stock or other securities in the market, the triggering of any such adjustment provisions or the perception that such sales could occur in the future.

~~Shares of common stock are equity securities and are subordinate to our existing and future indebtedness and preferred stock.~~

Shares of our common stock are common equity interests. This means that our common stock ranks junior to any preferred stock that we may issue in the future, to our indebtedness and to all creditor claims and other non-equity claims against us and our assets available to satisfy claims on us, including claims in a bankruptcy or similar proceeding. Our future indebtedness and preferred stock may restrict payments of dividends on our common stock.

Additionally, unlike indebtedness, where principal and interest customarily are payable on specified due dates, in the case of our common stock, (i) dividends are payable only when and if declared by our Board of Directors or a duly authorized committee of our Board of Directors, and (ii) as a corporation, we are restricted to making dividend payments and redemption payments out of legally available assets. We have never paid a dividend on our common stock and have no current intention to pay dividends in the future. Furthermore, our common stock places no restrictions on our business or operations or on our ability to incur indebtedness or engage in any transactions, subject only to the voting rights available to shareholders generally.

The continuing contentious federal budget negotiations may have an impact on our business and financial condition in ways that we currently cannot predict, and may further limit our ability to raise additional funds.

The continuing federal budget disputes not only may adversely affect financial markets, but could also delay or reduce research grant funding and adversely affect operations of government agencies that regulate us, including the FDA, potentially causing delays in obtaining key regulatory approvals. Research funding for life science research has increased more slowly during the past several years compared to previous years and has declined in some countries, and some grants have been frozen for extended periods of time or otherwise become unavailable to various institutions, sometimes without advance notice. Government funding of research and development is subject to the political process, which is inherently fluid and unpredictable. Other programs, such as homeland security or defense, or general efforts to reduce the federal budget deficit could be viewed by the U.S. government as a higher priority. These budgetary pressures may result in reduced allocations to government agencies that fund research and development activities. National Institute of Health and other research and development allocations have been diminished in recent years by federal budget control efforts. The prolonged or increased shift away from the funding of life sciences research and development or delays surrounding the approval of government budget proposals may result in reduced research grant funding, which could delay development of our product candidates.

Our failure to maintain continued compliance with the listing requirements of the NYSE American exchange could result in the delisting of our ~~common stock.~~Common Stock.

Our ~~common stock~~Common Stock has been listed on the NYSE American exchange since February 2011. The rules of NYSE American provide that shares be delisted from trading in the event the financial condition and/or operating results of the Company appear to be unsatisfactory, the extent of public distribution or the aggregate market value of the ~~common stock~~Common Stock has become so reduced as to make further dealings on the NYSE American inadvisable, the Company has sold or otherwise disposed of its principal operating assets, or has ceased to be an operating company, or the Company has failed to comply with its listing agreements with the ~~Exchange.~~NYSE American. For example, the NYSE American may consider suspending trading in, or removing the listing of, securities of an issuer that has stockholders’ equity of less than (i) ~~$6.0~~$2.0 million if such issuer has sustained losses from continuing operations and/or net losses in two of its ~~five~~three most recent fiscal years, (ii) $4.0 million if such issuer has sustained losses from continuing operations and/or net losses in three of its four most recent fiscal years, and (iii) ~~$2.0~~$6.0 million if such issuer has sustained losses from continuing operations and/or net losses in ~~two of~~ its ~~three~~five most recent fiscal years. As of December 31, ~~2018~~2021 and ~~2017,~~2020, Navidea had stockholders’ equity of approximately ~~$1.7~~$625,000 and $2.0 million, ~~and $11.4 million,~~ respectively. ~~In addition, the Company had stockholders’ deficits for several years prior to December 31, 2017, and~~

On January 28, 2022, we ~~may not be able to maintain stockholders’ equity in the future. Even if an issuer has~~received a ~~stockholders’ deficit,~~deficiency letter from the NYSE American will not normally consider delisting securities of an issuer that fails to meet these requirements if the issuer has (1) average global market capitalization of at least $50,000,000; or total assets and revenue of $50,000,000 in its last fiscal year, or in two of its last three fiscal years; and (2) the issuer has at least 1,100,000 shares publicly held, a market value of publicly held shares of at least $15,000,000 and 400 round lot shareholders. As of December 31, 2018, the Company’s total value of market capitalization was approximately $19.4 million. Therefore, we do not currently meet these exceptions and there is a risk that our common stock may be delisted as a result of our failure to meet the minimum stockholders' equity requirement for continued listing. The NYSE American provides for an 18-month “cure period” for the Company to regain the minimum stockholders’ equity requirement, however if the Company is unable to do so, the NYSE American may delist the Company’s common stock.

The NYSE American Company Guide also provides that the Exchange may suspend or remove from listing any common stock selling for a substantial period of time at a low price per share, if the issuer shall fail to effect a reverse split of such shares within a reasonable time after being notified that the Exchange deems such action to be appropriate under all the circumstances. The Company’s common stock has recently traded for a price as low as $0.10 per share.

~~On August 14, 2018, the Company received a Deficiency Letter from the NYSE American~~LLC stating that Navidea was not in compliance with a certain NYSE American continued listing ~~standards~~standard relating to stockholders’ equity. Specifically, the ~~Deficiency Letter~~deficiency letter stated that Navidea is not in compliance with Section 1003(a)(ii) of the NYSE American Company Guide, which requires an issuer to have stockholders’ equity of $4.0 million or more if it has reported losses from continuing operations and/or net losses in three of its four most recent fiscal years. The Deficiency Letter noted that Navidea had stockholders’ equity of $2.1 million as of June 30, 2018, and has reported net losses in four of its five most recent fiscal years ended December 31, 2017.

Navidea was required to submit a plan to the NYSE American by September 14, 2018 advising of actions it has taken or will take to regain compliance with the continued listing standards by February 14, 2020. Navidea submitted a plan by the deadline.

On October 25, 2018, the Company received an Acceptance Letter from the NYSE American that the Company’s plan to regain compliance was accepted. The Acceptance Letter also stated that the NYSE American had inadvertently omitted an additional deficiency from the Deficiency Letter. Specifically, the Deficiency Letter should have stated that Navidea iswe are not in compliance with Section 1003(a)(iii) of the NYSE American Company Guide, which requires an issuer to have stockholders’ equity of $6.0 million or more if it has reported losses from continuing operations and/or net losses in its five most recent fiscal years. The ~~Acceptance Letter~~deficiency letter noted that ~~Navidea~~we had stockholders’ equity of ~~$2.1~~$4.1 million as of ~~June~~September 30, ~~2018,~~2021, and ~~has~~ reported net losses from continuing operations ~~and/or net losses~~ in ~~its~~our five most recent fiscal years ended December 31, ~~2017.~~2020.

~~The Company must provide quarterly updates~~We submitted a plan to the NYSE American ~~Staff concurrent with its interim/annual SEC filings. If Navidea fails~~on February 28, 2022 advising of actions we have taken or will take to regain compliance with the ~~stockholders’ equity~~continued listing standards by ~~February 14, 2020,~~July 28, 2023. If our plan is not accepted, or if we do not make progress consistent with the plan, or if we otherwise fail to regain compliance by the deadline, the NYSE American may commence delisting procedures.

In addition, the Deficiency Letter stated that the Staff determined that the Company’s securities have been selling for a low price per share for a substantial period of time and, pursuant to Section 1003(f)(v) of the NYSE American Company Guide, Navidea’s continued listing There is predicated on it effecting a reverse stock split of its Common Stock or otherwise demonstrating sustained price improvement within a reasonable period of time, which the Staff had determined to be no later than February 14, 2019. However, on January 28, 2019, the Company received a notice from the NYSE American that it has granted the Company an extension until March 31, 2019 to regain compliance with Section 1003(f)(v) of the NYSE American’s continued listing standards. Navidea must regain compliance with the price standard by that date in order to be considered for continued trading through the end of February 14, 2020.

At the Company’s 2018 Annual Meeting of Stockholders (the “Annual Meeting”), held on August 16, 2018, stockholders approved a reverse stock split of the Company’s common stock, as determined by the Board of Directors at its discretion, of a ratio of not less than one-for-five and not more than one-for-twenty. The Board of Directors has not taken action to effect a reverse stock split as of the date of filing this Annual Report on Form 10-K. There can be no assurance that we will meet the ~~Board of Directors will take steps to implement the reverse stock split, and if they do, such a reverse stock split may not be sufficient to enable the Company to maintain its~~continued listing ~~on the NYSE American. Therefore, there is a continued risk that the shares will be delisted if action is not taken to the satisfaction of the NYSE American.~~standard.

~~Navidea’s Common Stock~~Our common stock will continue to be listed on the NYSE American while ~~it attempts~~we attempt to regain compliance with the listing ~~standards~~standard noted, ~~above,~~ subject to ~~Navidea’s~~our compliance with other continued listing requirements. ~~The Common Stock~~Our common stock will continue to trade under the symbol “NAVB,” but will have an added designation of “.BC” to indicate that ~~Navidea is~~we are not in compliance with the NYSE American’s listing standards. The NYSE American notification does not affect ~~Navidea’s~~our business operations or ~~its~~our SEC reporting requirements and does not conflict with or cause an event of default under any of ~~Navidea’s~~our material agreements.

The delisting of our common stock from the NYSE American likely would reduce the trading volume and liquidity in our common stock and may lead to decreases in the trading price of our common stock. The delisting of our common stock may also materially impair our stockholders’ ability to buy and sell shares of our common stock. In addition, the delisting of our common stock could significantly impair our ability to raise capital.

The price of our ~~common stock~~Common Stock has been, and may continue to be, highly volatile, ~~due to several factors that will continue to affect~~and the ~~price~~value of ~~our stock.~~your investment could decline significantly.

Our ~~common stock~~Common Stock traded as low as ~~$0.10~~$0.72 per share and as high as ~~$0.42~~$2.65 per share during the 12-month period ended February 28, ~~2019.~~ 2022.

The ~~market price~~following factors, some of which are beyond our common stock has been and is expected to continue to be highly volatile. Factors, including announcements of technological innovations by us or other companies, regulatory matters, new or existing products or procedures, concerns about our financial position, operating results, litigation, government regulation, developments or disputes relating to agreements, patents or proprietary rights,control, may have a significant impact on the market price of our ~~stock. In addition, potential dilutive effects of future sales of shares of~~ common ~~stock by the Company and by stockholders, and subsequent sale of common stock by the holders of warrants and options could have an adverse effect on the market price of our shares.~~

~~Some additional factors which could lead to the volatility of our common stock include:~~stock:

~~The realization of any of the foregoing could have a dramatic~~These factors may materially and ~~adverse impact on~~adversely affect the market price of our common stock. In addition, class action litigation has often been instituted against companies whose securities have experienced substantial decline in market price. Moreover, regulatory entities often undertake investigations of investor transactions in securities that experience volatility following an announcement of a significant event or condition. Any such litigation brought against us or any such investigation involving our investorsstock, which could result in substantial ~~costs and a diversion of management’s attention and resources, which could hurt~~losses by our ~~business, operating results and financial condition.~~investors.

In addition, the stock market has experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of companies like ours. Broad market and industry factors may negatively affect the market price of our common stock, regardless of our actual operating performance. Further, a systemic decline in the financial markets and related factors beyond our control may cause our share price to decline rapidly and unexpectedly. Price volatility of our common stock might be worse if the trading volume of our ordinary shares is low.

An ~~investor’s~~investor’s ability to trade our ~~common stock~~Common Stock may be limited by trading volume.

During the 12-month period beginning on March 1, ~~2018~~2021 and ending on February 28, ~~2019,~~2022, the average daily trading volume for our ~~common stock~~Common Stock on the NYSE American was approximately ~~450,000~~117,000 shares. However, this trading volume may not be consistently maintained in the future. If the trading volume for our ~~common stock~~Common Stock decreases, there could be a relatively limited market for our ~~common stock~~Common Stock and the share price of our ~~common stock~~Common Stock would be more likely to be affected by broad market fluctuations, general market conditions, fluctuations in our operating results, changes in the market’s perception of our business and announcements made by us, our competitors or parties with whom we have business relationships. There may also be fewer institutional investors willing to hold or acquire our ~~common stock.~~Common Stock. Such a lack of liquidity in our ~~common stock~~Common Stock may make it difficult for us to issue additional securities for financing or other purposes or to otherwise arrange for any financing that we may need in the future.

The market price of our ~~common stock~~Common Stock may be adversely affected by market conditions affecting the stock markets in general, including price and trading fluctuations on the NYSE American exchange.

The market price of our ~~common stock~~Common Stock may be adversely affected by market conditions affecting the stock markets in general, including price and trading fluctuations on the NYSE American. These conditions may result in (i) volatility in the level of, and fluctuations in, the market prices of stocks generally and, in turn, our shares of ~~common stock,~~Common Stock, and (ii) sales of substantial amounts of our ~~common stock~~Common Stock in the market, in each case that could be unrelated or disproportionate to changes in our operating performance.

Because we do not expect to pay dividends on our ~~common stock~~Common Stock in the foreseeable future, stockholders will only benefit from owning ~~common stock~~Common Stock if it appreciates.

We have paid no cash dividends on any of our ~~common stock~~Common Stock to date, and we currently intend to retain our future earnings, if any, to fund the development and growth of our business. As a result, with respect to our ~~common stock,~~Common Stock, we do not expect to pay any cash dividends in the foreseeable future, and payment of cash dividends, if any, will also depend on our financial condition, results of operations, capital requirements and other factors and will be at the discretion of our Board of Directors. Furthermore, we are subject to various laws and regulations that may restrict our ability to pay dividends and we may not pay dividends on our Common Stock without the consent of a majority of the holders of the outstanding Series E Preferred Stock. We may also in the future become subject to contractual restrictions on, or prohibitions against, the payment of dividends. Due to our intent to retain any future earnings rather than pay cash dividends on our ~~common stock~~Common Stock and applicable laws, regulations and contractual obligations that may restrict our ability to pay dividends on our ~~common stock,~~Common Stock, the success of your investment in our ~~common stock~~Common Stock will likely depend entirely upon any future appreciation and there is no guarantee that our ~~common stock~~Common Stock will appreciate in value.

Our future ability to utilize our net operating loss carryforwards and certain other tax attributes may be limited.

We have incurred substantial losses during our history, and we may never achieve profitability. To the extent that we continue to generate taxable losses, unused losses will carry forward to offset a portion of future taxable income, if any, subject to expiration of such carryforwards in the case of carryforwards generated prior to 2018. Additionally, we continue to generate business tax credits, including research and development tax credits, which generally may be carried forward to offset a portion of future taxable income, if any, subject to expiration of such credit carryforwards. Under Sections 382 and 383 of the Internal Revenue Code, if a corporation undergoes an “ownership change,” generally defined as a greater than 50 percentage point change (by value) in its equity ownership over a three-year period, the corporation’s ability to use its pre-change net operating loss carryforwards (“NOLs”), and other pre-change tax attributes (such as research and development tax credits) to offset its post-change income or taxes may be limited. The Company completed a Section 382 analysis through December 31, 2021 and believes that a Section 382 ownership change has not occurred. However, we may experience additional ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which are outside of our control. As a result, if we earn net taxable income, our ability to use our pre-change NOLs or other pre-change tax attributes to offset U.S. federal taxable income may be subject to limitations, which could potentially result in increased future tax liability to us. Additionally, for taxable years beginning after December 31, 2017, the deductibility of such U.S. federal net operating losses is limited to 80% of our taxable income in any future taxable year. There is a risk that due to changes under the Tax Cuts and Jobs Act, regulatory changes, or other unforeseen reasons, our existing NOLs or business tax credits could expire or otherwise be unavailable to offset future income tax liabilities. At the state level, there may also be periods during which the use of NOLs or business tax credits is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed. For these reasons, we may not be able to realize a tax benefit from the use of our NOLs or tax credits, even if we attain profitability.

We may have difficulty attracting and retaining qualified personnel and our business may suffer if we do not.

Our business has experienced a number of successes and faced several challenges in recent years that have resulted in several significant changes in our strategy and business plan, including the shifting of resources to support our current development initiatives. Our management will need to remain flexible to support our business model over the next few years. However, losing members of the Navidea team could have an adverse effect on our operations. Our success depends on our ability to attract and retain technical and management personnel with expertise and experience in the pharmaceutical industry, and the acquisition of additional product candidates may require us to acquire additional highly qualified personnel. The competition for qualified personnel in the biotechnology industry is intense and we may not be successful in hiring or retaining the requisite personnel. If we are unable to attract and retain qualified technical and management personnel, we will suffer diminished chances of future success.

~~Healthcare reform measures could hinder or prevent the commercial success of our products.~~

In March 2010, President Obama signed into law a legislative overhaul of the U.S. healthcare system, the Patient Protection and Affordable Care Act (the “PPACA”), which had far-reaching consequences for many healthcare companies, including diagnostic companies like ours. For example, if reimbursement for our products is substantially less than we or our customers expect, our business could be materially and adversely impacted. However, the future of the PPACA is uncertain and at this juncture there will be a period of uncertainty regarding the PPACA’s repeal, modification or replacement or the effect of the changes made to the PPACA under the Tax Cuts and Jobs Act of 2017, any of which could have long term financial impact on the delivery of and payment for healthcare in the United States.

Regardless of the impact of the PPACA on us, the U.S. government and other governments have shown significant interest in pursuing healthcare reform and reducing healthcare costs. Any government-adopted reform measures could cause significant pressure on the pricing of healthcare products and services in the United States and internationally, as well as the amount of reimbursement available from governmental agencies and other third-party payors.

Actual and anticipated changes to the regulations of the healthcare system and U.S. tax laws may have a negative impact on the cost of healthcare coverage and reimbursement of he~~althcare~~healthcare services and products.

The FDA and comparable agencies in other jurisdictions directly regulate many critical activities of life science, technology, and healthcare industries, including the conduct of preclinical and clinical studies, product manufacturing, advertising and promotion, product distribution, adverse event reporting, and product risk management. In both domestic and foreign markets, sales of products depend in part on the availability and amount of reimbursement by third-party payors, including governments and private health plans. Governments may regulate coverage, reimbursement, and pricing of products to control cost or affect utilization of products. Private health plans may also seek to manage cost and utilization by implementing coverage and reimbursement limitations. Substantial uncertainty exists regarding the reimbursement by third-party payors of newly approved healthcare products. The U.S. and foreign governments regularly consider reform measures that affect healthcare coverage and costs. Such reforms may include changes to the coverage and reimbursement of healthcare services and products. In particular, there have been recent judicial and Congressional challenges to the ~~PPACA,~~Patient Protection and Affordable Care Act (“PPACA”), which could have an impact on coverage and reimbursement for healthcare services covered by plans authorized by the PPACA, and we expect there will be additional challenges and amendments to the PPACA in the future.

In addition, various other healthcare reform proposals have emerged at the federal and state level. The recent changes to U.S. tax laws could also negatively impact the PPACA. We cannot predict what healthcare initiatives or tax law changes, if any, will be implemented at the federal or state level, however, government and other regulatory oversight and future regulatory and government interference with the healthcare systems could adversely impact our business.

We may not be able to maintain compliance withour internal controls and procedures.

We regularly review and update our internal controls, disclosure controls and procedures, and corporate governance policies. In addition, we are required under the Sarbanes Oxley Act of 2002 to report annually on our internal control over financial reporting. Any system of internal controls, however well designed and operated, is based in part on certain assumptions and can provide only reasonable, not absolute, assurances that the objectives of the system are met. Any failure or circumvention of the controls and procedures or failure to comply with regulation concerning control and procedures could have a material effect on our business, results of operation and financial condition. Any of these events could result in an adverse reaction in the financial marketplace due to a loss of investor confidence in the reliability of our financial statements, which ultimately could negatively affect the market price of our shares, increase the volatility of our stock price and adversely affect our ability to raise additional funding. The effect of these events could also make it more difficult for us to attract and retain qualified persons to serve on our Board of Directors and our Board committees and as executive officers.

The Company has experienced recurring net losses and has used significant cash to fund its operations, and we expect to continue to incur substantial operating losses and may be unable to obtain additional financing, causing substantial doubt about our ability to continue as a going concern over the next twelve months from the filing of this Annual Report. The report of our independent registered public accounting firm includes an explanatory paragraph that expresses substantial doubt about our ability to continue as a going concern.

Our independent registered public accounting firm’s report issued in connection with our audited financial statements for the year ended December 31, 2018 states that there is “substantial doubt about the Company’s ability to continue as a going concern.” Our ability to continue as a going concern is dependent on a combination of several factors, including, our ability to raise capital by issuing debt or equity securities to investors, license or sell our product candidates to other pharmaceutical companies, and generate revenues from successfully developed products. If we are not able to continue our business as a going concern, we may be forced to liquidate our assets for an amount less than the value at which those assets are carried on our financial statements, and it is likely that investors will lose part or all of their investment.

The Company is currently engaged in litigation with CRG and Dr. Goldberg. In addition, the Company has experienced recurring net losses and has used significant cash to fund its operations. Based on our current working capital and our projected cash burn, and without definitive agreements in place for additional funding, management believes that there is substantial doubt about the Company’s ability to continue as a going concern for at least twelve months following the issuance of this Annual Report on Form 10-K.

We currently lease approximately 5,000 square feet of office space at 4995 Bradenton Avenue, Dublin, Ohio, as our principal ~~offices. The current least term expires in June 2020,~~offices, at a monthly base rent of approximately $3,000. We must also pay a pro-rata portion of the operating expenses and real estate taxes of the building. We also lease approximately 2,000 square feet of office space at 560 Sylvan Avenue, Englewood Cliffs, New Jersey. The current lease term expires in March 2019, at a monthly base rent of approximately $3,000. We must also pay a pro-rata portion of the electricity costs of the building. We do not intend to renew the lease on the New Jersey office, nor do we currently intend to obtain alternative office space in the New York/New Jersey area.June 2023. We believe ~~both facilities are~~this facility is in good condition.

We also currently lease approximately 25,000 square feet of office space at 5600 Blazer Parkway, Dublin, Ohio, formerly our principal ~~offices.~~offices, at a monthly base rent of approximately $27,000 during 2020. The current lease term expires in October 2022 atwith an option to extend for an additional five years. The Company does not intend to renew this lease. We also sublease the space on Blazer Parkway to a monthly base rent of approximately $26,000 during 2019. We must also pay a pro-rata portion of the operating expenses and real estate taxes of the building. In June 2017, the Company executed a sublease arrangementtenant for ~~the Blazer space, providing for monthly sublease payments to Navidea of~~ approximately $39,000 ~~through~~per month, which expires in October 2022.

Item 5. Market for ~~Registrant’s~~Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities

Our ~~common stock~~Common Stock trades on the NYSE American exchange under the trading symbol “NAVB.” As of March ~~1, 2019,~~18, 2022, we had ~~approximately 590~~381 holders of ~~common stock~~Common Stock of record. There were no repurchases of our ~~common stock~~Common Stock during the year ended December 31, ~~2018.~~2021.

The following graph compares the cumulative total return on a $100 investment in each of the ~~common stock~~Common Stock of the Company, the Russell 3000, and the NASDAQ Biotechnology Index for the period from December 31, ~~2013~~2016 through December 31, ~~2018.~~2021. This graph assumes an investment in the Company’s ~~common stock~~Common Stock and the indices of $100 on December 31, ~~2013~~2016 and that any dividends were reinvested.

Among Navidea Biopharmaceuticals, the Russell 3000 Index, and the NASDAQ Biotechnology Index

* $100 invested on 12/31/2016 in stock or index, including reinvestment of dividends.

The following discussion should be read together with our Consolidated Financial Statements and the Notes related to those statements, as well as the other financial information included in this Form 10-K. Some of our discussion is forward-looking and involves risks and uncertainties. For information regarding risk factors that could have a material adverse effect on our business and future results, refer to Item 1A of this Form 10-K, ~~“Risk~~“Risk Factors.”

Navidea Biopharmaceuticals, Inc. is a biopharmaceutical company focused on the development and commercialization of precision immunodiagnostic agents and immunotherapeutics. Navidea is developing multiple precision-targeted products based on our Manocept platform to enhance patient care by identifying the sites and pathways of undetected disease and enable better diagnostic accuracy, clinical decision-making and targeted treatment.

On March 3, 2017, the Company completed the Asset Sale to Cardinal Health 414, as discussed previously under “Development of the Business.” Pursuant to the Purchase Agreement, we sold all of our assets used, held for use, or intended to be used in operating the Business, including Lymphoseek, in Canada, Mexico and the United States. Upon closing of the Asset Sale, the Supply and Distribution Agreement between Cardinal Health 414 and the Company was terminated and, as a result, the provisions thereof are of no further force or effect.

We manage our business based on two primary types of drug products: (i) diagnostic substances, including Tc99m tilmanocept and other diagnostic applications of our Manocept platform, and ~~NAV4694 (through the date of sublicensing), and~~ (ii) ~~therapeutic development programs, including~~ therapeutic applications of our Manocept ~~platform and all development programs undertaken by MT.~~platform. See Note 1815 to the consolidated financial statements for more information about our business segments.

In the near term, the Company intends to continue to develop our additional imaging product candidates into advanced clinical testing, ~~with the goal of extending~~as well as working to extend the regulatory approvals for use of the Tc99m tilmanocept product. We will also be evaluating potential funding and other resources required for continued development, regulatory approval and commercialization of any Manocept platform product candidates that we identify for further development, and potential options for advancing development.

Our operating expenses in recent years have been focused primarily on support of both diagnostic and therapeutic applications of our Manocept platform, and Tc99m ~~tilmanocept, and NAV4694 product development.~~tilmanocept. We incurred approximately ~~$4.2~~$5.1 million and ~~$4.5~~$4.9 million in total on ~~research and development~~R&D activities during the years ended December 31, ~~2018~~2021 and ~~2017,~~2020, respectively. Of the total amounts we spent on ~~research and development~~R&D during those periods, excluding costs related to our internal ~~research and development~~R&D headcount and our general and administrative staff which we do not currently allocate among the various development programs that we have underway, we incurred out-of-pocket charges by program as follows:

We expect to continue the advancement of our efforts with our Manocept platform during ~~2019. The divestiture of NAV4694 has decreased our development costs over the past year.~~2022. We currently expect our total research and development expenses, including both out-of-pocket charges as well as internal headcount and support costs, to be higher in ~~2019~~2022 than in ~~2018.~~2021. However, the ongoing global COVID-19 pandemic has impacted the global economy and may impact our operations, including the potential interruption of our clinical trial activities and our supply chain. For example, the COVID-19 outbreak delayed enrollment in our NAV3-32 clinical study in the United Kingdom due to national COVID-19-related shutdowns. In addition, the regulatory approval process in India was delayed by the impact of COVID-19 in that country. The COVID-19 pandemic may delay enrollment in our future clinical trials due to prioritization of hospital resources toward the outbreak, and some patients may be unwilling to enroll in our future trials or be unable to comply with clinical trial protocols if quarantines impede patient movement or interrupt healthcare services, which would delay our ability to conduct clinical trials or release clinical trial results. The spread of an infectious disease, including COVID-19, may also result in the inability of our suppliers to deliver clinical drug supplies on a timely basis or at all. In addition, hospitals may reduce staffing and reduce or postpone certain treatments in response to the spread of an infectious disease. Such events may result in a period of business disruption, and in reduced operations, or doctors and medical providers may be unwilling to participate in our clinical trials, any of which could materially affect our business, financial condition and results of operations.

The extent to which the ongoing global COVID-19 pandemic impacts our business will depend on future developments, which are highly uncertain and cannot be predicted, including new information that may emerge concerning the severity and spread of COVID-19, the actions taken by federal, state and local governmental authorities, both domestic and foreign, as well as private parties, to contain or treat its impact, and other events outside of our control. The COVID-19 pandemic has adversely affected economies and financial markets worldwide, resulting in an economic downturn that could impact our business, financial condition and results of operations, including our ability to obtain additional funding, if needed.

Tc99m tilmanocept is approved by the EMA for use in imaging and intraoperative detection of sentinel lymph nodes draining a primary tumor in adult patients with breast cancer, melanoma, or localized squamous cell carcinoma of the oral cavity in the EU. Following the January 2017 transfer of the Tc99m tilmanocept Marketing Authorization to SpePharm, we transferred responsibility for manufacturing the reduced-mass vial for the EU market to SpePharm. During the second quarter of 2017, SpePharm launched Tc99m tilmanocept in select EU markets, providing a number of early adopters with sample doses to provide exposure to the product. EU sales commenced during the third quarter of 2017. We anticipate that we will incur costs ~~related~~ to ~~supporting~~support our product, regulatory, manufacturing and commercial activities related to the sale of Tc99m tilmanocept in the EU, as well as related to the potential marketing registration and sale of Tc99m tilmanocept in markets other than the EU. There can be no assurance that Tc99m tilmanocept will achieve regulatory approval in any market other than the EU, or if approved in those markets, that it will achieve market acceptance in the EU or any other market. See Item 1A - “Risk Factors.”

We continue to evaluate existing and emerging data on the potential use of Manocept-related agents in the diagnosis, disease-staging and treatment of disorders in which macrophages are involved, such as RA, KS, NASH and other disease states, to define areas of focus, development pathways and partnering options to capitalize on the Manocept platform. We will also be evaluating potential funding and other resources required for continued development, regulatory approval and commercialization of any Manocept platform product candidates that we identify for further development, and potential options for advancing development. There can be no assurance of obtaining funding or other resources on terms acceptable to us, if at all, that further evaluation or development will be successful, that any Manocept platform product candidate will ultimately achieve regulatory approval, or if approved, the extent to which it will achieve market acceptance. See Item 1A - “Risk Factors.”

In March 2017, Navidea completed the Asset Sale to Cardinal Health 414, as discussed previously under “The Company.” In exchange for the Acquired Assets, Cardinal Health 414 (i) made a cash payment to the Company at closing of approximately $80.6 million after adjustments based on inventory being transferred and an advance of $3.0 million of guaranteed earnout payments as part of the CRG settlement, (ii) assumed certain liabilities of the Company associated with the Product as specified in the Purchase Agreement, and (iii) agreed to make periodic earnout payments (to consist of contingent payments and milestone payments which, if paid, will be treated as additional purchase price) to the Company based on net sales derived from the purchased Product subject, in each case, to Cardinal Health 414’s right to off-set. In no event will the sum of all earnout payments, as further described in the Purchase Agreement, exceed $230 million over a period of ten years, of which $20.1 million are guaranteed payments for the three years immediately after closing of the Asset Sale. At the closing of the Asset Sale, $3.0 million of such earnout payments were advanced by Cardinal Health 414 to the Company, and paid to CRG.

In April 2018, the Company entered into an Amendment to the Asset Purchase Agreement. Pursuant to the Amendment, Cardinal Health 414 paid the Company approximately $6.0 million and agreed to pay the Company an amount equal to the unused portion of the letter of credit (not to exceed approximately $7.1 million) promptly after the earlier of (i) the expiration of the letter of credit and (ii) the receipt by Cardinal Health 414 of evidence of the return and cancellation of the letter of credit. In exchange, the obligation of Cardinal Health 414 to make any further contingent payments has been eliminated. Cardinal Health 414 is still obligated to make the milestone payments in accordance with the terms of the earnout provisions of the Purchase Agreement. CRG has drawn the entire $7.1 million available under the letter of credit.

We recorded a net gain on the sale of the Business of $89.2 million for the year ended December 31, 2017, including $16.5 million in guaranteed consideration, which was discounted to the present value of future cash flows. The proceeds were offset by $3.3 million in estimated fair value of warrants issued to Cardinal Health 414, $2.0 million in legal and other fees related to the sale, $800,000 in net balance sheet dispositions and write-offs, and $4.1 million in estimated taxes. We recorded an additional gain related to the Amendment to the Asset Purchase Agreement of $43,000 for the year ended December 31, 2018, including $54,000 of additional consideration, offset by $11,000 in estimated taxes.

Our consolidated balance sheets and statements of operations have been reclassified, as required, for all periods presented to reflect the Business as a discontinued operation. Cash flows associated with the operation of the Business have been combined with operating, investing and financing cash flows, as appropriate, in our consolidated statements of cash flows.

This discussion of our Results of Operations focuses on describing results of our operations as if we had not operated the discontinued operations discussed above during the periods being disclosed. In addition, since our remainingOur pharmaceutical products and product candidates are not yet generating significant commercial revenue, therefore the discussion of our revenue focuses on the grant and other revenue and our operating variances focus on our ~~remaining~~ product development programs and the supporting general and administrative expenses.

Royalty Revenue. During ~~2018 and 2017,~~2020, we recognized royalty revenue of ~~$15,000 and $9,000, respectively,~~$8,000 related to our license agreement with SpePharm in Europe. No royalty revenue was recorded during 2021. The decrease in royalty revenue was due to termination of our license agreement with SpePharm in May 2020.

License Revenue. During ~~2018,~~2021 and 2020, we recognized license revenue of ~~$307,000, primarily for a non-refundable upfront payment~~$46,000 and $111,000, respectively, related to net transitional sales from SpePharm in Europe. The decrease in license revenue was due to the ~~sublicense~~cessation of ~~NAV4694 to Meilleur and the sublicense~~active marketing of Tc99m tilmanocept ~~to Sinotau~~ in ~~China. During 2017, we recognized~~Europe following the termination of our license ~~revenue of $100,000 for a non-refundable upfront payment related to the Tc99m tilmanocept license and distribution~~ agreement with ~~Sayre Therapeutics~~SpePharm in ~~India.~~May 2020.

Grant and Other Revenue. During ~~2018,~~2021, we recognized ~~$847,000~~$486,000 of grant and other revenue compared to ~~$1.7 million~~$796,000 in ~~2017.~~2020. Grant revenue of $88,000 and $696,000 during ~~2018~~2021 and 2020, respectively, was primarily related to SBIR grants from the NIH supporting Manocept development. ~~Grant~~Other revenue during ~~2017 was primarily related to SBIR grants~~2021 included $298,000 from LikeMinds for the ~~NIH supporting Manocept, therapeutic~~partial recovery of debts previously written off in 2015 and ~~Tc99m tilmanocept development.~~$100,000 from Cardinal Health 414 for reimbursement of certain research and development costs. Other revenue for ~~2018 and 2017~~2020 included ~~$85,000 and $31,000, respectively,~~$100,000 from Alseres for the partial recovery of ~~revenue primarily from our marketing partners~~debts previously written off in ~~Europe and China related to development work performed at their request.~~2015.

Research and Development Expenses. ~~Research and development~~R&D expenses ~~decreased $292,000,~~increased $212,000, or 6%4%, to ~~$4.2~~$5.1 million during ~~2018~~2021 from ~~$4.5~~$4.9 million during ~~2017.~~2020. The ~~decrease~~increase was primarily due to increased regulatory consulting expenses of $101,000, increased employee compensation including incentive-based awards of $82,000, increased travel costs of $30,000, increased recruiting fees of $28,000 and increased general office expenses of $19,000. These increases were coupled with net ~~decreases~~increases in drug project expenses related to (i) ~~decreased Manocept~~increased therapeutics development costs of ~~$849,000, primarily decreased~~$316,000, including increased preclinical and clinical ~~trial~~development costs; and (ii) ~~decreased~~increased Tc99m tilmanocept development costs of ~~$91,000~~$79,000, primarily European regulatory consulting expenses; offset by (iii) decreased Manocept diagnostic development costs of $388,000 including decreased license fees and manufacturing-related activities ~~and clinical testing,~~ offset by increased ~~regulatory costs; offset by (iii) increased NAV4694 development costs of $391,000 due to reversal of certain previously accrued expenses during 2017, offset by decreased~~ clinical testing; (iv) increased therapeutics development costs of $350,000, including increased research consulting, regulatory consulting, and preclinical testing, offset by decreased manufacturing-related activities; and (v) increased NAV5001 development costs of $91,000 due to reversal of certain previously accrued expenses during 2017 . The net decrease in research and development expenses also included decreased compensation including incentive-based awards of $309,000 related to net decreased headcount offset by increased general office and travel expenses totaling $124,000.trial costs.

Selling, General and Administrative Expenses. Selling, general and administrative expenses ~~decreased $3.5 million,~~increased $755,000, or ~~31%~~11%, to ~~$7.7~~$7.5 million during ~~2018~~2021 from ~~$11.2~~$6.7 million during ~~2017.~~2020. The net ~~decrease~~increase was primarily due to separation expenses of $969,000 related to the resignation of our former Chief Executive Officer, increased consulting services of $413,000 related to European distribution of Tc99m tilmanocept, increased director fees of $189,000 related to additional board members and increased board compensation rates, increased insurance costs of $176,000, losses on the abandonment of certain intellectual property of $93,000, recruiting fees of $75,000 related to our search for a new Chief Executive Officer, increased travel expenses of $52,000 and increased general office expenses of $34,000 primarily related to technology upgrades, offset by decreased legal and professional services of $2.7 million primarily related to the CRG litigation, a loss on disposal of assets related to our previous office space of $706,000 and a loss on termination of our previous office lease of $399,000, both during 2017,$580,000, and decreased ~~general office, insurance, depreciation, rent,~~employee compensation including incentive-based awards of $471,000, decreased investor relations costs of $133,000, decreased EMA and ~~travel expenses totaling $388,000. The net decrease in selling, general~~other annual registration fees of $30,000, decreased facilities costs of $27,000 and ~~administrative expenses also included net increased compensation expense~~decreased franchise taxes of ~~$668,000, including termination costs related to the resignation of Dr. Goldberg of $1.1 million in 2018 and termination costs related to the arbitration award to Mr. Gonzalez of $478,000 in 2017.~~$13,000.

Other Income (Expense). Other ~~expense,~~income, net, was ~~$5.3 million~~$346,000 during ~~2018~~2021 compared to other expense, net, of ~~$3.9 million~~$11,000 during ~~2017. We recorded losses~~2020. During 2021, we recognized a gain on extinguishment of ~~the CRG~~ debt of ~~$5.3 million~~$366,000 resulting from forgiveness of our PPP loan. During 2021 and ~~$4.2 million during 2018 and 2017, respectively. Also during 2018 and 2017,~~2020, we recognized interest income of ~~$131,000~~$3,000 and ~~$328,000, respectively, primarily related to the guaranteed consideration due from Cardinal Health 414, which was discounted to present value at the closing date of the Asset Sale in 2017.~~$18,000, respectively. During ~~2018~~2021 and ~~2017, $153,000 and $265,000, respectively, of~~2020, we recorded interest expense ~~was compounded~~of $9,000 and ~~added to the balance of our note payable to Platinum. During 2017, we recorded non-cash income of $153,000 related to changes in the estimated fair value of financial instruments.~~

~~Gain on~~ ~~Discontinued Operations.~~ We recorded a net gain related to the Amendment to the sale of the Business to Cardinal Health 414 of $43,000 in 2018, including $54,000 of payments by Cardinal Health 414 to Navidea in excess of receivables recognized, offset by $11,000 in estimated taxes. We recorded a net gain on the sale of the Business to Cardinal Health 414 of $89.2 million in 2017, including $16.5 million in guaranteed consideration, which was discounted to the present value of future cash flows. The proceeds were offset by $3.3 million in estimated fair value of warrants issued to Cardinal Health 414, $2.0 million in legal and other fees related to the sale, $800,000 in net balance sheet dispositions and write-offs, and $4.1 million in estimated taxes. Operating income (loss) from discontinued operations related to the sale of the Business to Cardinal Health 414 were $1,000 and ($491,000) for 2018 and 2017,$7,000, respectively.

Cash balances increased ~~$681,000~~ to ~~$3.5~~$4.2 million atas of December 31, ~~2018~~2021 from ~~$2.8~~$2.7 million atas of December 31, ~~2017.~~2020. The net increase was primarily due to ~~accelerated receipt of the guaranteed earnout receivable from Cardinal Health 414 of $5.7 million,~~ net ~~of CRG’s draw on the letter of credit of $7.2 million,~~ proceeds from ~~a private equity placement~~issuance of ~~$3.0 million, and maturities and sales~~preferred stock of ~~available-for-sale securities of $1.6~~$12.6 million, offset by cash used to fund our operations of ~~$1.5 million.~~$10.2 million, payments on notes payable of $492,000 and patent and trademark costs of $304,000.

Operating Activities. Cash ~~provided by~~used in operations was ~~$4.3~~$10.2 million during ~~2018~~2021 compared to ~~$59.1~~$8.2 million cash used in operations during ~~2017.~~2020.

~~Accounts~~Stock subscriptions and other receivables decreased ~~$8.1~~$2.9 million to ~~$21,000 at~~$93,000 as of December 31, ~~2018~~2021 from ~~$8.1~~$3.0 million atas of December 31, ~~2017,~~2020, primarily due to decreased preferred stock subscriptions of $2.9 million and decreased amounts receivable for transitional sales revenue from SpePharm of $58,000, offset by increased amounts receivable from related ~~to Cardinal Health 414’s payment~~parties for reimbursement of ~~the entire balance~~legal fees of ~~the guaranteed earnout of $12.9 million pursuant to the Amendment executed on April 2, 2018.~~$90,000.

Inventory decreased $19,000 to $151,000 as of December 31, 2021 from $170,000 as of December 31, 2020, primarily due to materials allocated to manufacturing process development of $28,000 offset by increased finished goods inventory of $13,000 due to finished goods cost adjustments.

Prepaid expenses and other current assets increased ~~$198,000~~$207,000 to ~~$1.3 million at~~$908,000 as of December 31, ~~2018~~2021 from ~~$1.1 million at~~$701,000 as of December 31, ~~2017.~~2020. The increase was primarily due to a net increase in ~~federal~~prepaid insurance of $160,000, an upfront contract payment of $56,000 related to a clinical study and ~~state tax refunds receivable,~~an upfront contract payment of $23,000 related to manufacturing process development, offset by the return of a ~~net decrease in prepaid insurance and decreased interest receivable related to the guaranteed earnout due from Cardinal Health 414.~~retainer for legal services of $30,000.

Accounts payable ~~decreased $430,000~~increased $260,000 to ~~$425,000 at~~$1.4 million as of December 31, ~~2018~~2021 from ~~$855,000 at~~$1.2 million as of December 31, ~~2017,~~2020, primarily driven by net increased payables due for Manocept development costs, manufacturing-related activities, therapeutics development costs and investor relations costs, offset by net decreased payables due ~~to operations, NAV4694~~for Navidea Europe costs and ~~therapeutics vendors, offset by increased payables due to Manocept development vendors.~~legal and professional services. Accrued liabilities and other current liabilities increased ~~$663,000~~$636,000 to $3.1 million as of December 31, 2021 from $2.5 million atas of December 31, ~~2018 from $1.9 million at December 31, 2017.~~2020. Increased accruals ~~for termination~~related to the separation of ~~Dr. Goldberg and~~our former Chief Executive Officer, Manocept development ~~vendors~~costs, employee benefits and Navidea Europe were offset by ~~decreases in~~decreased accruals for incentive-based compensation and legal and professional services. Our payable and accrual balances will continue to fluctuate, ~~but will likely decrease overall as we work to resolve our legal disputes, offset by~~with planned increases in development activity related to the Manocept ~~platform.~~platform offset by decreased legal fees as we continue to work to resolve our legal disputes.

Investing Activities. Investing activities ~~provided $954,000~~used $329,000 during ~~2018~~2021 compared to ~~$1.8 million~~$413,000 used during ~~2017. Investing activities during 2018 included maturities~~2020. Patent and ~~sales of available-for-sale securities of $1.6 million,~~trademark costs used $304,000 and purchases of ~~available-for-sale securities of $600,000,~~property and ~~capital expenditures of $46,000, primarily for research~~equipment used $25,000 during 2021. Patent and ~~computer equipment. Investing activities during 2017 included~~trademark costs used $278,000 and purchases of ~~available-for-sale securities of $2.2 million~~property and ~~capital expenditures of $34,000, primarily for computer~~ equipment and leasehold improvements, offset by maturities of available-for-sale securities of $400,000. We expect our overall capital expenditures for 2019 will be higher than 2018 as we work to increase our manufacturing efficiency and maintain our technology infrastructure.used $136,000 during 2020.

Financing Activities. Financing activities ~~used $4.5~~provided $12.1 million during ~~2018~~2021 compared to ~~$61.0~~$10.2 million provided during ~~2017.~~2020. The ~~$4.5~~$12.1 million ~~used~~provided by financing activities ~~during 2018~~in 2021 consisted primarily of ~~CRG’s draw on the letter~~proceeds from issuance of ~~credit~~preferred stock of ~~$7.1~~$12.7 million, ~~and~~offset by principal payments on financed insurance premiums of ~~$396,000, offset by proceeds from a private equity placement~~$492,000, payment of ~~$3.0 million.~~preferred stock issuance costs of $70,000 and payment of tax withholdings related to stock-based compensation of $17,000. The ~~$61.0~~$10.2 million ~~used~~provided by financing activities ~~in 2017~~during 2020 consisted primarily of proceeds from the issuance of preferred stock of $6.0 million, proceeds from the issuance of Common Stock of $4.4 million, and proceeds from notes payable of $366,000, offset by principal payments on ~~the CRG, Platinum and IPFS notes payable~~financed insurance premiums of ~~$59.8 million~~$369,000, payment of Common Stock issuance costs of $150,000 and payment of ~~debt-related~~preferred stock issuance costs of ~~$1.3 million, offset by proceeds from issuance of common stock of $72,000.~~$55,000.

OnThe Coronavirus Aid, Relief, and Economic Security Act (the “CARES Act”) was enacted on March ~~3, 2017, pursuant to a Purchase Agreement dated November 23, 2016,~~27, 2020. Among the ~~Company completed its previously announced sale to Cardinal Health 414~~provisions contained in the CARES Act was the creation of ~~its assets used, held~~the Payroll Protection Program (“PPP”) that provides for ~~use, or intended~~Small Business Administration (“SBA”) Section 7(a) loans for qualified small businesses. PPP loan proceeds are available to be used ~~in operating the Business,~~to pay for payroll costs, including ~~the Product, in the Territory (giving effect to the License-Back~~salaries, commissions, and excluding certain assets specifically retained by the Company). Such assets sold in the Asset Sale consist primarily of, without limitation, (i) intellectual property used in or reasonably necessary for the conduct of the Business, (ii) inventory of,similar compensation, group health care benefits, and customer, distribution, and product manufacturing agreements related to, the Business, (iii) all product registrations related to the Product, including the new drug application approved by the FDA for the Product and all regulatory submissions in the United States that have been made with respect to the Product and all Health Canada regulatory submissions and, in each case, all files and records related thereto, (iv) all related clinical trials and clinical trial authorizations and all files and records related thereto, and (v) all right, titlepaid leaves; rent; utilities; and interest ~~in and to the Product, as specified in the Purchase Agreement. Upon closing of the Asset Sale, the Supply and Distribution Agreement between Cardinal Health 414 and the Company was terminated and, as~~on certain other outstanding debt. On May 18, 2020, Fifth Third Bank (the “Lender”) funded a ~~result, the provisions thereof are of no further force or effect.~~

~~In exchange for the Acquired Assets, Cardinal Health 414 (i) made a cash payment~~PPP loan to the Company at closing of approximately $80.6 million after adjustments based on inventory being transferred and an advance of $3.0 million of guaranteed earnout payments as part of the CRG settlement, (ii) assumed certain liabilities of the Company associated with the Product as specified in the ~~Purchase Agreement, and (iii) agreed to make periodic earnout payments (to consist~~amount of contingent payments and milestone payments which, if paid, will be treated as additional purchase price) to the Company based on net sales derived from the purchased Product subject, in each case, to Cardinal Health 414’s right to off-set.$366,000 (the “PPP Loan”). In no event will the sum of all earnout payments, as further described in the Purchase Agreement, exceed $230 million over a period of ten years, of which $20.1 million are guaranteed payments for the three years immediately after closing of the Asset Sale. At the closing of the Asset Sale, $3.0 million of such earnout payments were advanced by Cardinal Health 414 to the Company, and paid to CRG.

We recorded a net gain on the sale of the Business of $89.2 million for the year ended December 31, 2017, including $16.5 in guaranteed consideration, which was discounted to the present value of future cash flows. The proceeds were offset by $3.3 million in estimated fair value of warrants issued to Cardinal Health 414, $2.0 million in legal and other fees related to the sale, $800,000 in net balance sheet dispositions and write-offs, and $4.1 million in estimated taxes. The guaranteed consideration was recorded as a receivable, the balance of which was being reduced as quarterly payments were received.

On April 2, 2018, the Company entered into an Amendment to the Asset Purchase Agreement. Pursuant to the Amendment, Cardinal Health 414 paid the Company approximately $6.0 million and agreed to pay the Company an amount equal to the unused portion of the letter of credit (not to exceed approximately $7.1 million) promptly after the earlier of (i) the expiration of the letter of credit and (ii) the receipt by Cardinal Health 414 of evidence of the return and cancellation of the letter of credit. In exchange, the obligation of Cardinal Health 414 to make any further contingent payments has been eliminated. Cardinal Health 414 is still obligated to make the milestone payments in accordance with the ~~terms~~loan forgiveness requirements of the ~~earnout provisions~~CARES Act, the Company used the proceeds from the PPP Loan primarily for payroll costs, rent and utilities. On February 23, 2021, the Lender notified the Company that the entire PPP Loan amount of the Purchase Agreement. We recorded an additional gain related to the Amendment to the Asset Purchase Agreement of $43,000 for the year ended December 31, 2018, including $54,000 of additional consideration, offset by $11,000 in estimated taxes. On April 9, 2018, CRG drew approximately $7.1 million on the letter of credit.$366,000 had been forgiven. See ~~Note 3~~Notes 2 and 10 to the accompanying consolidated financial statements.

On February 14, 2020, we executed an agreement with an investor to purchase approximately 1.6 million shares of our Common Stock at a price of $0.85 per share for aggregate gross proceeds to Navidea of $1.4 million. The offering was made pursuant to our shelf registration statement on Form S‑3 (Registration No. 333-222092), which was declared effective by the SEC on December 27, 2017, including the prospectus contained therein, as well as a prospectus supplement filed with the SEC on February 18, 2020. See Notes 2 and 13 to the accompanying consolidated financial statements.

On February 13, 2020, we executed a stock purchase agreement with John K. Scott, Jr. to purchase approximately 2.4 million shares of Common Stock for aggregate gross proceeds of approximately $2.0 million. A registration statement on Form S-3 (Registration No. 333-248404) covering the resale of the shares of Common Stock issued to Mr. Scott was declared effective by the SEC on September 16, 2020. See Notes 2 and 13 ~~2018,~~to the accompanying consolidated financial statements.

On August 30, 2020, the Company entered into a Common Stock Purchase Agreement with the Investors named therein, pursuant to which the Investors agreed to purchase from the Company up to $25.0 million in shares of the Company’s Common Stock. To date, we have received only $25,000 of the $5.0 million that was owed under the Common Stock Purchase Agreement. We are continuing to evaluate our rights and remedies under that agreement. Effective December 14, 2021, Navidea terminated the Common Stock Purchase Agreement. See Notes 2 and 13 to the accompanying consolidated financial statements.

On May 6, 2020, the Company entered into a Stock Purchase Agreement and Letter of Investment Intent with Keystone Capital Partners, LLC (“Keystone”) pursuant to which the Company agreed to issue to Keystone 420,000 shares of newly-designated Series C Redeemable Convertible Preferred Stock (the “Series C Preferred Stock”) for an aggregate purchase price of $4.2 million. All $4.2 million were received and the related Series C Preferred Stock was issued during the second and third quarters of 2020. The 420,000 shares of Series C Preferred Stock were subsequently converted into 1,425,076 shares of Common Stock. See Notes 2 and 14 to the accompanying consolidated financial statements.

On August 31, 2020, the Company entered into a Stock Purchase Agreement and Letter of Investment Intent (the “Series D Preferred Stock Purchase Agreement”) with Keystone pursuant to which the Company agreed to issue to Keystone 150,000 shares of newly-designated Series D Redeemable Convertible Preferred Stock (the “Series D Preferred Stock”) for an aggregate purchase price of $15.0 million. Pursuant to the Series D Preferred Stock Purchase Agreement, Keystone agreed to purchase Series D Preferred Stock in amounts to be determined by Keystone in one or more closings before the end of the nine-month period following the date when the Company’s prospectus supplement to its existing registration statement on Form S-3 was filed with the SEC. Through July 7, 2021, Keystone purchased 72,500 shares of Series D Preferred Stock pursuant to the Series D Preferred Stock Purchase Agreement for an aggregate purchase price of $7.25 million, leaving a remaining balance of 77,500 shares of Series D Preferred Stock. On July 8, 2021 (the “Amendment Effective Date”), the Company entered into an Amendment to Stock Purchase Agreement and Letter of Investment Intent (the “Series D Amendment”) with Keystone pursuant to which Keystone purchased 22,077 shares of Series D Preferred Stock for an aggregate purchase price of approximately $2.2 million. After purchasing the 22,077 shares, Keystone has no further right or obligation to purchase shares of Series D Preferred Stock. Including the purchases pursuant to the Series D Amendment, Keystone’s purchases of Series D Preferred Stock pursuant to the Series D Purchase Agreement during the year ended December 31, 2021 totaled 76,827 shares of Series D Preferred Stock for an aggregate purchase price of approximately $7.7 million. The Series D Preferred Stock is convertible into a maximum of 5,147,000 shares of Common Stock. See Notes 2 and 13 to the accompanying consolidated financial statements.

On March 2, 2021, the Company entered into a Stock Purchase Agreement and Letter of Investment Intent with an existing accredited investor, John K. Scott, Jr., pursuant to which the Company issued to Mr. Scott in a private placement transaction 50,000 shares of newly-designated Series E Redeemable Convertible Preferred Stock (the “Series E Preferred Stock”) for an aggregate purchase price of $5.0 million. On January 31, 2022, pursuant to the Certificate of Designations of the Series E Redeemable Convertible Preferred Stock dated March 2, 2021, the holder of the Series E Preferred Stock, John K. Scott, Jr., notified the Company that he was exercising his option to extend the Conversion Deadline (as defined therein) for an additional period of six months. The Series E Preferred Stock is convertible into a maximum of 2,173,913 shares of Common Stock. See Notes 2 and 13 to the accompanying consolidated financial statements.

On August 9, 2020, the Company entered into a binding memorandum of understanding (“MOU”) with Jubilant Draximage Inc., dba Jubilant Radiopharma, Radiopharmaceuticals Division (“Jubilant”). The MOU outlines the terms and framework for a potential Exclusive License and Distribution Agreement (“ELDA”) for Navidea’s Tc99m-Tilmanocept Rheumatoid Arthritis diagnostic application in the United States, Canada, Mexico, and Latin America. In connection with the MOU, the Company entered into a Stock Purchase Agreement with ~~an investor,~~Jubilant, pursuant to which ~~the Company issued 18,320,610~~Jubilant purchased $1.0 million in shares of the Company’s ~~common stock~~Common Stock in exchange for ~~$3.0 million~~exclusivity of negotiations while due diligence efforts are completed.

The execution of the ELDA is subject to certain conditions, including negotiation of a definitive agreement in ~~cash. The Company plans to use the proceeds from the Private Placement for general working capital purposes, including, without limitation, research~~mutually acceptable form and ~~development, and other operating expenses.~~Jubilant’s completion of its due diligence. See Notes 2 and ~~16(a)~~13 to the accompanying consolidated financial statements.

Latkin Separation Agreement. On November 23, 2021, Jed A. Latkin signed a Separation Agreement and General Release (the “Separation Agreement”) in connection with his resignation from his positions as Chief Executive Officer, Chief Operating Officer and Chief Financial Officer, and as a director, on October 24, 2021 (the “Separation Date”). Pursuant to the Separation Agreement, among other things, the Company agreed to the continued payment of Mr. Latkin’s base salary of $490,000, less all relevant taxes and other withholdings, on the following basis: (i) for 12 months, 100% of his base salary, minus an aggregate $24,000 deducted monthly pro rata for reimbursement of Mr. Latkin’s attorney fees which were paid by the Company, and (ii) for 10 months following the expiration of the first 12-month period, 50% of his base salary. As of December 31, 2021, there were approximately $633,000 of payments remaining under the Separation Agreement.

Financed Insurance Premiums. In November 2021, the Company prepaid $566,000 of insurance premiums through the issuance of a note payable to IPFS Corporation with an interest rate of 4.36%. The note is payable in five monthly installments of approximately $114,000, with the final payment due in April 2022. As of December 31, 2021, there were approximately $458,000 of payments remaining on the note.

Clinical Research Agreements. We have agreements in place with multiple clinical trial sites for conduct of our clinical studies, as well as with several contract research organizations for clinical trial-related services such as image and data management, monitoring, and statistical services. As of December 31, 2021, there were approximately $496,000 of payments currently due related to clinical research agreements.

UCSD License Agreements. Under our license agreements with UCSD, we have exclusive world-wide rights to all diagnostic and therapeutic uses of tilmanocept, other than Tc99m tilmanocept used in lymphatic mapping in the United States, Canada and Mexico which rights are licensed to Cardinal Health. The UCSD license agreements include obligations for payments related to license fees, milestones, and royalties. As of December 31, 2021, the Company has accrued approximately $1.6 million of payments related to the UCSD license agreements for which we have not yet been invoiced.

See Notes 2 and 12 to the accompanying condensed consolidated financial statements.

Our future liquidity and capital requirements will depend on a number of factors, including the ability of our distribution partners to achieve market acceptance of our products, our ability to complete the development and commercialization of new products, our ability to ~~monetize our investment in non-core technologies, our ability to~~ obtain milestone or development funds from potential development and distribution partners, regulatory actions by the FDA and international regulatory bodies, the ability to procure required financial resources, the outcome of any pending litigation, and intellectual property protection.

We plan to focus our resources ~~in 2019 primarily~~during 2022 on development of products based on the Manocept platform. Although management believes that it will be able to achieve this objective, it is subject to a number of variables beyond our control, including the nature and timing of any partnering opportunities, the ability to modify contractual commitments made in connection with these programs, and the timing and expense associated with suspension or alteration of clinical trials, and consequently ~~there can be no assurance that we will be able to achieve our objective of bringing our expenses in line with our revenues, and~~ we may need to seek additional financing ~~if we cannot achieve that objective~~ in ~~a timely manner.~~order to support our planned development programs.

We will continue to evaluate our ~~time lines,~~timelines, strategic needs, and balance sheet requirements. If we attempt to raise additional capital through debt, royalty, equity or otherwise, we may not be successful in doing so on terms acceptable to the Company, if at all. Although on February 14, 2022 we filed a registration statement with the Securities and Exchange Commission to register the sale of up to $35 million of Company Common Stock pursuant to a rights offering, the terms and timing of such rights offering have not yet been determined by the Company and there is no assurance that such rights offering will occur Further, we may not be able to gain access and/or be able to secure new sources of funding, identify new development opportunities, successfully obtain regulatory approval for and commercialize new products, achieve significant product revenues from our products, or achieve or sustain profitability in the future.

The Company is currently engaged in litigation with ~~CRG~~Dr. Goldberg and ~~Dr. Goldberg.~~ CRG. While the Company believes that the ultimate resolution of these matters will not have a material impact on the Company's financial statements, the outcome of litigation is inherently uncertain and the final resolution of these matters may result in expense to the Company in excess of management's expectations.

In addition, the Company has experienced recurring net losses and has used significant cash to fund its operations. The COVID-19 pandemic may negatively impact the Company’s operations, including possible effects on its financial condition, ability to access the capital markets on attractive terms or at all, liquidity, operations, suppliers, industry, and workforce. We do not believe there has been a significant impact to the Company’s clinical development and regulatory timelines resulting from the ongoing COVID-19 global pandemic. However, the COVID-19 outbreak delayed enrollment in our NAV3-32 clinical study in the United Kingdom due to national COVID-19-related shutdowns. In addition, the regulatory approval process in India has been delayed by the impact of COVID-19 in that country. The COVID-19 pandemic has adversely affected economies and financial markets worldwide, resulting in an economic downturn that could impact our business, financial condition and results of operations, including our ability to obtain additional funding, if needed. The Company will continue to evaluate the impact that the COVID-19 pandemic could have on the operations, financial position, and the results of operations and cash flows during fiscal year 2022 and beyond.

The Company has experienced recurring net losses and has used significant cash to fund its operations. The Company has considerable discretion over the extent of development project expenditures and ~~have~~has the ability to curtail the related cash flows as needed. The Company also has funds remaining under outstanding grant awards, and continues working to establish new sources of funding, including collaborations, potential equity investments, and additional grant funding that can augment the balance sheet. However, based on our current working capital and our projected cash burn, ~~and without definitive agreements in place for additional funding,~~ management believes that there is substantial doubt about the Company’s ability to continue as a going concern for ~~at least twelve months following~~a period of one year from the ~~issuance~~filing of this Annual Report on Form 10-K. No adjustments have been made to the accompanying condensed consolidated financial statements as a result of this uncertainty. See Note 2 to the accompanying consolidated financial statements and Item 1A – “Risk Factors.”

See Notes ~~1(q)~~1(m) and ~~1(r)~~1(o) to the accompanying consolidated financial statements.

Revenue Recognition. We currently generate revenue ~~primarily~~ from ~~grants~~a grant to support ~~various~~a product development ~~initiatives.~~initiative. We generally recognize grant revenue when expenses reimbursable under the ~~grants~~grant have been paid and payments under the ~~grants~~grant become contractually due.

Research and Development. R&D expenses include both internal R&D activities and external contracted services. Internal R&D activity expenses include salaries, benefits, and stock-based compensation, as well as travel, supplies, and other costs to support our R&D staff. External contracted services include clinical trial activities, chemistry, manufacturing and control-related activities, and regulatory costs. R&D expenses are charged to operations as incurred. We review and accrue R&D expenses based on services performed and rely upon estimates of those costs applicable to the stage of completion of each project.

Series C, Series D and Series E Convertible Preferred Stock. The Company evaluated the provisions of the Series C, Series D and Series E Preferred Stock under Accounting Standards Codification (“ASC”) 480, Distinguishing Liabilities from Equity, ASC 815, Derivatives and Hedging, ASC 470, Debt, and Accounting Series Release (“ASR”) 268, Presentation in Financial Statements of “Redeemable Preferred Stocks.” Based on this evaluation, the Company determined that the Series C, Series D and Series E Preferred Stock are not mandatorily redeemable financial instruments and any obligation to issue a variable number of shares of Common Stock is not unconditional. Accordingly, the Series C, Series D and Series E Preferred Stock should be classified as equity. Neither the embedded conversion option nor the embedded call option meet the criteria to be separated from the Series C, Series D or Series E Preferred stock and thus these features should not be bifurcated and accounted for as derivatives. Additionally, the Series C and Series D Preferred Stock contain a beneficial conversion feature (“BCF”). Prior to the January 1, 2021 adoption of Accounting Standards Update (“ASU”) No. 2020-06, Accounting for Convertible Instruments and Contracts in an Entity’s Own Equity, the BCF resulted in an increase to additional paid-in capital and a discount on the Series C and Series D Preferred Stock. The discounts on the Series C and Series D Preferred Stock were considered to be fully amortized at the date of issuance because the Series C and Series D Preferred Stock are immediately convertible, resulting in a deemed dividend at the date of issuance for the amount of the BCF. Following adoption of ASU 2020-06, no BCF is recorded in the consolidated financial statements. Finally, the Company determined that the conversion features of the Series C Preferred Stock could result in the Company being required to redeem a portion of the shares converted, thus the Series C Preferred Stock should be classified in mezzanine equity. Conversely, the Company determined that the Series D and Series E Preferred Stock do not contain conversion features that could result in the Company being required to redeem a portion of the shares converted, thus the Series D and Series E Preferred Stock should not be classified in mezzanine equity.

Use of Estimates. The preparation of financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and disclosures of contingent assets and liabilities at the date of the financial statements and the reported amounts of revenues and expenses during the reporting period. We base these estimates and assumptions upon historical experience and existing, known circumstances. Actual results could differ from those estimates. ~~Specifically, management may make significant estimates in the following areas:~~

We estimate the expected term based on the contractual term of the awards and employees' exercise and expected post-vesting termination behavior. Restricted stock awards are valued based on the closing stock price on the date of grant and amortized ratably over the estimated life of the award.

Since stock-based compensation is recognized only for those awards that are ultimately expected to vest, we have applied an estimated forfeiture rate to unvested awards for the purpose of calculating compensation cost. These estimates will be revised, if necessary, in future periods if actual forfeitures differ from estimates. Changes in forfeiture estimates impact compensation cost in the period in which the change in estimate occurs.

Our consolidated financial statements, and the related notes, together with the report of Marcum LLP dated March ~~15, 2019,~~28, 2022, are set forth at pages F-1 through ~~F-36~~F-32 attached hereto and incorporated herein by reference.

Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure

We maintain disclosure controls and procedures designed to ensure that information required to be disclosed in reports filed under the Exchange Act is recorded, processed, summarized, and reported within the specified time periods. As a part of these controls, our management is responsible for establishing and maintaining adequate internal control over financial reporting, as such term is defined in Rule 13a-15(f) under the Exchange Act.

Under the supervision and with the participation of our management, including ~~Mr. Latkin, who serves as~~our Executive Leadership Committee which consists of our Chief ~~Executive~~Medical Officer, ~~Chief Operating Officer~~Vice President of Operations and ~~Chief Financial Officer,~~Vice President of Finance and Administration, we evaluated the effectiveness of the design and operation of our disclosure controls and procedures (as defined in Rule 13a-15(e) under the Exchange Act) as of December 31, ~~2018,~~2021, and concluded that our disclosure controls and procedures were effective as of the end of the period covered by this report to ensure that information required to be disclosed by us in the reports that we file or submit is recorded, processed, summarized and reported within the time periods specified in the SEC’s rules and forms. Disclosure controls and procedures include, without limitation, controls and procedures designed to ensure that information required to be disclosed by us in the reports that we file or submit under the Exchange Act is accumulated and communicated to our management, including our principal executive and principal financial officers, as appropriate to allow timely decisions regarding required disclosure.

Our management ~~including Mr. Latkin, who serves as our Chief Executive Officer, Chief Operating Officer and Chief Financial Officer,~~ understands that our disclosure controls and procedures do not guarantee that all errors and all improper conduct will be prevented. A control system, no matter how well conceived and operated, can provide only reasonable, not absolute, assurance that the objectives of the control system are met. Further, a design of a control system must reflect the fact that there are resource constraints, and the benefit of controls must be considered relative to their costs. Because of the inherent limitations in all control systems, no evaluation of controls can provide absolute assurance that all control issues and instances of improper conduct, if any, have been detected. These inherent limitations include the realities that judgments and 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 persons, or by management override of the control. Further, the design of any system of controls is also based in part upon 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 the degree of compliance with the policies or procedures may deteriorate. Because of the inherent limitations of a cost-effective control system, misstatements due to error or fraud may occur and may not be detected.

~~Management’s~~Management’s Report on Internal Control Over Financial Reporting

Our management is responsible for establishing and maintaining adequate internal control over financial reporting. Our internal control system was designed to provide reasonable assurance to management and the Board of Directors regarding the preparation and fair presentation of published financial statements. All internal control systems, no matter how well designed, have inherent limitations. Therefore, even those systems determined to be effective can provide only reasonable assurance with respect to financial statement preparation and presentation.

Our 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 generally accepted accounting principles, and includes those policies and procedures that:

Under the supervision and with the participation of our management, ~~including Mr. Latkin, who serves as our Chief Executive Officer, Chief Operating Officer and Chief Financial Officer,~~ we conducted an evaluation of the effectiveness of our internal control over financial reporting as of December 31, ~~2018~~2021 based upon the criteria set forth in Internal Control – Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission (“COSO”). Based on our assessment we concluded that, as of December 31, ~~2018,~~2021, our internal control over financial reporting was effective based on those criteria.

During the year ended December 31, ~~2018,~~2021, there were no changes in our internal control over financial reporting that materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

Set forth below are the names and committee assignments of the persons who constitute our Board of Directors.

The Board of Directors believes that individuals who serve on the Board should have demonstrated notable or significant achievements in their respective field; should possess the requisite intelligence, education and experience to make a significant contribution to the Board and bring a range of skills, diverse perspectives and backgrounds to its deliberations; and should have the highest ethical standards, a strong sense of professionalism and intense dedication to serving the interests of our stockholders. The following are qualifications, experience and skills for Board members which are important to our business and its future:

Set forth below is current biographical information about our directors, including the qualifications, experience and skills that make them suitable for service as a director. Each listed director’s respective experience and qualifications described below led the Compensation, Nominating and Governance (“CNG”) Committee of our Board of Directors to conclude that such director is qualified to serve as a member of our Board of Directors.

~~Y. Michael Rice~~Amit Bhalla has served as a director of Navidea sinceMay 2021.Mr. Bhalla has served as the Chief Financial Officer of Infinity BiologiX, LLC since November 2020. From 2015 to 2020, he served as Senior Healthcare Analyst for Lord, Abbett & Co as well as Investment Council Member for Lord, Abbett’s Healthcare Fund. Prior to that, Mr. Bhalla served in various roles including Vice President-Global Strategy & Development for Becton, Dickinson and Company, Director-Equity Research-Life Science Tools/Medical Technology for Citi, Vice President-Equity Research-Emerging Medical Technology and Analyst-Equity Research-Specialty Pharmaceuticals for Morgan Stanley, and Associate-Technical Operations/Research & Development for Johnson & Johnson’s Ortho-McNeil Pharmaceutical. Mr. Bhalla received his B.S. in biology from Cornell University and his M.B.A. from Tepper School of Business at Carnegie Mellon University.

Alexander L. Cappello has served as a director of Navidea since July 2021. Mr. Cappello has led several public and private companies over the past 48 years, including Cappello Global, LLC, a global investment bank, whose principals have transacted business in over 55 countries. He is also a director of The Cheesecake Factory Incorporated (Nasdaq), lead director of Virco Manufacturing Corporation (Nasdaq), lead director of The Agnew Companies and Caldera Medical Corp. Mr. Cappello is a director of RAND Corporation’s Center for Middle East Public Policy, the Center for Global Risk and Security, and the RAND-Russia Forum. Mr. Cappello is a former Chairman of Intelligent Energy, PLC (LSE), Inter-Tel (Nasdaq), and Geothermal Resources Intl. (AMEX), and a former director of Nano Financial Holdings and California Republic Bank. He is also a former advisor to the board of Gusmer Enterprises and former trustee of University of Southern California, and trustee and chairman of the investment committee of City of Hope. Mr. Cappello received a B.S. in management and finance from the Marshall School of Business at the University of Southern California.

John K. Scott, Jr. has served as a director of Navidea since ~~May 2016.~~ July 2021.Mr. ~~Rice~~Scott has served as the owner and manager of PCS, Inc. since 1997, where he is aresponsible for directing the acquisition, financing, sales and operations for land entitlement and development for privately owned condominium, apartment, hotel, single family and retail projects in California, Colorado and Texas. He has also served as the general partner of ~~LifeSci Advisors, LLC~~NJD, Ltd., a Texas limited partnership, since 1997 and ~~LifeSci Capital, LLC, companies which he co-founded~~as the managing member of Merging Interests, Inc. since 1980. Mr. Scott also has extensive experience in ~~March 2010. Prior to co-founding LifeSci Advisors~~conducting due diligence, feasibility studies, financial analysis, cost estimates and ~~LifeSci Capital,~~transaction negotiations for the purchase, lease, development, marketing and sale of projects and properties. Mr. ~~Rice was the co-head of health care investment banking at Canaccord Adams, where he was involved~~Scott earned a B.S. in ~~debt~~agricultural economics with an emphasis on construction management and equity financing. Mr. Rice was also a Managing Director at ThinkEquity Partners where he was responsible for managing Healthcare Capital Markets, including the structuring and execution of numerous transactions. Prior to that, Mr. Rice served as a Managing Director at Bank of America serving large hedge funds and private equity healthcare funds. Previously, he was a Managing Director at JPMorgan/Hambrecht & Quist. Mr. Rice currently serves on the board of directors of RDD Pharma, a specialty pharmaceuticals company. Mr. Rice received a B.A.real estate from the University of ~~Maryland.~~

~~S. Kathryn Rouan, Ph.D.~~, has served as a director of Navidea since December 2018. Dr. Rouan most recently served as the SVP and Head of Projects, Clinical Platforms and Sciences (“PCPS”) at GlaxoSmithKline (“GSK”) from May 2016 to November 2018 following a 29-year career at GSK. The PCPS organization within GSK encompasses the Global Clinical Operations, Statistics and Programming, Clinical Pharmacology, GCP Quality, Third Party Resourcing and Project Management functions and includes approximately 1,800 staff in 20 countries. Dr. Rouan first joined GSK in 1989 with a background in Pharmaceutical Sciences, focusing on formulation development of protein pharmaceuticals. In 1993, Dr. Rouan moved into Project Leadership and Management becoming VP and Head of Metabolism and Pulmonary Project Management in 1999. She continued to lead Projects in a number of Therapeutic areas including Cardiovascular, Immunoinflammation and Gastroenterology Therapy areas. In 2007, Dr. Rouan led the development, submission and approval of Arzerra (ofatumumab) in refractory chronic lymphocytic leukemia. In 2012, she became Head of Biopharmaceutical Development responsible for delivery of GSK’s portfolio of biopharmaceutical medicines. In December 2013, Dr. Rouan was appointed SVP and Head of R&D Stiefel, GSK’s Dermatology therapy area unit. Dr. Rouan holds a Ph.D. in Pharmaceutical Sciences from the University of Rhode Island, and a B.Pharm. from the University of London.

~~Adam D. Cutler~~ has served as a director of Navidea since December 2018. Mr. Cutler is a biotechnology executive with over 20 years of experience in equity research, investor relations, capital markets, business development, finance, and management consulting. Mr. Cutler joined Molecular Templates, Inc. as its Chief Financial Officer in November 2017. Prior to that, he was Senior Vice President of Corporate Affairs for Arbutus Biopharma Corporation, where he was responsible for investor relations and contributed to the company’s business development and corporate finance efforts from March 2015 to November 2017. From 2012 to 2015, he was a Managing Director for The Trout Group LLC and Trout Capital LLC, where he executed financings and advised public and private life science companies on investor relations and capital raising strategies. From 2000 to 2012, Mr. Cutler worked as a biotechnology equity research analyst with Credit Suisse, Canaccord Genuity, JMP Securities, and Bank of America Securities. He also worked in healthcare consulting as an Analyst at The Frankel Group and a Consultant for Ernst & Young LLP. He currently serves on the Board of Directors for Inmed Pharmaceuticals. He earned his Bachelor of Arts degree in Economics from Brandeis University.

~~Jed A. Latkin~~ has served as Chief Executive Officer of Navidea since October 2018, and as Chief Operating Officer and Chief Financial Officer of Navidea since May 2017. Mr. Latkin also served as Interim Chief Operating Officer of Navidea from April 2016 to April 2017. Mr. Latkin has more than twenty years of experience in the financial industry supporting many investments in major markets including biotechnology and pharmaceuticals. He most recently was employed by Nagel Avenue Capital, LLC since 2010 and in that capacity he provided contracted services as a Portfolio Manager, Asset Based Lending for Platinum Partners Value Arbitrage Fund L.P. Mr. Latkin has been responsible for a large diversified portfolio of asset-based investments in varying industries, including product manufacturing, agriculture, energy, and healthcare. In connection with this role, he served as Chief Executive Officer of End of Life Petroleum Holdings, LLC and Black Elk Energy, LLC, Chief Financial Officer of Viper Powersports, Inc. and West Ventures, LLC, and Portfolio Manager of Precious Capital, LLC. Mr. Latkin served on the Board of Directors for Viper Powersports, Inc. from 2012 to 2013 and served on the boards of directors of the Renewable Fuels Association and Buffalo Lake Advanced Biofuels. Mr. Latkin earned a B.A from Rutgers University and a M.B.A. from Columbia Business School.Wisconsin.

~~Claudine Bruck, Ph.D.~~Malcolm G. Witter, has served as a director of Navidea since ~~March 2018. Dr. Bruck is co-founder~~December 2020. Mr. Witter has over 40 years of operational and ~~has served~~investment leadership experience, serving as investment banker, Chief ~~Executive~~Financial Officer, of Prolifagen LLC, a start-up company developing a microRNA-based medicine for tissue regeneration, since June 2016. She is also a course director at University of Pennsylvania’s Institute of Translational Medicine and ~~Applied Technology, a consultant~~advisor to ~~BioMotiv LLC~~many companies and a member of the board of directors of QRPharma, a biotechnology company focused on development of medicines for neurodegenerative diseases. Dr. Bruck joined GlaxoSmithKline (“GSK”) to build GSK’s HIV vaccine program in 1985. In her role in GSK’s vaccine group, Dr. Bruck was instrumental in the development of GSK’s HPV vaccine (Cervarix), and headed their cancer vaccine program from inception to Phase 2 before joining the drug discovery group of GSK. She held several roles in the drug discovery group, from Head of Clinical Immunology (2004-2005) to VP and Head of Biology for the Center of Excellence for External Drug Discovery (2005-2008), to VP and Head of a newly formed ophthalmology R&D group (2008-2015). Dr. Bruck has a Ph.D. in Biochemistry from the University of Brussels. She was a post-doctoral student at Harvard University Medical School and an Assistant Professor at Tufts Medical School.

~~Michael M. Goldberg, M.D.~~ ~~served as a director of Navidea from November 2013 to August 2018 and as President and Chief Executive Officer of Navidea from September~~private organizations. From 2016 to August 2018. Dr. Goldberg has been a Managing Partner of Montaur Capital Partners since January 2007. From 2007 to 2013 Dr. Goldberg managed a life science investment portfolio for Platinum Partners called Platinum-Montaur Life Sciences, LLC. Prior to that, Dr. Goldberg served as the Chief Executive Officer of Emisphere Technologies, Inc., from August 1990 to January 2007 and as its President from August 1990 to October 1995. He also served on Emisphere’s board of directors from November 1991 to January 2007. Previous to that, Dr. Goldberg served as Vice President of The First Boston Corp., where he was a founding member of the Healthcare Banking Group. Dr. Goldberg has been a Director of Echo Therapeutics, Inc., AngioLight, Inc., Urigen Pharmaceuticals, Inc., Alliqua BioMedical, Inc., and ADVENTRX Pharmaceuticals, Inc. Dr. Goldberg received a B.S. degree from Rensselaer Polytechnic Institute, an M.D. from Albany Medical College of Union University in 1982, and an M.B.A. from Columbia University Graduate School of Business in 1985.

~~Mark I. Greene M.D., Ph.D., FRCP~~served as a director of Navidea from March 2016 to August 2018. Dr. Greene has been Director of the Division of Immunology, Department of Pathology at University of Pennsylvania School of Medicine since 1986. Dr. Greene was the Associate Director of the Division for Fundamental Research, University of Pennsylvania Cancer Center from 1987-2009 and has been the John Eckman Professor of Medical Science of the University of Pennsylvania School of Medicine since 1989. From 1980 to 1986 he served as an Associate Professor of both Harvard University and Harvard Medical School. His groundbreaking work in erbB receptor function led to the development of Herceptin (Genentech) and to the development of a proprietary method for the rapid, reliable design of allosteric inhibitors of receptors and enzymes. Dr. Greene previously served as a scientific advisor to Navidea’s subsidiary, Macrophage Therapeutics, Inc., Ception Therapeutics, Antisome PLC and Fulcrum Technologies and also served as a Member of the Scientific Advisory Boards of Fulcrum Pharmaceuticals, Inc. and Tolerx, Inc. He previously served as an Emeritus Director of Emisphere Technologies, Inc. where he also served as a Director. Additionally, Dr. Greene previously served as a Director of Ribi Immunochem Research, Inc. and currently serves as a Consultant to Martell Biosystems, Inc. Dr. Greene also serves as an advisor to Belgene, SternGreene and Abzed, all start-up companies. Dr. Greene has an outstanding record of contributions to cancer biology and drug discovery that is well-documented in over 400 publications. Dr. Greene is a recipient of many awards and patents and has collaborated with a number of pharmaceutical companies. He received his M.D. (1972) and Ph.D. (1977) from the University of Manitoba, Canada, became a Fellow of the Royal College in 1976 and then joined the faculty of Harvard Medical School in 1976.

~~Eric K. Rowinsky, M.D.~~ served as a director of Navidea from July 2010 to March 2018. Dr. Rowinsky has served as Executive Chairman, President, and Head of the Scientific Advisory Board of RGenix, Inc, as well as the Chief Scientific Officer of Clearpath Development Co., which rapidly advances development stage therapeutic assets to pre-defined human Proof-of-Concept milestones, since June 2015. He has also served as the Head of Research and Development, Executive Vice President, and Chief Medical Officer of Stemline Therapeutics, Inc. from 2012 to 2015, and was the Founder of and served as Chief Executive Officer of Primrose Therapeutics from August 2010 to September 2011 at which time it was acquired by Stemline. From 2005 to 2009,2021, he served as the ~~Chief Medical Officer and Executive Vice President of Clinical~~Corporate Development ~~and Regulatory Affairs of ImClone Systems Incorporated,~~Regional Manager for USI Insurance Services (“USI”) where he was responsible for acquiring independent insurance agencies. From 2010 to 2016, Mr. Witter was Business Development Manager for Kibble & Prentice, Inc., a ~~life sciences company, which was acquired by Eli Lilly.~~USI company. Prior to ~~that, Dr. Rowinsky~~USI, Mr. Witter held ~~several positions~~roles at ~~the Cancer Therapy~~multiple financial institutions including Kibble & ~~Research Center’s Institute of Drug Development, including Director~~Prentice Financial, Compass Capital Fund Management, Bear, Stearns & Co., and Dean Witter Reynolds. Mr. Witter is a director of the ~~Institute, Director of Clinical~~Dean Witter Foundation and an Advisor to American Research ~~and SBC Endowed Chair for Early Drug Development, and concurrently served as Clinical Professor of Medicine in~~Capital. Mr. Witter received his M.B.A. from the ~~Division of Medical Oncology at the University of Texas Health Science Center at San Antonio. Dr. Rowinsky was an Associate Professor of Oncology at the Johns Hopkins University~~Stanford Graduate School of Medicine and on active staff at the Johns Hopkins School of Medicine from 1987 to 1996. Dr. Rowinsky is currently a member of the boards of directors of Biogen Idec, Inc., Verastem, Inc. and Fortress Biotech, Inc., and has served on the board of directors of BIND Therapeutics, Inc., all publicly-held life science companies. He is also an Adjunct Professor of Medicine at New York University. Dr. Rowinsky has extensive research and drug development experience, oncology expertise, corporate strategy, and broad scientific and medical knowledge.Business.

~~In addition to Mr. Latkin, the~~The following ~~individual is a senior~~individuals are executive ~~officer~~officers of Navidea and ~~serves~~serve in the ~~position~~positions indicated below:

Michael S. Rosol, Ph.D., has served as Chief Medical Officer of Navidea since December 2018. Prior to joining Navidea, Dr. Rosol served as Associate Director in the Clinical and Translational Imaging Group at Novartis Institutes for BioMedical Research from November 2016 to December 2018. Before that, he held positions as Senior Director of Business Development at Elucid Bioimaging, Inc. where he drove adoption of its Computer-Aided Phenotyping applications from May 2016 to November 2016, and as Chief Scientific Officer of MediLumine, Inc. from October 2015 to May 2016. Prior to those roles, he was the Head of the Translational Imaging Group at Novartis Pharmaceuticals Group from October 2012 to March 2015. His training and experience lie in the fields of biophysics, physiology, and biological/medical imaging, and his work has focused on cardiovascular imaging, preclinical and clinical imaging instrumentation and applications, animal models of human disease, pathophysiology, biomarkers, and imaging in toxicological and clinical trials. He has also served as faculty in Radiology and Director of two academic research imaging facilities. Dr. Rosol holds a Ph.D. from Boston University School of Medicine.

Michel Mikhail, Ph.D. has served as Chief Regulatory Officer of Navidea since October 2021. Dr. Mikhail has more than 30 years of experience in the pharmaceutical industry and a track record of achievement in R&D and international regulatory affairs at large multinational research-based pharmaceutical companies. Prior to joining Navidea, Dr. Mikhail worked in global regulatory consulting for various pharmaceutical and biotech companies from January 2016 through September 2021. Before acting as a consultant, Dr. Mikhail served in senior regulatory executive roles at BioNTech AG, Fresenius Kabi, Ranbaxy Europe Ltd. (now SunPharma), Pharmacia & Upjohn (now Pfizer), Knoll AG (now Abbvie), SmithKline Beecham (now GlaxoSmithKline), and Boehringer Ingelheim. Dr. Mikhail is a global expert in Regulatory Affairs dealing with the U.S. Food and Drug Administration (“US-FDA”), the European Medicines Agency (“EU-EMA”) as well as national agencies in Europe, Japan’s Pharmaceuticals and Medical Devices Agency, China’s National Medical Products Administration, among other regulatory agencies worldwide. Dr. Mikhail holds a Ph.D. from the University of Paris and a D.V.M. from the University of Hannover.

Erika L. Eves has served as Vice President, Finance and Administration of Navidea since November 2020. Ms. Eves has served the Company in several roles of increasing responsibility beginning in March 1992, including Accounting Clerk, Staff Accountant, Senior Accountant, Controller and Director of Finance and Administration. In addition to directing the financial operations of the Company, she is responsible for internal and external financial reporting including all SEC filings, maintaining a system of internal controls, and managing banking and vendor relationships. Ms. Eves earned a B.S.B.A. in Accounting from The Ohio State University and is a Certified Public Accountant.

Delinquent Section ~~16(a) Beneficial Ownership Reporting Compliance~~16 Filings

Section 16(a) of the Exchange Act requires our officers and directors, and greater than 10% stockholders, to file reports of ownership and changes in ownership of our securities with the ~~Securities and Exchange Commission.~~SEC. Copies of the reports are required by SEC regulation to be furnished to us. Based on our review of these reports and written representations from reporting persons, we believe that all reporting persons complied with all filing requirements during the fiscal year ended December 31, ~~2018,~~2021, except for: ~~(1) Frederick O. Cope,~~(i) former directors Claudine Bruck, Ph.D., Thomas F. Farb, S. Kathryn Rouan, Ph.D. and Agnieszka Winkler, who each had one late Form 4 filing related to stock issued in ~~lieu~~partial payment of director fees, (ii) Messrs. Cappello, Scott and Witter, who each had one late Form 4 filing related to stock issued in partial payment of director fees, (iii) Mr. Bhalla, who had two late Form 4 filings related to stock issued in partial payment of director fees, (iv) Dr. Mikhail, who had one late Form 4 filing related to a ~~portion of his annual cash bonus; (2) John K. Scott, Jr.,~~stock option award and (v) Mr. Farb and Ms. Winkler, who each had one late Form 3 filing ~~related~~due to ~~stock purchased in a private placement; (3) S. Kathryn Rouan, Ph.D., who had one late Form 3 filing resulting from~~ delays in obtaining ~~new EDGAR~~SEC filer codes; and (4) Michael M. Goldberg, M.D., who did not file a Form 4 related to the 18.5 million shares issued to him in November 2018. Dr. Goldberg was no longer an officer or director of Navidea at the time the 18.5 million shares were issued to him.codes.

We have adopted a code of business conduct and ethics that applies to our directors, officers and all employees. The code of business conduct and ethics is posted on our website at ~~www.navidea.com.~~www.navidea.com. The code of business conduct and ethics may also be obtained free of charge by writing to Navidea Biopharmaceuticals, Inc., Attn: Chief Financial Officer, 4995 Bradenton Avenue, Suite 240, Dublin, Ohio 43017.

Our Board of Directors is responsible for establishing broad corporate policies and reviewing our overall performance rather than day-to-day operations. The primary responsibility of our Board is to oversee the management of Navidea and, in doing so, serve the best interests of the Company and our stockholders. Our Board selects, evaluates and provides for the succession of executive officers and, subject to stockholder election, directors. It reviews and approves corporate objectives and strategies, and evaluates significant policies and proposed major commitments of corporate resources. Our Board also participates in decisions that have a potential major economic impact on the Company. Management keeps our directors informed of Company activity through regular communication, including written reports and presentations at Board and committee meetings.

Our Board of Directors held a total of ~~seven~~29 meetings in the fiscal year ended December 31, ~~2018,~~2021, and each of the directors attended at least 75 percent of the aggregate number of meetings of the Board of Directors and committees (if any) on which he or she ~~served, except for Dr. Rowinsky.~~served. It is our policy that all directors attend the Annual Meeting of Stockholders. However, conflicts and unforeseen events may prevent the attendance of a director, or directors. Due to the public health impact of the ongoing COVID-19 pandemic, the 2021 Annual Meeting of Stockholders was held as a virtual meeting. All then-current members of our Board of Directors attended the ~~2018~~2021 Annual Meeting of Stockholders either in ~~person.~~person or via webcast.

The Board of Directors maintains the following committees to assist it in its oversight responsibilities. The current membership of each committee is indicated in the list of directors set forth under “Board of Directors” above.

The Audit Committee of the Board of Directors selects our independent registered public accounting firm with whom the Audit Committee reviews the scope of audit and non-audit assignments and related fees, the accounting principles that we use in financial reporting, and the adequacy of our internal control procedures. The current members of our Audit Committee ~~are: Adam D. Cutler~~are Malcolm G. Witter (Chair), ~~Claudine Bruck, Ph.D.,~~Amit Bhalla and ~~Y. Michael Rice,~~Alexander L. Cappello, each of whom is “independent” under Section 803A of the NYSE American Company ~~Guide. From August 14, 2018 through January 1, 2019, the members~~Guide, and each of our Audit Committee were: Mr. Rice (Chair) and Dr. Bruck. From March 15, 2018 to August 14, 2018, the members of our Audit Committee were: Mr. Rice (Chair), Dr. Bruck and Dr. Greene. From January 1, 2018 to March 15, 2018, the members of our Audit Committee were: Mr. Rice (Chair), Dr. Greene and Dr. Rowinsky. The Board of Directors has determined that Mr. Cutler and Mr. Rice meetwhom meets the requirements of an “audit committee financial expert” as set forth in Section 407(d)(5) of Regulation S-K promulgated by the SEC. The Audit Committee held four meetings in the fiscal year ended December 31, ~~2018.~~2021. The Board of Directors adopted a written Amended and Restated Audit Committee Charter on April 30, 2004. A copy of the Amended and Restated Audit Committee Charter is posted on the Company’s website at ~~www.navidea.com.~~www.navidea.com.

The CNG Committee of the Board of Directors discharges the Board’s responsibilities relating to the compensation of the Company's directors, executive officers and associates, identifies and recommends to the Board of Directors nominees for election to the Board, and assists the Board in the implementation of sound corporate governance principles and practices. With respect to its compensation functions, the CNG Committee evaluates and approves executive officer compensation and reviews and makes recommendations to the Board with respect to director compensation, including incentive or equity-based compensation plans; reviews and evaluates any discussion and analysis of executive officer and director compensation included in the Company’s annual report or proxy statement, and prepares and approves any report on executive officer and director compensation for inclusion in the Company’s annual report or proxy statement required by applicable rules and regulations; and monitors and evaluates, at the Committee’s discretion, matters relating to the compensation and benefits structure of the Company and such other domestic and foreign subsidiaries or affiliates, as it deems appropriate. The members of our CNG Committee ~~are: Claudine Bruck, Ph.D.~~are Malcolm G. Witter (Chair), ~~Adam D. Cutler, Y. Michael Rice,~~Alexander L. Cappello and ~~S. Kathryn Rouan, Ph.D.~~John K. Scott, Jr. The CNG Committee ~~did not hold any~~held 11 meetings in the fiscal year ended December 31, ~~2018 because compensation- and nomination-related discussions were held by the full Board.~~2021. The Board of Directors adopted a written Compensation, Nominating and Governance Committee Charter on February 26, 2009. A copy of the Compensation, Nominating and Governance Committee Charter is posted on the Company’s website at ~~www.navidea.com.~~www.navidea.com.

The Board Oversight Committee of the Board of Directors provides support and guidance to the Company’s Executive Leadership Committee. In November 2021, following the resignation of the Company’s former Chief Executive Officer, Chief Operating Officer and Chief Financial Officer, Jed. A. Latkin, our Board of Directors established an Executive Leadership Committee to lead the Company on an interim basis while its next CEO is identified. The Executive Leadership Committee includes Michael S. Rosol, Ph.D., our Chief Medical Officer, Erika L. Eves, our Vice President of Finance and Administration and Jeffrey G. Smith, our Vice President of Operations. The current members of the Board Oversight Committee are Alexander L. Cappello and John K. Scott, Jr.

Overview of Compensation Program. The CNG Committee of the Board of Directors is responsible for establishing and implementing our compensation policies applicable to senior executives and monitoring our compensation practices. The CNG Committee seeks to maintain compensation plans that are fair, reasonable and competitive. The CNG Committee is responsible for reviewing and approving senior executive compensation, awards under our cash bonus plan, and awards under our equity-based compensation plans.

Philosophy and Goals of Executive Compensation Plans. The CNG Committee’s philosophy for executive compensation is to:

To assess whether our programs are competitive, the CNG Committee reviews compensation information of peer companies, national data and trends in executive compensation to help determine the appropriateness of our plans and compensation levels. These reviews, and the CNG Committee’s commitment to pay for performance, become the basis for the CNG Committee’s decisions on compensation plans and individual executive compensation payments.

The CNG Committee has approved a variety of programs that work together to provide a combination of basic compensation and strong incentives. While it is important for us to provide certain base level salaries and benefits to remain competitive, the CNG Committee’s objective is to provide compensation plans with incentive opportunities that motivate and reward executives for consistently achieving superior results. ~~The~~he CNG Committee designs our compensation plans to:

The CNG Committee reviews ~~individual~~senior executive compensation levels at least annually. During the review process, the CNG Committee addresses the following questions:

In addressing these questions, the CNG Committee considers input from management, outside compensation experts and published surveys of compensation levels and practices.

The CNG Committee does not believe that our compensation policies and practices for our employees give rise to risks that are reasonably likely to have a material adverse effect on the Company. ~~As noted below, our~~Our incentive-based compensation ~~has historically been~~goals are generally tied to ~~Company financial performance (e.g., revenue, gross margin or budgeted expense targets) or~~ product development goals (e.g., clinical trial progress or regulatory milestones)~~. Following the Asset Sale to Cardinal Health 414 in March 2017, incentive-based compensation~~ or Company financial goals ~~have been more focused on development goals as we work to develop additional product candidates.~~(e.g., budgeted expense targets or business partnerships). The CNG Committee believes that the existence of these performance incentives creates a strong motivation for Company employees to contribute towards the achievement of strong, sustainable performance, and believes that the Company has a strong set of internal controls that minimize the risk that financial performance can be misstated in order to achieve incentive compensation payouts.

In addition to the aforementioned considerations, the CNG Committee also takes into account the outcome of stockholder advisory (“say-on-pay”) votes on the compensation of our Chief Executive Officer ~~Chief Financial Officer,~~ and our next ~~three~~two highest-paid executive officers (the “Named Executive Officers”). At the Annual Meeting of Stockholders held on ~~June 29, 2017,~~September 14, 2021, approximately ~~75%~~79% of our stockholders who cast a ballot voted in favor of the resolution relating to the compensation of our Named Executive Officers. The CNG Committee believes this vote affirmed our stockholders’ support of the Company’s executive compensation program. The CNG Committee will continue to consider the results of future say-on-pay votes when making future compensation decisions for the executive officers. Also at the Annual Meeting of Stockholders on June 29, 2017, approximately 40% of our stockholders, representing the most votes received, voted in favor of holding “say-on-pay” votes every two years. In accordance with the results of this vote, theThe Company ~~will hold~~currently holds an advisory vote to approve the compensation of the Company’s Named Executive Officers every two ~~years~~years. The two-year frequency of advisory “say-on-pay” votes will continue until the next required vote on the frequency of advisory votes on executive compensation at the Company’s Annual Meeting of Stockholders to be held in 2023.

Scope of Authority of the CNG Committee. The Board of Directors has authorized the CNG Committee to establish the compensation programs for all executive officers and to provide oversight for compliance with our compensation philosophy. The CNG Committee delegates the day-to-day administration of the compensation plans to management (except with respect to our executive officers), but retains responsibility for ensuring that the plan administration is consistent with the Company’s policies. Annually, the CNG Committee ~~sets~~recommends the compensation for our executive officers, including objectives and awards under incentive plans. The Chief Executive Officer provides input for the CNG Committee regarding the performance and appropriate compensation of the other officers. The CNG Committee gives considerable weight to the Chief Executive Officer’s evaluation of the other officers because of his or her direct knowledge of each officer’s performance and contributions. The CNG Committee also makes recommendations to the Board of Directors on appropriate compensation for the non-employee directors. In addition to overseeing the compensation of executive officers, the CNG Committee recommends or approves awards under short-term cash incentive and long-term equity-based compensation plans for all other employees. For more information on the CNG Committee’s role, see the CNG Committee’s charter, which can be found on our website at ~~www.navidea.com.~~www.navidea.com.

Independent Compensation Expertise. The CNG Committee is authorized to periodically retain independent experts to assist in evaluating executive compensation plans and in setting executive compensation levels. These experts provide information on trends and best practices so the CNG Committee can formulate ongoing plans for executive compensation. The CNG Committee retained Board Advisory, LLC (“Board Advisory”) as its independent consultant to assist in the determination of the reasonableness and competitiveness of the compensation levels of its ~~President and Chief~~Named Executive ~~Officer for fiscal 2018, and of its Chief Executive Officer, Chief Operating Officer, and Chief Financial Officer, Chief Medical Officer,~~Officers and Board of Directors for fiscal ~~2019.~~2021. No conflict of interest exists that would prevent Board Advisory from serving as independent consultant to the CNG Committee.

For fiscal ~~2018, Board Advisory performed a benchmark compensation review of our President and Chief Executive Officer. For fiscal 2019,~~2021, Board Advisory performed a benchmark compensation review of our key executive positions, including our Chief Executive Officer, Chief Operating Officer, and Chief Financial Officer, Chief Medical Officer, Chief Business Officer, and our Board of Directors. Board Advisory utilized published survey and proxy reported data from compensation peers, with market data aged to ~~February 1, 2018 and~~ January 1, ~~2019, respectively,~~2021, by an annualized rate of 3.0%, the expected pay increase in ~~both 2018 and 2019~~2021 for executives in the life sciences industry.

In evaluating appropriate executive compensation, it is common practice to set targets at a point within the competitive marketplace. The CNG Committee sets its competitive compensation levels based upon its compensation philosophy. Following completion of the Board Advisory study for ~~2019,~~2021, the CNG Committee noted that the total cash compensation of our Chief Executive Officer, Chief Operating Officer and Chief Financial Officer iswas between the 50^th and 75^th percentile for an established peer group of companies. The CNG Committee also noted that the total cash compensation of our Chief Medical Officer ~~is significantly~~was below the ~~market rate~~25^th percentile, and the total cash compensation of our Chief Business Officer was between the 25^th and 50^th percentile for ~~this position.~~these positions.

Peer Group Companies. ~~In addition to independent survey analysis, in 2018 and 2019 the CNG Committee reviewed~~As part of their review, Board Advisory surveyed the compensation levels at specific competitive benchmark companies. With input from management, ~~the CNG Committee~~Board Advisory chose the peer companies because they are developmental life sciences companies ~~have~~and are similar to Navidea in revenue, invested capital, market capitalization, ~~between~~and employees. The selected peer group companies have invested capital of less than four times that of Navidea, or approximately ~~$20 million and $350~~$375 million, and have comparable key executive positions. While the specific plans for these companies may or may not be used, it is helpful to review their compensation data to provide benchmarks for the overall compensation levels that will be used to attract, hire, retain and motivate our executives.

As competitors and similarly situated companies that compete for the same executive talent, the CNG Committee determined that the following peer group companies most closely matched the responsibilities and requirements of our executives:

Board Advisory ~~and the CNG Committee~~ used the publicly available compensation information for these companies to analyze our competitive position in the industry. Base salaries and short-term and ~~long term~~long-term incentive plans of the executives of these companies were reviewed to provide background and perspective in analyzing the compensation levels for our executives.

Base Salary. Using information gathered by Board Advisory, peer company data, national surveys, general compensation trend information and recommendations from management, the CNG Committee approved the fiscal 2018 base salary for our President and Chief Executive Officer. Base salaries for senior executives are set using the CNG Committee’s philosophy that compensation should be competitive and based upon performance. Executives should expect that their base salaries, coupled with a cash bonus award, would provide them the opportunity to be compensated at or above the competitive market at the 40th to ~~50th~~60th percentile.

Based on competitive reviews of similar positions, industry salary trends, overall company results and individual performance, salary increases may be approved from time to time. The CNG Committee reviews and approves base salaries of all executive officers. In setting specific base salaries for fiscal ~~2018,~~2021, the CNG Committee considered published proxy data for similar positions at peer group companies.

The following table shows the changes in base salaries for the Named Executive Officers that were approved for fiscal ~~2018~~2021 compared to the approved salaries for fiscal ~~2017:~~2020:

The following table shows the base salaries for the Named Executive Officers that were approved for fiscal ~~2019~~2022 compared to the approved salaries for fiscal ~~2018:~~2021:

Short-Term Incentive Compensation. Our executive officers, along with ~~all of~~ our other employees, are eligible to participate in our annual cash bonus program, which has four primary objectives:

The cash bonus compensation plan provides each participant with an opportunity to receive an annual cash bonus based on our Company’s performance during the fiscal year. Cash bonus targets for senior executives are determined as a percentage of base salary, based in part on published proxy data for similar positions at peer group companies. The following are the key provisions of the cash bonus compensation ~~plan:~~plan for our Named Executive Officers:

~~In June 2018, the Board of Directors established the fiscal 2018 targets and performance measures for all Company employees.~~ For fiscal ~~2018,~~2021, the cash bonus for each executive officer was a function of the designated target bonus amount and certain business performance objectives, weighted as a percentage of the total target amount. The business performance objectives established for fiscal ~~2018~~2021 were as follows:

For fiscal ~~2018,~~2021, the Board of Directors determined the cash bonus targets for Named Executive Officers as follows:

On ~~February 7, 2019,~~January 5, 2022, the Board of Directors determined the amounts to be awarded as ~~2018~~2021 bonuses to all employees, including the Named Executive Officers. The Board of Directors recognized the achievement of ~~all 2018~~approximately 76% of 2021 bonus goals and thus awarded bonuses at ~~100%~~76% of target amounts for all ~~employees.~~employees, including the Named Executive Officers, to be paid in cash 50% immediately and 50% following successful fundraising. Employees who separated from the Company during 2021, including Mr. Latkin and Mr. Kaufman, did not receive a cash bonus award related to fiscal 2021.

Long-Term Incentive Compensation. All Company employees are eligible to receive equity awards in the form of stock options or restricted stock. Equity instruments awarded under the Company’s equity-based compensation plan are based on the following criteria:

Although equity awards may be made at any time as determined by the CNG Committee, they are generally made to all full-time employees once per year, or on the recipient’s hire date in the case of new-hire grants.

Equity-based compensation is an effective method to align the interests of stockholders and management and focus management’s attention on long-term results. When awarding equity-based compensation the CNG Committee considers the impact the participant can have on our overall performance, strategic direction, financial results and stockholder value. Therefore, equity awards are primarily based upon the participant’s position in the organization, competitive necessity and individual performance. Stock option awards have vesting schedules over several years to promote long-term performance and retention of the recipient, and restricted stock awards may include specific performance criteria for vesting or vest over a specified period of time. ~~We did not grant equity awards~~

In February 2021, the Company awarded options to ~~our Named Executive Officers~~purchase 25,000, 12,500, 100,000 and 25,000 shares of Common Stock to Dr. Rosol, Ms. Eves, Mr. Latkin and Mr. Kaufman, respectively, as part of their annual compensation packages. The options have an exercise price of $2.56 per share, and vest as to one-third of the options on each of the first three anniversaries of the date of grant. The options will expire on the tenth anniversary of the date of grant.

In November 2021, the Company awarded options to purchase 75,000 shares of Common Stock to Dr. Mikhail in ~~2018.~~connection with his employment as Chief Regulatory Officer. The options have an exercise price of $1.37 per share, and vest as to one-third of the options on each of the first three anniversaries of the date of grant. The options will expire on the tenth anniversary of the date of grant.

In December 2021, the Company awarded options to purchase 100,000 shares of Common Stock to Dr. Rosol. The options have an exercise price of $1.08 per share, and vest quarterly over four years beginning on April 1, 2022. The options will expire on the tenth anniversary of the date of grant.

Other Benefits and Perquisites. The Named Executive Officers are generally eligible to participate in other benefit plans on the same terms as other employees. These plans include medical, dental, vision, disability and life insurance benefits, and our 401(k) retirement savings plan (the “401(k) Plan”).

Our paid time off (“PTO”) policy allows employees to carry up to 40 hours of unused PTO time forward to the next fiscal year. Any unused PTO time in excess of the amount eligible for rollover is generally forfeited.

Our Named Executive Officers are considered “key employees” for purposes of Internal Revenue Code (“IRC”) Section 125 Plan non-discrimination testing. Based on such non-discrimination testing, we determined that our Section 125 Plan was “top-heavy” for fiscal 2017. Accordingly, our key employees were ineligible to participate in the Section 125 Plan and were unable to pay their portion of medical, dental, and vision premiums on a pre-tax basis during fiscal 2017. As a result, the Company reimbursed its key employees an amount equal to the lost tax benefit. For fiscal 2018, we have determined that our Section 125 Plan is no longer “top-heavy.” Accordingly, our key employees are eligible to participate in the Section 125 Plan and may pay their portion of medical, dental and vision premiums on a pre-tax basis beginning January 1, 2018.

We pay group life insurance premiums on behalf of all employees, including the Named Executive Officers. The benefit provides life insurance coverage at two times the employee’s annual salary plus $10,000, up to a maximum of $400,000.

We also pay group long-term disability insurance premiums on behalf of all employees, including the Named Executive Officers. The benefit provides long-term disability insurance coverage at 60% of the employee’s annual salary, up to a maximum of $10,000 per month, beginning 180 days after the date of disability and continuing through age 65.

401(k) Retirement Plan. All employees are given an opportunity to participate in our 401(k) Plan following a new-hire waiting period. ~~The~~Under the 401(k) Plan, ~~allows~~ participants tomay have pre-tax amounts, or post-tax amounts under a Roth option, withheld from their pay and provides for a discretionary employer matching contribution (currently, a ~~40%~~100% match up to 5%6% of salary in the form of our ~~common stock)~~Common Stock). Participants may invest their contributions in various fund options, but are prohibited from investing their contributions in our ~~common stock.~~Common Stock. Participants are immediately vested in both their contributions and Company matching contributions. The 401(k) Plan qualifies under section 401 of the Internal Revenue Code, which provides that employee and company contributions and income earned on contributions are not taxable to the employee until withdrawn from the Plan, and that we may deduct our contributions when made.

Employment ~~Agreements~~Agreement and Separation Agreement with Mr. Latkin

~~Jed A. Latkin~~.Effective July 27, 2020 through October 24, 2021, Mr. Latkin iswas employed under ~~a 24-month~~an employment agreement ~~effective through September 30, 2020. The employment agreement provides~~that provided for an annual base salary of ~~$475,000.~~$490,000. For the ~~calendar~~fiscal year ending December 31, ~~2018,~~2021, the CNG Committee determined that the maximum bonus payment to Mr. Latkin would be ~~$356,250.~~$367,500. No bonus was paid to Mr. Latkin due to his resignation prior to payment of bonuses in 2022.

On November 23, 2021, Mr. Latkin signed a Separation Agreement and General Release (the “Separation Agreement”) in connection with his resignation from his position as Chief Executive Officer, Chief Operating Officer and Chief Financial Officer, and as a director, on October 24, 2021 (the “Separation Date”). Pursuant to the Separation Agreement, among other things, the Company agreed to provide Mr. Latkin with certain separation benefits, commencing on the “Effective Date,” defined as the eighth day after Mr. Latkin signs, without revoking, the Separation Agreement. These separation benefits include continued payment of Mr. Latkin’s ~~employment agreement also provides for post-employment compensation based~~base salary of $490,000, less all relevant taxes and other withholdings, on the ~~reason~~following basis: (i) for ~~termination:~~12 months, 100% of his base salary, minus an aggregate $24,000 deducted monthly pro rata for reimbursement of Mr. Latkin’s attorney fees which were paid by the Company, and (ii) for 10 months following the expiration of the first 12-month period, 50% of his base salary. On the Effective Date, each of Mr. Latkin’s unvested stock options vested, and all of his vested stock options (covering 69,918 shares) and previously unvested options (covering 333,332 shares) may be exercised by Mr. Latkin on or before the earlier of the fifth anniversary of the Separation Date and the original expiration date. On the Effective Date, each of Mr. Latkin’s 33,333 outstanding unvested restricted stock units became fully vested, and all of such restricted stock units were settled within thirty days after the Separation Date, less applicable withholding in shares of common stock. The Company also agreed to reimburse Mr. Latkin for expenses incurred pursuant to Company policy. For purposes of assistance provided in certain litigation matters, the Company agreed to pay Mr. Latkin $250 per hour, subject to certain limitations. Mr. Latkin will also be entitled to receive, subject to his timely execution and non-revocation of the Separation Agreement, a payment equal to up to one percent of total capital raised during the twenty-two months following the Separation Date through one of two investment banking firms introduced to the Company by Mr. Latkin, less relevant taxes and withholdings and subject to certain payment terms. In addition, Mr. Latkin and the Company generally released each other from any and all claims each may have against the other.

The CNG Committee is responsible for establishing, reviewing and approving the Company’s compensation philosophy and policies, reviewing and making recommendations to the Board regarding forms of compensation provided to the Company’s directors and officers, reviewing and determining cash and equity awards for the Company’s officers and other employees, and administering the Company’s equity incentive plans.

In this context, the CNG Committee has reviewed and discussed with management the Compensation Discussion and Analysis included in this annual report on Form 10-K. In reliance on the review and discussions referred to above, the CNG Committee recommended to the Board, and the Board has approved, that the Compensation Discussion and Analysis be included in this annual report on Form 10-K for filing with the SEC.

Compensation, Nominating and Governance Committee Interlocks and Insider Participation

~~The current~~None of the members of our CNG Committee ~~are: Claudine Bruck, Ph.D. (Chair), Adam D. Cutler, Y. Michael Rice, and S. Kathryn Rouan, Ph.D. None of these individuals were at any time~~ during the ~~fiscal~~past year ~~ended December 31, 2018, or at any other time,~~was an officer or employee of the Company. None of our executive officers currently serves, or in the past year served, as a member of a compensation committee (or other committee serving an equivalent function) or director of any entity that has one or more executive officers serving on our CNG Committee or our Board of Directors.

No director who served on the CNG Committee during ~~2018~~2021 had any relationships requiring disclosure by the Company under the SEC’s rules requiring disclosure of certain relationships and related-party transactions. None of the Company’s executive officers served as a director or a member of a compensation committee (or other committee serving an equivalent function) of any other entity, the executive officers of which served as a director of the Company or member of the CNG Committee during ~~2018.~~2021.

The following table sets forth certain information concerning the annual and long-term compensation of our Named Executive Officers for the last ~~three~~two fiscal years. The compensation of our former Chief Executive Officer and former Chief Business Officer are also included.

The following table describes each component of the amounts shown in the “All Other Compensation” column in the Summary Compensation ~~table~~Table above.

As required by Section 953(b) of the Dodd-Frank Wall Street Reform and Consumer Protection Act of 2010 and Item 402(u) of Regulation S-K, we are providing the following information with respect to our last completed fiscal year. The pay ratio information provided below is a reasonable estimate calculated in a manner consistent with applicable SEC rules.

For 2018, we calculated (i) the annual total compensation of our Chief Executive Officer, (ii) the median of the annual total compensation of all of our employees other than the Chief Executive Officer, and (iii) the ratio of the annual total compensation of our Chief Executive Officer to the median of the annual total compensation of all other employees, as follows:

~~In determining the pay ratio information provided above, we first identified our median employee for 2018 by using the following methodology:~~

Once our median employee was identified in the manner described above, we calculated the annual total compensation of the median employee using the same methodology that we used to determine the annual total compensation of the CEO, as reported in the Summary Compensation Table.

The following table sets forth the expected benefit to be received by our Chief Executive Officer in the event of his termination resulting from various scenarios, assuming a termination date of December 31, 2018 and a stock price of $0.10, our closing stock price on December 31, 2018.

Effective August 14, 2018, Dr. Michael Goldberg resigned from his positions as an executive officer and a director of Navidea. In connection with Dr. Goldberg’s resignation, Navidea and Dr. Goldberg entered into the Agreement, with the intent of entering into one or more additional Definitive Agreements, which set forth the terms of his separation from service. The Agreement provides that Dr. Goldberg will be entitled to receive a severance of $978,000 payable in equal installments over two years, along with a one-time payment of approximately $35,000 which represents the cost of continuing his existing health care coverage for a period of 16 months. The Agreement also provides that Dr. Goldberg will be entitled to 23.5 million shares of common stock of Navidea, representing in part payment of accrued bonuses and payment of the balance of the Platinum Note. A portion of the 23.5 million shares to be issued to Dr. Goldberg will be held in escrow for up to 18 months in order to reimburse Navidea in the event that Navidea is obligated to pay any portion of the Platinum Note to a party other than Dr. Goldberg. Further, the Agreement provides that the Company’s subsidiary, MT, will redeem all of Dr. Goldberg’s preferred stock and issue to Dr. Goldberg super voting common stock equal to 5% of the outstanding shares of MT. On November 20, 2018, the Company issued 18.5 million shares of common stock of Navidea to Dr. Goldberg, 5 million of which were placed in escrow in accordance with the Agreement. As of the date of filing of this Annual Report on Form 10-K, the Definitive Agreements have not yet been signed.

On March 7, 2019, Dr. Goldberg filed a complaint against Navidea and MT in the United States District Court for the Southern District of New York. The Complaint alleges a breach of contract claim against both Navidea and MT for failure to pay to Dr. Goldberg funds allegedly due to him under the Platinum Note. The Complaint further alleges a breach of contract claim against Navidea due to Navidea’s failure to issue 23.5 million shares to Dr. Goldberg, to issue MT Super Voting Common Stock, by removing Dr. Greene from the MT Board of Directors, by appointing Mr. Rice and Dr. Bruck to the MT Board of Directors, and by terminating Dr. Goldberg as CEO of MT.

In making compensation decisions in 2017 and prior years, the CNG Committee often sought to structure certain incentive awards with the intention that they would be exempt from the $1 million deduction limit as “qualified performance-based compensation.” However, the committee never adopted a policy that would have required all compensation to be deductible, because the committee wanted to preserve the ability to pay compensation to our executives in appropriate circumstances, even if such compensation would not be deductible under Section 162(m) of the Internal Revenue Code (“Section 162(m)”).

The Tax Cuts and Jobs Act, which was enacted on December 22, 2017, included a number of significant changes to Section 162(m), of the Internal Revenue Code, such as the repeal of the qualified performance-based compensation exemption and the expansion of the definition of “covered employees” (for example, by including the chief financial officer and certain former ~~named executive officers~~Named Executive Officers as covered employees). As a result of these changes, except as otherwise provided in the transition relief provisions of the Tax Cuts and Jobs Act, compensation paid to any of our covered employees generally will not be deductible in ~~2018~~2021 or future years, to the extent that it exceeds $1 million.

The following table sets forth certain information about plan-based awards that we made to the Named Executive Officers during fiscal ~~2018.~~2021. For information about the plans under which these awards were granted, see the discussion under “Short-Term Incentive Compensation” and “Long-Term Incentive Compensation” in the “Compensation Discussion and Analysis” section above.

The following table presents certain information concerning outstanding equity awards held by the Named Executive Officers as of December 31, ~~2018.~~2021.

The following table presents, with respect to the Named Executive Officers, certain information about option exercises and restricted stock vested during fiscal ~~2018.~~2021.

~~Each~~From January 1, 2021 through November 15, 2021, each non-employee director received an annual ~~cash~~ retainer of ~~$50,000 during the fiscal year ended December 31, 2018.~~$50,000. The Chair of the Company’s Board of Directors received an additional annual retainer of ~~$30,000, the~~$30,000. Audit and CNG Committee members received an annual retainer of $2,500 for each committee on which they served. The Chair of the Audit Committee received an additional annual retainer of ~~$10,000,~~$7,500, and the Chair of the CNG Committee received an additional annual retainer of ~~$7,500~~$5,000 for their services in those ~~capacities during 2018. Non-Chair members~~capacities. Of the retainers earned from April 1, 2021 through November 15, 2021, 50% were paid in cash and 50% were paid in shares of common stock of the ~~Audit Committee received an additional annual retainer of $2,500 and non-Chair members~~Company, based on the closing market price of the ~~CNG Committee received an additional annual retainer~~stock at the end of ~~$2,500. We also reimbursed non-employee directors for travel expenses for meetings attended during 2018.~~

each quarter. Each non-employee director also received ~~50,000~~2,500 shares of restricted stock and ~~50,000~~2,500 options to purchase stock at ~~$0.75~~$2.28 per share during ~~2018~~2021 as a part of the Company’s annual stock incentive grants, in accordance with the provisions of the Navidea Biopharmaceuticals, Inc. 2014 Stock Incentive ~~Plan, except for Mr. Cutler and Dr. Rouan, who received their 2018 stock incentive grants in January 2019.~~Plan. The restricted stock and stock options granted will vest on the first anniversary of the date of grant. We also reimbursed non-employee directors for travel expenses for meetings attended during 2021.

In October 2021, the Board of Directors retained the services of a compensation consultant, F.W. Cook, to evaluate the compensation of the non-employee directors. Based on the recommendation of F.W. Cook, our Board of Directors has adopted a non-employee director compensation policy, beginning November 16, 2021. Under the policy, our non-employee directors are eligible to receive the following cash compensation for their services:

In addition, each non-employee director also received an annual retainer of 30,000 shares of unrestricted common stock, which are payable in equal monthly issuances over 12 months, as well as 30,000 shares of restricted stock that will vest as to one-third on each of the first three anniversaries of the date of grant. The policy also provides for the reimbursement of our non-employee directors for reasonable and documented travel expenses to attend meetings of our Board of Directors and committees of our Board of Directors.

The aggregate number of equity awards outstanding ~~at February 28, 2019~~as December 31, 2021 for each Director is set forth in the footnotes to the beneficial ownership table provided in ~~Part III, Item 12 of this Form 10-K.~~the section entitled “Principal Stockholders.” Directors who are also officers or employees of Navidea do not receive any compensation for their services as directors.

~~The CNG Committee has noted that the total compensation of our Board of Directors, including cash and equity awards, is at approximately the 50~~^th ~~percentile for our peer group of companies, while the total compensation of our Board Committee members is less than half of the competitive market rate.~~

The following table sets forth ~~certain~~ information concerning the compensation of our non-employee ~~Directors~~directors for the fiscal year ended December 31, ~~2018.~~2021.

Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters

The following table sets forth additional information as of December 31, ~~2018,~~2021, concerning shares of our ~~common stock~~Common Stock that may be issued upon the exercise of options and other rights under our existing equity compensation plans and arrangements, divided between plans approved by our stockholders and plans or arrangements not submitted to our stockholders for approval. The information includes the number of shares covered by, and the weighted average exercise price of, outstanding options and other rights and the number of shares remaining available for future grants excluding the shares to be issued upon exercise of outstanding options, warrants, and other rights.

Security Ownership of Principal Stockholders, Directors, Nominees and Executive Officers and Related Stockholder Matters

The following table sets forth, as of February 28, ~~2019,~~2022, certain information with respect to the beneficial ownership of shares of our ~~common stock~~Common Stock by: (i) each person known to us to be the beneficial owner of more than 5% of our outstanding shares of ~~common stock,~~Common Stock, (ii) each director or nominee for director of our Company, (iii) each of the Named Executive Officers (see “Executive Compensation – Summary Compensation Table”), and (iv) our directors and executive officers as a group. Except as indicated in the footnotes to this table, the persons named in the table have sole voting and investment power with respect to all shares of our common stock shown as beneficially owned by them, subject to community property laws, where applicable. Percentage ownership is based on 30,301,554 shares of our common stock outstanding as of February 28, 2022. Shares underlying options or other rights to acquire our common stock that are exercisable within 60 days of February 28, 2022 are considered outstanding for the purpose of computing the percentage ownership of the person holding such options or other rights, but are not deemed outstanding for computing the percentage ownership of any other persons. The address of all directors and executive officers is c/o Navidea Biopharmaceuticals, Inc., 4995 Bradenton Avenue, Suite 240, Dublin, OH 43017.

All of our employees and directors, or any of their designees, are prohibited from (i) purchasing financial instruments (including prepaid variable forward contracts, equity swaps, collars, and exchange funds), or (ii) otherwise engaging in transactions (including “short sales” and arrangements involving a non-recourse pledge of securities), that hedge or offset, or are designed to hedge or offset, any decrease in the market value of shares of our common stock granted to such employee or director, or any of their designees, as part of their compensation, or held (directly or indirectly) by such employee or director, or any of their designees.

Item 13. Certain Relationships and Related Transactions, and Director Independence

We adhere to our Code of Business Conduct and Ethics, which states that no director, officer or employee of Navidea should have any personal interest that is incompatible with the loyalty and responsibility owed to our Company. We adopted a written policy regarding related party transactions in December 2015. When considering whether to enter into or ratify a related party transaction, the Audit Committee considers a variety of factors including, but not limited to, the nature and type of the proposed transaction, the potential value of the proposed transaction, the impact on the actual or perceived independence of the related party and the potential value to the Company of entering into such a transaction. All proposed transactions with a potential value of greater than $120,000 must be approved or ratified by the Audit Committee.

SEC disclosure rules regarding transactions with related persons require the Company to provide information about transactions with directors and executive officers as a related persons, even though they may not have been related persons at the time the Company entered into the transactions described below.

Dr. Michael Goldberg, our former President and Chief Executive Officer, previously managed a portfolio of funds for Platinum-Montaur Life Sciences LLC (“Platinum-Montaur”), an affiliate of Platinum Management (NY) LLC, Platinum Partners Value Arbitrage Fund L.P. (“PPVA”), Platinum Partners Capital Opportunity Fund (“PPCO”), Platinum Partners Liquid Opportunity Master Fund L.P., Platinum Liquid Opportunity Management (NY) LLC, and Montsant Partners LLC (collectively, “Platinum”), from May 2007 until December 2013. In 2011, he made an initial investment of $1.5 million in PPVA as a passive investor. Dr. Goldberg believes his current investment balance is approximately $1.4 million after giving effect to prior redemptions and reinvestments. Dr. Goldberg was not a member of the management of any of the Platinum entities; rather he solely had control over the trading activities of a portfolio of health care investments from funds allocated to him from the Platinum funds. Dr. Goldberg was responsible for all investments made by Platinum in the Company and for the trading in the Company’s securities up until he joined the Company’s Board of Directors in November 2013, at which time he relinquished all control over the trading of the Company’s securities held by all of the Platinum entities. On December 13, 2013, Dr. Goldberg formally separated from Platinum and had no further role in managing their health care portfolio. As part of his separation from Platinum, Dr. Goldberg entered into a settlement agreement, dated March 28, 2014, and amended on June 11, 2015, with PPVA pursuant to which Dr. Goldberg was entitled to receive a beneficial ownership interest in 15% of (1) all securities held by Platinum at the time of his separation from Platinum which included, without limitation, warrants to purchase the Company’s Common Stock, and (2) the drawn amounts from the Platinum debt facility. In furtherance of the foregoing, on October 17, 2016, Platinum transferred warrants to acquire an aggregate of 5,411,850 shares of our Common Stock to Dr. Goldberg, which warrants were exercised in full by Dr. Goldberg on January 17, 2017 resulting in gross proceeds to the Company of $54,119.

In ~~connection with the closing of the Asset Sale to Cardinal Health 414,~~March 2017, the Company repaid to ~~Platinum Partners Capital Opportunity Fund L.P. (“PPCO”)~~PPCO an aggregate of approximately $7.7 million in ~~partial~~full satisfaction of the Company’s liabilities, obligations and indebtedness under the Platinum Loan Agreement between the Company and Platinum-Montaur, which were transferred by Platinum-Montaur to ~~PPCO.~~

~~On November 2, 2017, Platinum-Montaur~~PPCO (the “Platinum Debt”). Subsequently, competing claims were made by Dr. Goldberg and by PPVA to the unpaid portion of the Platinum Debt. Platinum commenced ~~an action~~litigation against the Company in the Supreme Court of the State of New York, County of New York, seeking damages of approximately $1.9 million purportedly due as of March 3, 2017, plus interest accruing thereafter. The claims asserted were for breach of contractNovember 2017. Platinum and ~~unjust enrichment in connection with funds received by~~ the Company ~~under the Platinum Loan Agreement. The action~~settled their dispute and Platinum’s lawsuit was removed to the United States District Court for the Southern District of New York (the “District Court”) on December 6, 2017. An initial pretrial conference was held on January 26, 2018 and a follow up status conference was held on March 9, 2018, during which the District Court set a briefing schedule and determined that Navidea’s motion to dismiss was due on April 6, 2018. The Company filed its motion to dismissdismissed in advance of the filing deadline. On October 31, 2018, the District Court granted judgment for Navidea and dismissed all claims in the case. The District Court stated that Platinum-Montaur had no standing to assert any contractual interest in funds that might be due under the Platinum Loan Agreement. The District Court also disagreed with Platinum-Montaur’s claim of unjust enrichment on similar grounds and found that Platinum-Montaur lacked any sufficient personal stake to maintain claims against Navidea. The claims against Navidea were dismissed without prejudice on the grounds of lack of standing to pursue the claims asserted.February 2022.

On November 30, 2018, Platinum-Montaur filed a notice of appeal with the United States Court of Appeals for the Second Circuit (the “Second Circuit”) claiming that the District Court erred in dismissing Platinum-Montaur’s claims for breach of contractGoldberg Agreement and unjust enrichment. On January 22, 2019, Platinum-Montaur filed its brief in the Second Circuit, asking the Second Circuit to reverse the District Court and remand the case to the District Court for further proceedings. On February 26, 2019, the Company filed its brief in the Second Circuit. It is not known at this time whether the Second Circuit will hold oral argument on this matter or when the Second Circuit will render its decision.Litigation

~~Effective~~In August ~~14,~~ 2018, Dr. ~~Michael~~ Goldberg resigned from his positions as an executive officer and a director of Navidea. In connection with Dr. Goldberg’s resignation, Navidea and Dr. Goldberg entered into ~~the~~an Agreement ~~with the intent of entering into one or more additional Definitive Agreements,~~(the “Goldberg Agreement”) which set forth the terms of ~~his~~the separation from service. ~~The~~Among other things, the Goldberg Agreement ~~provides~~provided that Dr. Goldberg ~~will~~would be entitled to receive a severance of $978,000 payable in equal installments over two years, along with a one-time payment of approximately $35,000 which represents the cost of continuing his existing health care coverage for a period of 16 months. The Agreement also provides that Dr. Goldberg will be entitled to 23.5 million1,175,000 shares of ~~common stock of Navidea,~~our Common Stock, representing in part payment of accrued bonuses and payment of the balance of the Platinum ~~Note.~~debt. A portion of the ~~23.5 million~~1,175,000 shares to be issued to Dr. Goldberg ~~will~~would be held in escrow for up to 18 months in order to reimburse Navidea in the event that Navidea is obligated to pay any portion of the Platinum ~~Note~~debt to a party other than Dr. Goldberg. Further, the Goldberg Agreement ~~provides~~provided that the Company’s subsidiary, ~~MT, will~~Macrophage Therapeutics, Inc. (“MT”), would redeem all of Dr. Goldberg’s preferred stock and issue to Dr. Goldberg super voting common stock equal to 5% of the outstanding shares of MT. OnIn November ~~20,~~ 2018, the Company issued ~~18.5 million~~925,000 shares of ~~common stock of Navidea~~our Common Stock to Dr. Goldberg, ~~5 million~~250,000 of which were placed in escrow in accordance with the Goldberg Agreement. As

On February 11, 2019, Dr. Goldberg represented to the MT Board that he had, without MT Board or shareholder approval, created a subsidiary of MT, transferred all of the ~~date~~assets of ~~filing~~MT into the subsidiary, and then issued himself stock in the subsidiary. On February 19, 2019, Navidea notified MT that it was terminating the sublicense in accordance with its terms, effective March 1, 2019, due to MT’s insolvency. On February 20, 2019, the MT Board removed Dr. Goldberg as President and Chief Executive Officer of ~~this Annual Report on Form 10-K,~~MT and from any other office of MT to which he may have been appointed or in which he was serving. Dr. Goldberg remains a member of the ~~Definitive Agreements have not yet been signed.~~MT Board, together with John K. Scott, Jr. and Dr. Michael S. Rosol. Mr. Scott is also the Vice Chair of the Board of Directors of Navidea. On or about February 17, 2022, the Joint Official Liquidators and Foreign Representatives of PPVA executed the necessary paperwork to transfer its preferred stock in MT to Navidea.

On February 20, 2019, Navidea filed a complaint against Dr. Goldberg in the United States District Court, ~~for the~~ Southern District of New York, alleging breach of the Goldberg Agreement, as well as a breach of the covenant of good faith and fair dealing and to obtain a declaratory judgment that Navidea’s performance under the Goldberg Agreement is excused and that Navidea is entitled to terminate the Goldberg Agreement as a result of Dr. Goldberg’s actions. On April 26, 2019, Navidea filed an amended complaint against Dr. Goldberg which added a claim for breach of fiduciary duty seeking damages related to certain actions Dr. Goldberg took while CEO of Navidea. On June 13, 2019, Dr. Goldberg answered the amended complaint and asserted counterclaims against Navidea and third-party claims against MT for breach of the Goldberg Agreement, wrongful termination, injunctive relief, and quantum meruit.

On December 26, 2019, the District Court ruled on several motions related to Navidea and MT and Dr. Goldberg that substantially limited the claims that Dr. Goldberg can pursue against Navidea and MT. Specifically, the District Court found that certain portions of Dr. Goldberg’s counterclaims against Navidea and third-party claims against MT failed to state a claim upon which relief can be granted. Additionally, the District Court ruled that actions taken by Navidea and MT, including reconstituting the MT board of directors, replacing Dr. Goldberg with Mr. Latkin as Chief Executive Officer of MT, terminating the sublicense between Navidea and MT, terminating certain research projects, and allowing MT intellectual property to revert back to Navidea, were not breaches of the Goldberg Agreement.

The District Court also rejected Dr. Goldberg’s claim for wrongful termination as Chief Executive Officer of MT. In addition, the District Court found that Dr. Goldberg lacked standing to seek injunctive relief to force the removal of Dr. Claudine Bruck and Michael Rice from MT’s Board of Directors, to invalidate all actions taken by the MT Board on or after November 29, 2018 (the date upon which Dr. Bruck and Mr. Rice were appointed by Navidea to the Board of MT), or to reinstate the terminated sublicense between Navidea and MT.

In addition, the District Court found Navidea’s breach of fiduciary duty claim against Dr. Goldberg for conduct occurring more than three years prior to the filing of the complaint to be time-barred and that Dr. Goldberg is entitled to an advancement of attorneys’ fees solely with respect to that claim. To avoid further litigation expenses, the Company agreed to indemnify Dr. Goldberg solely with respect to the breach of fiduciary duty claim.

On ~~March 7, 2019,~~January 31, 2020, Goldberg filed a motion for leave to amend his complaint to add back in claims for breach of contract, breach of the implied covenant of good faith and fair dealing, quantum meruit and injunctive relief. On April 1, 2020, the District Court denied Dr. Goldberg’s motion for leave to amend in its entirety.

On January 27, 2020, Dr. Goldberg filed a ~~complaint~~motion seeking additional advancement from Navidea for fees in connection with the New York Action and the Delaware Action. Navidea opposed the motion and the District Court referred the matters to a Magistrate Judge. On July 9, 2020, the Magistrate Judge issued her Report and Recommendation which recommended that: (1) the District Court decline to exercise jurisdiction over Dr. Goldberg’s motion as it pertained to expenses and fees incurred in defense of the Delaware Action; (2) the District Court decline to award any fees to Dr. Goldberg for the breach of fiduciary duty without additional motion practice on the issue; (3) the District Court find that Dr. Goldberg is entitled to advancement of his expenses and fees reasonably incurred in the defense of the remainder of the New York action subject to Dr. Goldberg’s posting of an undertaking; and (4) establish a protocol by which Dr. Goldberg could establish the amounts due for advancement.

On August 24, 2020, in connection with Dr. Goldberg’s motion for advancement, the District Court adopted the Magistrate Judge’s report and recommendation and found that while Dr. Goldberg was not being granted advancement of fees and expenses incurred in connection with either the Delaware Action or the assertion of third-party claims against MT, the Court ruled that Dr. Goldberg was entitled to advancement for the defense of the remaining claims asserted against him by Navidea in the New York action. The Court adopted a protocol by which additional motion practice will occur to determine the appropriate amount of fees to be advanced. Once that decision is made by the Magistrate Judge, subject to review by the District Court, Navidea will need to advance those fees to Dr. Goldberg conditioned upon Dr. Goldberg agreeing to pay those fees back to Navidea if it is determined that he is not entitled to indemnification.

On May 27, 2021, the District Court ordered that: (1) Dr. Goldberg be awarded $14,955 for indemnification for his attorneys’ fees for his defense of the breach of fiduciary duty claim; (2) Dr. Goldberg be advanced $1,237.50 for his attorneys’ fees subject to repayment; (3) Navidea should not be required to indemnify or advance any of the costs sought by Dr. Goldberg; (4) Dr. Goldberg is not entitled to advancement for the prosecution of his counterclaims and third-party claims; (5) Dr. Goldberg’s motion to hold Navidea in contempt be denied; and (6) Navidea should not be required to advance any additional fees or costs unless Dr. Goldberg presents his time records and costs in compliance with the District Court’s orders. The Company has made the payments ordered by the District Court.

On August 6, 2021, the Company moved for reconsideration of its obligations to advance fees in light of the Delaware Court’s decision dated June 23, 2021 (described below). On October 14, 2021, the Magistrate Judge recommended that Navidea’s motion for reconsideration be denied. On March 7, 2022, the District Court adopted the Report and Recommendation in part and permitted Dr. Goldberg to seek advancement for his fees incurred in defense of his claims since September 1, 2020. Dr. Goldberg’s application is due on or before April 8, 2022.

Fact discovery and expert discovery in the New York Action have been completed. The Company has moved to disqualify Dr. Goldberg’s damages expert and briefing in the District Court on that issue will be concluded on April 1, 2022.

On February 20, 2019, MT initiated a suit against Dr. Goldberg in the Court of Chancery of the State of Delaware (the “Delaware Court”), alleging, among other things, breach of fiduciary duty as a director and officer of MT and conversion, and to obtain a declaratory judgment that the transactions Dr. Goldberg caused MT to effect are void. On June 12, 2019, the Delaware Court found that Dr. Goldberg’s actions were not authorized in compliance with the Delaware General Corporate Law. Specifically, the Delaware Court found that Dr. Goldberg’s creation of a new subsidiary of MT and the purported assignment by Dr. Goldberg of MT’s intellectual property to that subsidiary were void. The Delaware Court’s ruling follows the order on May 23, 2019 in the case, in which it found Dr. Goldberg in contempt of its prior order holding Dr. Goldberg responsible for the payment of MT’s fees and costs to cure the damages caused by Dr. Goldberg’s contempt.

On June 23, 2021, the Delaware Court ruled in favor of MT and against Dr. Goldberg, finding that Dr. Goldberg breached his fiduciary duties to MT. Specifically, the Delaware Court ruled: “Dr. Goldberg attempted to take for himself that which belonged to [MT]. In doing so, he breached his duty of loyalty to [MT] stockholders. [MT] was absolutely justified in bringing this action to remedy (in this case undo) the harm caused by Dr. Goldberg’s misconduct.” The Delaware Court disagreed with MT’s arguments regarding damages and, other than awarding nominal damages, declined to award additional relief beyond that which it had previously granted. With respect to MT’s claim for conversion, the Delaware Court found that the claim was not supported because “Dr. Goldberg confirmed that he currently does not own or possess any intellectual property related to either Navidea or [MT]” and that “any IP Dr. Goldberg created while at Navidea or any of its subsidiaries was and remains the property of Navidea and its subsidiaries.” In addition, the Delaware Court denied Dr. Goldberg’s motion to hold MT’s directors and CEO in contempt, denied Dr. Goldberg’s motion to dismiss the lawsuit against him, and granted MT’s motion to dismiss Dr. Goldberg’s petition to remove MT’s board members. On December 9, 2021, Dr. Goldberg was ordered to reimburse MT in the ~~United States District Court for~~amount of $66,796.33 and has paid that amount to MT. Neither party has appealed the ~~Southern District of New York. The Complaint alleges a breach of contract claim against both Navidea~~Delaware Court’s decision and ~~MT for failure to pay to Dr. Goldberg funds allegedly due to him under~~ the Platinum Note. The Complaint further alleges a breach of contract claim against Navidea due to Navidea’s failure to issue 23.5 million shares to Dr. Goldberg, to issue MT Super Voting Common Stock, by removing Dr. Greene from the MT Board of Directors, by appointing Mr. Rice and Dr. BruckDelaware Court’s decisions are now final.

See Note 12 to the ~~MT Board of Directors,~~accompanying consolidated financial statements.

Jed A. Latkin, our former Chief Executive Officer, Chief Operating Officer and Chief Financial Officer, was an independent consultant that served as a portfolio manager from 2011 through 2015 for two entities, namely Precious Capital and West Ventures, each of which were during that time owned and controlled, respectively, by PPVA and PPCO. Mr. Latkin was party to a consulting agreement with each of Precious Capital and West Ventures pursuant to which, as of April 2015, an aggregate of approximately $13 million was owed to him, which amount was never paid and Mr. Latkin has no information as to the current value. Mr. Latkin’s consulting agreements were terminated upon his ceasing to be an independent consultant in April 2015 with such entities. During his consultancy, Mr. Latkin was granted a .5% ownership interest in each of Precious Capital and West Ventures, however, to his knowledge he no longer owns such interests. In addition, PPVA owes Mr. Latkin $350,000 for unpaid consulting fees earned and expenses accrued in 2015 in respect of multiple consulting roles with them. Except as set forth above, Mr. Latkin has no other past or present affiliations with Platinum.

~~Dr. Eric Rowinsky, our former Chairman, was recommended for appointment to the Company’s Board of Directors by Dr. Goldberg at a time when Dr. Goldberg was affiliated with~~Macrophage Therapeutics, Inc. and Platinum and was subsequently elected by the Company’s stockholders to continue to serve as an independent director. At no time has Dr. Rowinsky been affiliated, or in any way related to, any of the Platinum entities. Dr. Rowinsky retired from the Company’s Board of Directors effective March 31, 2018.

In March 2015, MT, our previously wholly-owned subsidiary, entered into a Securities Purchase Agreement to sell up to 50 shares of its Series A Convertible Preferred Stock (“MT Preferred Stock”) and warrants to purchase up to 1,500 common shares of MT (“MT Common Stock”) to Platinum and Dr. ~~Michael~~ Goldberg (collectively, the “MT Investors”) for a purchase price of $50,000 per unit. A unit consisted of one share of MT Preferred Stock and 30 warrants to purchase MT Common Stock. Under the agreement, 40% of the MT Preferred Stock and warrants are committed to be purchased by Dr. Goldberg, and the balance by Platinum. The full 50 shares of MT Preferred Stock and warrants to be sold under the agreement are convertible into, and exercisable for, MT Common Stock representing an aggregate 1% interest on a fully converted and exercised basis. Navidea owns the remainder of the MT Common Stock. On March 11, 2015, definitive agreements with the MT Investors were signed for the sale of the first tranche of 10 shares of MT Preferred Stock and warrants to purchase 300 shares of MT Common Stock to the MT Investors, with gross proceeds to MT of $500,000.

~~In addition, we entered into an exchange agreement with the~~ Platinum has since transferred its interests in MT ~~Investors providing them an option~~ to exchange their MT Preferred Stock for our Common Stock in the event that MT has not completed a public offering with gross proceeds to MT of at least $50 million by the second anniversary of the closing of the initial sale of MT Preferred Stock, at an exchange rate per share obtained by dividing $50,000 by the greater of (i) 80% of the twenty-day volume weighted average price per share of our Common Stock on the second anniversary of the initial closing or (ii) $3.00. To the extent that the MT Investors do not timely exercise their exchange right, we have the right to redeem their MT Preferred Stock for a price equal to $58,320 per share.

~~During 2018, the largest aggregate amount of principal outstanding under the Platinum credit facility was $2.2 million, and as of December 31, 2018, the amount of principal outstanding was $0.~~Navidea.

Our Board of Directors has adopted the definition of “independence” as described under the Sarbanes-Oxley Act of 2002 (Sarbanes-Oxley) Section 301, Rule 10A-3 under the Exchange Act and Section 803A of the NYSE American Company Guide. Our Board of Directors has determined that ~~Drs. Bruck~~Messrs. Bhalla, Cappello, Scott and ~~Rouan, and Messrs. Cutler and Rice,~~Witter meet the independence requirements. ~~The Board had also concluded that Drs. Greene and Rowinsky were independent during the time each served as a director until their departure in 2018.~~

Audit Fees. The aggregate fees billed and expected to be billed for professional services rendered by Marcum LLP, primarily related to the audit of the Company’s annual consolidated financial statements for the ~~2018~~2021 fiscal year, ~~and~~ the reviews of the financial statements included in the Company’s Quarterly Reports on Form 10-Q for the ~~2018~~2021 fiscal year, and review of other SEC filings, were ~~$275,850~~$298,650 (including direct engagement expenses).

The aggregate fees ~~billed and expected to be~~ billed for professional services rendered by Marcum LLP, primarily related to the audit of the Company’s annual consolidated financial statements for the ~~2017~~2020 fiscal year, ~~the audit of the Company’s internal control over financial reporting as of December 31, 2017, and~~ the reviews of the financial statements included in the Company’s Quarterly Reports on Form 10-Q for the ~~2017~~2020 fiscal year, and review of other SEC filings, were ~~$342,160~~$294,251 (including direct engagement expenses).

Audit-Related Fees. No fees were billed by Marcum LLP for audit-related services for the ~~2018~~2021 or ~~2017~~2020 fiscal years.

Tax Fees. No fees were billed by Marcum LLP for tax-related services for the ~~2018~~2021 or ~~2017~~2020 fiscal years.

All Other Fees. No fees were billed by Marcum LLP for services other than the audit, audit-related and tax services for the ~~2018~~2021 or ~~2017~~2020 fiscal years.

Pre-Approval Policy. The Audit Committee is required to pre-approve all auditing services and permitted non-audit services (including the fees and terms thereof) to be performed for the Company by its independent auditor or other registered public accounting firm, subject to the de minimis exceptions for permitted non-audit services described in Section 10A(i)(1)(B) of the Exchange Act that are approved by the Audit Committee prior to completion of the audit. The Audit Committee, through the function of the Chairman, has given general pre-approval for 100% of specified audit, audit-related, tax and other services.

Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

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 registrant and in the capacities and on the dates indicated.

We have audited the accompanying consolidated balance sheets of Navidea Biopharmaceuticals, Inc. (the “Company”) as of December 31, ~~2018~~2021 and ~~2017,~~2020, the related consolidated statements of operations, ~~comprehensive (loss) income,~~ stockholders’ ~~(deficit)~~ equity and cash flows for each of the two years in the period ended December 31, ~~2018,~~2021, and the related notes (collectively referred to as 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, ~~2018~~2021 and ~~2017,~~2020, and the results of its operations and its cash flows for each of the two years in the period ended December 31, ~~2018,~~2021, in conformity with accounting principles generally accepted in the United States of America.

The accompanying consolidated financial statements have been prepared assuming that the Company will continue as a going concern. As more fully described in Note 2, the Company has minimal working capital, has incurred significant losses and needs to raise additional funds to meet its obligations and sustain its operations. These conditions raise substantial doubt about the Company's ability to continue as a going concern. Management's plans in regard to these matters are also described in Note 2. The consolidated financial statements do not include any adjustments that might result from the outcome of this uncertainty.

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 Public Company Accounting Oversight Board (United States) ~~(“PCAOB”~~("PCAOB") and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audits to obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits we are required to obtain an understanding of internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company's internal control over financial reporting. Accordingly, we express no such opinion.

Our audits included performing procedures to assess the risks of material misstatement of the 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.

The critical audit matter communicated below is a matter arising from the current period audit of the financial statements that were communicated or required to be communicated to the audit committee and that: (1) relate 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.

Equity Award Modifications – Refer to Note 16 to the consolidated financial statements

The Company entered into a Separation Agreement and General Release (“Separation Agreement”) with Mr. Jed Latkin, the former Chief Executive, Chief Financial, Chief Operation Officer and director on November 23, 2021. Pursuant to the Separation Agreement, among other things, the Company agreed to provide Mr. Latkin with certain separation benefits, commencing on the “Effective Date,” defined as the eighth day after Mr. Latkin signs, without revoking, the Separation Agreement. Pursuant to the terms of the Separation Agreement, on the effective date each of Mr. Latkin’s unvested stock options vested, and all of his vested stock options and previously unvested options may be exercised by Mr. Latkin on or before the earlier of the fifth anniversary of the Separation Date and the original expiration date. On the Effective Date, each of Mr. Latkin’s outstanding unvested restricted stock units became fully vested, and all of such restricted stock units were settled within thirty days after the Separation Date, less applicable withholding in shares of common stock. The modifications to the outstanding equity awards required significant judgement by management related to the assessment of the accounting treatment for the modifications and also the fair value assessments of the equity modification prior to modification and subsequent to modification.

The Company considered various factors, including the fair value of the equity awards immediately prior to modification and immediately after modification and relevant interpretation of the authoritative guidance to determine the incremental fair value incurred relating to the modification.

We identified these equity award modifications as a critical audit matter because evaluating the authoritative guidance and estimating the incremental expense involved significant judgement by management related to the fair values immediately prior and following the modification. This required a high degree of auditor judgment and an increased extent of effort when performing audit procedures to evaluate the Company’s interpretation of the authoritative guidance and assessing the inputs utilized by management to assess the fair value of the equity awards.

Our audit procedures related to the equity award modifications include the following, among others:

Consolidated Statements of ~~Comprehensive~~ ~~(Loss)~~ ~~Income~~Cash Flows

~~Consolidated Statements of Stockholders’~~ ~~(Deficit)~~ ~~Equity~~

1.	Organization and Summary of Significant Accounting Policies

Organization and Nature of Operations: Navidea Biopharmaceuticals, Inc. (“Navidea,” the “Company,” or “we”), a Delaware Corporation (NYSE American: NAVB), is a biopharmaceutical company focused on the development and commercialization of precision immunodiagnostic agents and immunotherapeutics. Navidea is developing multiple precision-targeted products based on our Manocept™ platform to enhance patient care by identifying the sites and pathways of undetected disease and enable better diagnostic accuracy, clinical decision-making and targeted treatment.

Navidea’s Manocept platform is predicated on the ability to specifically target the CD206 mannose receptor expressed on activated macrophages. The Manocept platform serves as the molecular backbone of Tc99m tilmanocept, the first product developed and commercialized by Navidea based on the platform. Other than Tc99m tilmanocept, which the Company has a license to distribute outside of Canada, Mexico and the United States, none of the Company’s drug product candidates have been approved for sale in any market.

In July 2011, we established a British business unit, Navidea Biopharmaceuticals Limited (“Navidea UK”), to address European and international development and commercialization needs for our technologies, including Tc99m tilmanocept. Navidea owns 100% of ~~precision immunodiagnostic agents and immunotherapeutics.~~the outstanding shares of Navidea is developing multiple precision-targeted products based on our Manocept™ platform to enhance patient care by identifying the sites and pathways of undetected disease and enable better diagnostic accuracy, clinical decision-making and targeted treatment.UK.

In January 2015, Macrophage Therapeutics, Inc. (“MT”) was formed specifically to explore immuno-therapeutic applications for the Manocept platform. Navidea owns 99.9% of the outstanding shares of MT.

In June 2020, in anticipation of the United Kingdom’s separation from the European Union (“Brexit”), we established an Irish entity, Navidea Biopharmaceuticals Europe Limited (“Navidea Europe”). Following Brexit, Navidea Europe allows us to continue to develop and commercialize our technologies within the European Union (“EU”) as well as internationally. Navidea owns 100% of the outstanding shares of Navidea Europe.

On March 3, 2017, pursuant to an Asset Purchase Agreement dated November 23, 2016, the Company completed its previously announced sale to Cardinal Health 414 of its assets used, held for use, or intended to be used in operating its business of developing, manufacturing and commercializing a product used for lymphatic mapping, lymph node biopsy, and the diagnosis of metastatic spread to lymph nodes for staging of cancer, including the Company’s radioactive diagnostic agent marketed under the Lymphoseek^® trademark for current approved indications by the FDA and similar indications approved by the FDA in the future, in Canada, Mexico and the United States (giving effect to the License-Back described below and excluding certain assets specifically retained by the Company). Such assets sold in the Asset Sale consist primarily of, without limitation, (i) intellectual property used in or reasonably necessary for the conduct of the Business, (ii) inventory of, and customer, distribution, and product manufacturing agreements related to, the Business, (iii) all product registrations related to the Product, including the new drug application approved by the FDA for the Product and all regulatory submissions in the United States that have been made with respect to the Product and all Health Canada regulatory submissions and, in each case, all files and records related thereto, (iv) all related clinical trials and clinical trial authorizations and all files and records related thereto, and (v) all right, title and interest in and to the Product, as specified in the Purchase Agreement. Upon closing of the Asset Sale, the Supply and Distribution Agreement, dated November 15, 2007, as amended, between Cardinal Health 414 and the Company was terminated and, as a result, the provisions thereof are of no further force or effect.

~~In January 2015, MT, a majority-owned subsidiary, was formed specifically to explore immuno-therapeutic applications for the Manocept platform.~~

In July 2011, we established a European business unit, Navidea Biopharmaceuticals Limited, to address international development and commercialization needs for our technologies, including Tc99m tilmanocept. Navidea owns 100% of the outstanding shares of Navidea Biopharmaceuticals Limited.

In December 2001, we acquired Cardiosonix Ltd. (“Cardiosonix”), an Israeli company with a blood flow measurement device product line in the early stages of commercialization. In August 2009, the Company’s Board of Directors decided to discontinue the operations and attempt to sell Cardiosonix. However, we were obligated to continue to service and support the Cardiosonix devices through 2013. The Company did not receive significant expressions of interest in the Cardiosonix business and it was legally dissolved in September 2017.

Principles of Consolidation: Our consolidated financial statements include the accounts of Navidea and our wholly-owned subsidiaries, Navidea ~~Biopharmaceuticals Limited~~Europe and ~~Cardiosonix Ltd,~~Navidea UK, as well as those of our majority-owned subsidiary, MT. All significant inter-company accounts were eliminated in consolidation.

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 reported amounts of assets and liabilities and disclosure of contingent assets and liabilities at the date of the financial statements and the reported amounts of ~~assets and liabilities and disclosure of contingent assets and liabilities at the date of the financial statements and the reported amounts of~~ revenues and expenses during the reporting period. Actual results could differ from those estimates.

~~Financial Instruments~~Revenue Recognition: We currently generate revenue from a grant to support one of our product development initiatives. We generally recognize grant revenue when expenses reimbursable under the grant have been paid and ~~Fair Value:~~ Inpayments under the grant become contractually due.

We also earn revenues related to our licensing and distribution agreements. The consideration we are eligible to receive under our licensing and distribution agreements typically includes upfront payments, reimbursement for research and development (“R&D”) costs, milestone payments, and royalties. Each licensing and distribution agreement is unique and requires separate assessment in accordance with current accounting standards, the fair value hierarchy prioritizes the inputs to valuation techniques used to measure fair value, giving the highest priority to unadjusted quoted prices in active markets for identical assets or liabilities (Level 1 measurements) and the lowest priority to unobservable inputs (Level 3 measurements). The three levels of the fair value hierarchy are described below:standards. See Note 3.

~~Level 1~~ ~~– Unadjusted quoted prices in active markets that are accessible at the measurement date for identical, unrestricted assets or liabilities;~~

~~Level 2~~ ~~– Quoted prices in markets that are not active or financial instruments for which all significant inputs are observable, either directly or indirectly; and~~

~~Level 3~~ ~~– Prices or valuations that require inputs that are both significant to the fair value measurement and unobservable.~~

A financial instrument’s level within the fair value hierarchy is based on the lowest level of any input that is significant to the fair value measurement. In determining the appropriate levels, we perform a detailed analysis of the assets and liabilities whose fair value is measured on a recurring basis. At each reporting period, all assets and liabilities for which the fair value measurement is based on significant unobservable inputs or instruments which trade infrequently and therefore have little or no price transparency are classified as Level 3. See Note 5.

~~The following methods and assumptions were used to estimate the fair value of each class of financial instruments:~~

~~(1)~~

~~Cash~~ ~~and cash equivalents~~, ~~available-for-sale securities,~~ ~~accounts and other receivables,~~ ~~and~~ ~~accounts payable:~~ ~~The carrying amounts approximate fair value because of the short maturity of these instruments.~~

~~(2)~~

~~Notes payable:~~ The carrying value of our debt at December 31, 2018 and 2017 primarily consisted of the face amount of the notes plus accrued interest. At December 31, 2018, the fair value of our notes payable was approximately $316,000, equal to the carrying value of $316,000. At December 31, 2017, the fair value of our notes payable was approximately $2.4 million, equal to the carrying value of $2.4 million. See Notes 5 and 12.

~~(3)~~

~~Derivative liabilities:~~ Derivative liabilities are related to certain outstanding warrants which are recorded at fair value. Derivative liabilities totaling $63,000 as of December 31, 2018 and 2017 were included in other liabilities on the consolidated balance sheets. The assumptions used to calculate fair value as of December 31, 2018 and 2017 included volatility, a risk-free rate and expected dividends. In addition, we considered non-performance risk and determined that such risk is minimal. Unrealized gains and losses on the derivatives are classified in other expenses as a change in the fair value of financial instruments in the statements of operations. See Note 5.

~~(4)~~

~~Warrants:~~ In March 2017, in connection with the Asset Sale, the Company granted to each of Cardinal Health 414 and UCSD, a five-year warrant to purchase up to 10 million shares and 1 million shares, respectively, of the Company’s common stock at an exercise price of $1.50 per share, each of which warrant is subject to anti-dilution and other customary terms and conditions (the “Series NN warrants”). The assumptions used to calculate fair value at the date of issuance included volatility, a risk-free rate and expected dividends. The Series NN warrants granted to Cardinal Health 414 had an estimated fair value of $3.3 million, which was recorded as a reduction of the gain on sale in the consolidated statement of operations for the year ended December 31, 2017. The Series NN warrants granted to UCSD had an estimated fair value of $334,000, which was recorded as an intangible asset related to the UCSD license in the consolidated balance sheet at the time of issuance. See Note 16(b).

Stock-Based Compensation: At As of December 31, ~~2018,~~ 2021, we had instruments outstanding under two stock-based compensation plans; the Fourth Amended and Restated 2002 Stock Incentive Plan (the ~~“2002~~“2002 Plan”) and the Amended and Restated 2014 Stock Incentive Plan (the ~~“2014~~“2014 Plan”). Currently, under the 2014 Plan, we may grant incentive stock options, nonqualified stock options, and restricted stock awards to full-time employees and directors, and nonqualified stock options and restricted stock awards may be granted to our consultants and agents. Total shares authorized under ~~each plan are 12 million shares and 15 million shares, respectively.~~the 2014 Plan is 1,750,000 shares. Although instruments are still outstanding under the 2002 Plan, the ~~plan~~2002 Plan has expired and no new grants may be made from it. Under both plans, the exercise price of each option is greater than or equal to the closing market price of our ~~common~~Common Stock on the date of the grant.

Stock options granted under the 2002 Plan and the 2014 Plan generally vest on an annual basis over one to four years. Outstanding stock options under the plans, if not exercised, generally expire ten years from their date of grant or up to 90 days following the date of an optionee’s separation from employment with the Company. We issue new shares of our Common Stock upon exercise of stock options.

Stock-based payments to employees and directors, including grants of stock options and restricted stock, are recognized in the statements of operations based on their estimated fair values on the date of grant, subject to an estimated forfeiture rate. The fair value of each option award with time-based vesting provisions is estimated on the date of grant using the Black-Scholes option pricing model. The determination of fair value using the Black-Scholes option pricing model is affected by our stock price as well as assumptions regarding a number of complex and subjective variables, including expected stock price volatility, risk-free interest rate, expected dividends and projected employee stock option behaviors. The fair value of each option award with market-based vesting provisions is estimated on the date of grant using a Monte Carlo simulation. The determination of fair value using a Monte Carlo simulation is affected by our stock price as well as assumptions regarding a number of complex and subjective variables, including expected stock price volatility, risk-free interest rate, expected dividends and projected employee stock option behaviors.

F- 9

Expected volatilities are based on the Company’s historical volatility, which management believes represents the most accurate basis for estimating expected future volatility under the current circumstances. Navidea uses historical data to estimate forfeiture rates. The expected term of stock options granted is based on the vesting period and the contractual life of the options. The risk-free rate is based on the U.S. Treasury yield in effect at the time of the grant. The assumptions used to calculate the fair value of stock option awards granted during the years ended December 31, 2021 and 2020 are noted in the following table.

	2021			2020
Expected volatility	90%	-	102%	86%	-	102%
Weighted-average volatility		95%			92%
Expected forfeiture rate	5.2%	-	9.0%	7.0%	-	10.5%
Expected term (in years)	5.5	-	6.2	5.5	-	6.0
Risk-free rate	0.6%	-	1.4%	0.4%	-	1.5%
Expected dividends		0			0

The portion of the fair value of stock-based awards that is ultimately expected to vest is recognized as compensation expense over either (1) the requisite service period or (2) the estimated performance period. Restricted stock awards are valued based on the closing stock price on the date of grant and amortized ratably over the estimated life of the award. Restricted stock may vest based on the passage of time, or upon occurrence of a specific event or achievement of goals as defined in the grant agreements. In such cases, we record compensation expense related to grants of restricted stock based on management’s estimates of the probable dates of the vesting events. Stock-based awards that do not vest because the requisite service period is not met prior to termination result in reversal of previously recognized compensation cost. See Note 4.

Stock options granted under the 2002 Plan and the 2014 Plan generally vest on an annual basis over one to four years. Outstanding stock options under the plans, if not exercised, generally expire ten years from their date of grant or up to 90 days following the date of an optionee’s separation from employment with the Company. We issue new shares of our common stock upon exercise of stock options.

Stock-based payments to employees and directors, including grants of stock options, are recognized in the consolidated statement of operations based on their estimated fair values. The fair value of each stock option award is estimated on the date of grant using the Black-Scholes option pricing model. Expected volatilities are based on the Company’s historical volatility, which management believes represents the most accurate basis for estimating expected future volatility under the current circumstances. Navidea uses historical data to estimate forfeiture rates. The expected term of stock options granted is based on the vesting period and the contractual life of the options. The risk-free rate is based on the U.S. Treasury yield in effect at the time of the grant. The assumptions used to calculate the fair value of stock option awards granted during the years ended December 31, 2018 and 2017 are noted in the following table:

2018

2017

Expected volatility
64% - 76% 66% - 79%
Weighted-average volatility
69% 75%
Expected dividends
— —
Expected term (in years)
5.5 - 6.0 5.0 - 6.0
Risk-free rate
2.6% - 2.7% 1.8% - 2.1%

The portion of the fair value of stock-based awards that is ultimately expected to vest is recognized as compensation expense over either (1) the requisite service period or (2) the estimated performance period. Restricted stock awards are valued based on the closing stock price on the date of grant and amortized ratably over the estimated life of the award. Restricted stock may vest based on the passage of time, or upon occurrence of a specific event or achievement of goals as defined in the grant agreements. In such cases, we record compensation expense related to grants of restricted stock based on management’s estimates of the probable dates of the vesting events. Stock-based awards that do not vest because the requisite service period is not met prior to termination result in reversal of previously recognized compensation cost. See Note 6.

~~Cash~~Research and ~~Cash Equivalents:~~Development Costs: ~~Cash equivalents~~R&D expenses include both internal R&D activities and external contracted services. Internal R&D activity expenses include salaries, benefits, and stock-based compensation, as well as travel, supplies, and other costs to support our R&D staff. External contracted services include clinical trial activities, manufacturing and control-related activities, and regulatory costs. R&D expenses are ~~highly liquid instruments such~~charged to operations as ~~U.S. Treasury bills, bank certificates~~incurred. We review and accrue R&D expenses based on services performed and rely upon estimates of ~~deposit, corporate commercial paper and money market funds which have maturities~~those costs applicable to the stage of ~~less than three months from the date~~completion of ~~purchase.~~each project.

~~Available-for-Sale Securities:~~ Available-for-sale securities are liquid instruments such as U.S. Treasury bills, bank certificates of deposit, corporate commercial paper and money market funds which have maturities of three months or more from the date of purchase.

~~Accounts~~ Stock Subscriptions and Other ~~Receivable~~s:Receivables: ~~Accounts~~Stock subscriptions and other receivables are recorded net of an allowance for doubtful accounts. We estimate an allowance for doubtful accounts based on a review and assessment of specific accounts and other receivables and write off accounts against the allowance account when deemed uncollectible. See Note 8.6.

i.h.

~~Property and Equipment:~~Inventory: ~~Property and equipment~~All components of inventory are ~~stated~~valued at the lower of cost ~~less accumulated depreciation and amortization. Depreciation~~(first-in, first-out) or net realizable value. We adjust inventory to net realizable value when the net realizable value is ~~generally computed using~~lower than the ~~straight-line method over the estimated useful lives~~carrying cost of the ~~depreciable assets. Depreciation~~inventory. Net realizable value is determined based on estimated sales activity and ~~amortization related to equipment under capital leases~~margins. We estimate a reserve for obsolete inventory based on management’s judgment of probable future commercial use, which is based on an analysis of current inventory levels, estimated future sales and ~~leasehold improvements is recognized over the shorter of the~~production rates, and estimated ~~useful life of the leased asset or the term of the lease. Maintenance and repairs are charged to expense as incurred, while renewals and improvements are capitalized.~~shelf lives. See Note 9.7.

j.i.

Intangible Assets: Intangible assets consist primarily of license ~~agreements.~~agreements, and patent and trademark costs. Intangible assets are stated at cost, less accumulated amortization. License agreements and patent costs are amortized using the straight-line method over the estimated useful lives of the license agreements and patents of approximately 5 to 15 years. Patent application costs are deferred pending the outcome of patent applications. Costs associated with unsuccessful patent applications and abandoned intellectual property are expensed when determined to have no recoverable value. We evaluate the potential alternative uses of all intangible assets, as well as the recoverability of the carrying values of intangible assets, on a recurring basis. During 2021 and 2020, we capitalized patent and trademark costs of $304,000 and $278,000, respectively. During 2021 and 2020, we abandoned patents with previously-capitalized patent costs of $99,000 and $9,000, respectively.

~~Impairment or Disposal of Long-Lived Assets:~~ Long-lived assets and certain identifiable intangibles are reviewed for impairment whenever events or changes in circumstances indicate that the carrying amount of an asset 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 future undiscounted cash flows expected to be generated by the asset. If such assets are considered to be impaired, the impairment recognized is measured by the amount by which the carrying amount of the assets exceeds the fair value of the assets. No impairment was recognized during the years ended December 31, 2018 or 2017. Assets to be disposed of are reported at the lower of the carrying amount or fair value less costs to sell.

l.j.

Leases: ~~Leases~~All of our leases are ~~categorized~~operating leases and are included in right-of-use lease assets, current lease liabilities and noncurrent lease liabilities on our consolidated balance sheets. These assets and liabilities are recognized at the commencement date based on the present value of remaining lease payments over the lease term using the Company’s incremental borrowing rates or implicit rates, when readily determinable. The discount rates used for each lease were based principally on the Platinum debt, which was secured and outstanding for most of 2018. We used a “build-up” method where the approach was to estimate the risk/credit spread priced into the debt rate and then adjust that for the remaining term of each lease. Additionally, some market research was completed on the Company’s peer group as ~~either~~identified for purposes of compensation analysis. Short-term operating leases which have an initial term of 12 months or ~~capital~~less are not recorded on the consolidated balance sheets. Lease expense for operating leases ~~at inception. Operating lease costs are~~is recognized on a straight-line basis over the ~~term~~lease term. Lease expense is included in selling, general and administrative expenses on our consolidated statements of ~~the lease. An asset and a corresponding liability for the capital lease obligation are established for the cost of capital leases. The capital lease obligation is amortized over the life of the lease.~~operations. See Note ~~14.~~11.

F- 10

m.k.

~~Derivative Instruments:~~Contingent Liabilities: ~~Derivative instruments~~We are subject to legal proceedings and claims that arise in the normal course of business. In accordance with ASC Topic 450,Contingencies, we accrue for contingent liabilities when management determines it is probable that a liability has been incurred and the amount can be reasonably estimated. This determination requires significant judgment by management. As of the date of the filing of this Annual Report on Form 10-K, we are engaged in separate matters of ongoing litigation with Capital Royalty Partners II, L.P. and our former President and Chief Executive Officer, Dr. Michael Goldberg.

In assessing whether we should accrue a liability in our financial statements as a result of the lawsuits, we considered various factors, including the legal and factual circumstances of the cases, the trial records and post-trial rulings of the applicable courts and appellate courts, the current status of the proceedings, applicable law and the views of legal counsel. We have concluded that a loss from these cases is not probable and reasonably estimable and, therefore, a liability has not been recorded with respect to these cases as of December 31, 2021. While we believe that the ultimate resolution of these matters will not have a material impact on our financial statements, the outcome of litigation is inherently uncertain and the final resolution of these matters may result in expense to us in excess of management's expectations. See Note 12.

Convertible Preferred Stock: The Company evaluated the provisions of the Series C, Series D and Series E Convertible Preferred Stock under Accounting Standards Codification (“ASC”) 480,Distinguishing Liabilities from Equity, ASC 815,Derivatives and Hedging, ASC 470,Debt, and Accounting Series Release (“ASR”) 268,Presentation in Financial Statements of “Redeemable Preferred Stocks.” Based on this evaluation, the Company determined that neither the Series C, Series D nor Series E Preferred Stock is a mandatorily redeemable financial instrument and any obligation to issue a variable number of shares of Common Stock is not unconditional. Accordingly, the Series C, Series D and Series E Preferred Stock should be classified as equity. Neither the embedded ~~in contracts,~~conversion option nor the embedded call option meet the criteria to ~~the extent not already a free-standing contract, are bifurcated~~be separated from the ~~debt instrument~~Series C, Series D or Series E Preferred stock and thus these features should not be bifurcated and accounted for ~~separately. All derivatives are recorded~~as derivatives. Additionally, the Series C and Series D Preferred Stock contain a beneficial conversion feature (“BCF”). Prior to the adoption of Accounting Standards Update (“ASU”) No.2020-06,Accounting for Convertible Instruments and Contracts in an Entity’s Own Equity, effective January 1, 2021, the BCF resulted in an increase to additional paid-in capital and a discount on the Series C and Series D Preferred Stock. The discounts on the Series C and Series D Preferred Stock were considered to be fully amortized at the date of issuance because the Series C and Series D Preferred Stock are immediately convertible, resulting in a deemed dividend at the date of issuance for the amount of the BCF. Following adoption of ASU 2020-06,no BCF is recorded in the consolidated ~~balance sheet at fair value~~financial statements. Finally, the Company determined that the Series D and Series E Preferred Stock does not contain conversion features that could result in ~~accordance with current accounting guidelines for such complex financial instruments. Derivative liabilities with expiration dates within one year are~~the Company being required to redeem a portion of the shares converted, thus the Series D and Series E Preferred Stock should not be classified ~~as current, while those with expiration dates~~ in ~~more than one year are classified as long term. We do not use derivative instruments for hedging of market risks or for trading or speculative purposes.~~mezzanine equity. See Note 13.

~~Revenue Recognition:~~ We currently generate revenue primarily from grants to support various product development initiatives. We generally recognize grant revenue when expenses reimbursable under the grants have been paid and payments under the grants become contractually due.

~~Research and Development Costs:~~ Research and development (“R&D”) expenses include both internal R&D activities and external contracted services. Internal R&D activity expenses include salaries, benefits, and stock-based compensation, as well as travel, supplies, and other costs to support our R&D staff. External contracted services include clinical trial activities, manufacturing and control-related activities, and regulatory costs. R&D expenses are charged to operations as incurred. We review and accrue R&D expenses based on services performed and rely upon estimates of those costs applicable to the stage of completion of each project.

p.m.

Income Taxes: Income taxes are accounted for under the asset and liability method. Deferred tax assets and liabilities are recognized for the future tax consequences attributable to differences between the financial statement carrying amounts of existing assets and liabilities and their respective tax bases, and operating loss and tax credit carryforwards. Deferred tax assets and liabilities are measured using enacted tax rates expected to apply to taxable income in the years in which those temporary differences are expected to be recovered or settled. The effect on deferred tax assets and liabilities of a change in tax rates is recognized in income in the period that includes the enactment date. Due to the uncertainty surrounding the realization of the deferred tax assets in future tax returns, all of the deferred tax assets have been fully offset by a valuation allowance at as of December 31, ~~2018~~ 2021 and ~~2017.~~2020.

Current accounting standards include guidance on the accounting for uncertainty in income taxes recognized in the financial statements. Such standards also prescribe a recognition threshold and measurement model for the financial statement recognition of a tax position taken, or expected to be taken, and provides guidance on derecognition, classification, interest and penalties, accounting in interim periods, disclosure and transition. The Company believes that the ultimate deductibility of all tax positions is highly certain, although there is uncertainty about the timing of such deductibility. As a result, no liability for uncertain tax positions was recorded as of December 31, 2018 or 2017 and we do not expect any significant changes in the next twelve months. Should we need to accrue interest or penalties on uncertain tax positions, we would recognize the interest as interest expense and the penalties as a selling, general and administrative expense. As of December 31, 2018, tax years 2015-2018 remained subject to examination by federal and state tax authorities. See Note 17.

Current accounting standards include guidance on the accounting for uncertainty in income taxes recognized in the financial statements. Such standards also prescribe a recognition threshold and measurement model for the financial statement recognition of a tax position taken, or expected to be taken, and provides guidance on derecognition, classification, interest and penalties, accounting in interim periods, disclosure and transition. The Company believes that the ultimate deductibility of all tax positions is highly certain, although there is uncertainty about the timing of such deductibility. As a result, 0 liability for uncertain tax positions was recorded as of December 31, 2021 or 2020 and we do not expect any significant changes in the next twelve months. Should we need to accrue interest or penalties on uncertain tax positions, we would recognize the interest as interest expense and the penalties as a selling, general and administrative expense. As of December 31, 2021, tax years 2018-2021 remained subject to examination by federal and state tax authorities. See Note 14.

F- 11

Recently Adopted Accounting Standards: In ~~May 2014,~~ August 2018, the Financial Accounting Standards Board (“FASB”) issued ASU ~~2014-09,~~No.2018-13, ~~Revenue from Contracts with Customers~~Fair Value Measurement (Topic ~~606)~~820):~~, which supersedes existing revenue recognition guidance under U.S. GAAP. The core principle~~Disclosure Framework—Changes to the Disclosure Requirements for Fair Value Measurement. ASU 2018-13 is intended to improve the effectiveness of disclosure requirements on fair value measurements in Topic 820.ASU ~~2014-09~~2018-13 modifies certain disclosure requirements and is ~~that a company should recognize revenue when it transfers promised goods or services to customers in an amount that reflects the consideration to which the company expects to be entitled in exchange~~effective for ~~those goods or services. ASU 2014-09 defines a five-step process that requires companies to exercise more judgment~~annual and make more estimates than under the previous guidance. These may include identifying performance obligations in the contract, estimating the amount of variable consideration to include in the transaction price, and allocating the transaction price to each separate performance obligation. Since the issuance of ASU 2014-09, several additional ASUs have been issued and incorporated within Topic 606 to clarify various elements of the guidance. We adopted ASU 2014-09, along with additional related ASUs 2016-08, 2016-10, 2016-12 and 2016-20, effective January 1, 2018, using the modified retrospective method of adoption. interim reporting periods beginning after December 15, 2019. The adoption of ASU ~~2014-09 and related ASUs resulted in increases in deferred revenue and a corresponding offset to accumulated deficit of $700,000. See Note 4.~~2018-13 did not have any impact on our consolidated financial statements or our fair value disclosures.

~~In November 2016, the FASB issued ASU No. 2016-18,~~ ~~Statement of Cash Flows – Restricted Cash~~. ASU 2016-18 requires that the statement of cash flows explain the change during the period in the total of cash, cash equivalents, and restricted cash or equivalents. Therefore, restricted cash and restricted cash equivalents should be included with cash and cash equivalents when reconciling the beginning-of-period and end-of-period total amounts shown on the statement of cash flows. ASU 2016-18 is effective for public business entities for fiscal years beginning after December 15, 2017, and interim periods within those fiscal years. Early adoption is permitted, including adoption in an interim period. If an entity early adopts ASU 2016-18 in an interim period, any adjustments should be reflected as of the beginning of the fiscal year that includes the interim period. We adopted ASU 2016-18 effective January 1, 2018. The adoption of ASU 2016-18 resulted in reclassification of $5.0 million of restricted cash in the consolidated statement of cash flows for the year ended December 31, 2017.

~~In January 2017, the FASB issued ASU No. 2017-01,~~ ~~Business Combinations (Topic 805), Clarifying the Definition of a Business~~. ASU 2017-01 provides a screen to determine when a set of assets and activities (collectively, a “set”) is not a business. The screen requires that when substantially all of the fair market value of the gross assets acquired (or disposed of) is concentrated in a single identifiable asset or a group of similar identifiable assets, the set is not a business. If the screen is not met, ASU 2017-01 (1) requires that to be considered a business, a set must include, at a minimum, an input and a substantive process that together significantly contribute to the ability to create output, and (2) removes the evaluation of whether a market participant could replace missing elements. ASU 2017-01 is effective for public business entities for annual periods beginning after December 15, 2017, including interim periods within those periods. ASU 2017-01 should be applied prospectively on or after the effective date. No disclosures are required at transition. Early adoption is permitted for certain transactions as described in ASU 2017-01. We adopted ASU 2017-01 effective January 1, 2018. The adoption of ASU 2017-01 did not have a material effect on our consolidated financial statements.

~~In May 2017, the FASB issued ASU No. 2017-09,~~ ~~Compensation-Stock Compensation (Topic 718), Scope of Modification Accounting~~. ASU 2017-09 provides guidance about which changes to the terms or conditions of a share-based payment award require an entity to apply modification accounting. An entity should account for the effects of a modification unless all of the following criteria are met: (1) The fair value of the modified award is the same as the fair value of the original award immediately before the original award is modified. If the modification does not affect any of the inputs to the valuation technique that the entity uses to value the award, the entity is not required to estimate the value immediately before and after the modification. (2) The vesting conditions of the modified award are the same as the vesting conditions of the original award immediately before the original award is modified. (3) The classification of the modified award as an equity instrument or a liability instrument is the same as the classification of the original award immediately before the original award is modified. Disclosure requirements remain unchanged. ASU 2017-09 is effective for all entities for annual periods, and interim periods within those annual periods, beginning after December 15, 2017. Early adoption is permitted as described in ASU 2017-09. We adopted ASU 2017-09 effective January 1, 2018. The adoption of ASU 2017-09 did not have a material effect on our consolidated financial statements.

~~In March 2018, the FASB issued ASU No. 2018-05,~~ ~~Income Taxes (Topic 740) – Amendments to SEC Paragraphs Pursuant to SEC Staff Accounting Bulletin No. 118~~. ASU 2018-05 amends Accounting Standards Codification (“ASC”) Topic 740 to provide guidance on accounting for the tax effects of the Tax Cuts and Jobs Act (the “Tax Act”) pursuant to Staff Accounting Bulletin No. 118. ASU 2018-05 addresses situations where the accounting under ASC Topic 740 is incomplete for certain income tax effects of the Tax Act upon issuance of the entity’s financial statements for the reporting period in which the Tax Act was enacted. The adoption of ASU 2018-05 in March 2018 did not have a material effect on our consolidated financial statements.

~~Recent~~~~ly Issued~~ ~~Accounting~~ ~~Standards~~:In ~~February 2016,~~December2019, the FASB issued ASU No. ~~2016-02,~~2019-12, ~~Leases~~Income Taxes (Topic ~~842)~~740): Simplifying the Accounting for Income Taxes. ASU ~~2016-02 requires~~2019-12 is intended to improve consistent application and simplify the ~~recognition~~accounting for income taxes. ASU 2019-12 removes certain exceptions to the general principles in Topic 740 and clarifies and amends existing guidance. ASU 2019-12 is effective for annual and interim reporting periods beginning after December 12, 2020, with early adoption permitted. The adoption of ~~lease assets~~ASU 2019-12 did not have a material impact on our consolidated financial statements.

In August 2020, the FASB issued ASU No.2020-06,Accounting for Convertible Instruments and ~~lease~~Contracts in an Entity’s Own Equity. ASU 2020-06 was issued to reduce the complexity associated with accounting for certain financial instruments with characteristics of liabilities ~~by lessees~~and equity. ASU 2020-06 reduces the number of accounting models for ~~those leases classified as operating leases under previous U.S. GAAP. The core principle of Topic 842 is that a lessee should recognize~~convertible debt instruments and convertible preferred stock and improves the ~~assets~~disclosures for convertible instruments and ~~liabilities that arise from leases. A lessee should recognize in~~related earnings-per-share (“EPS”) guidance. ASU 2020-06 also amends 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~~guidance for the ~~lease term.~~derivatives scope exception for contracts in an entity’s own equity and improves and amends the related EPS guidance. ASU ~~2016-02~~2020-06 is effective for public business entities except smaller reporting companies for annual and interim reporting periods beginning after December 15, 2021, and for annual and interim reporting periods beginning after December 15, 2023 for all other entities. Early adoption is permitted, but the guidance must be adopted as of the beginning of a fiscal year. We adopted ASU 2020-06 effective January 1, 2021 using the modified retrospective method. Prior to the adoption of ASU 2020-06, the BCF contained in the Series C and Series C Preferred Stock resulted in an increase to additional paid-in capital and a discount on the Series C and Series D Preferred Stock. The discounts on the Series C and Series D Preferred Stock were considered to be fully amortized at the date of issuance because the Series C and Series D Preferred Stock are immediately convertible, resulting in a deemed dividend at the date of issuance for the amount of the BCF. Following adoption of ASU 2020-06,no BCF is recorded in the consolidated financial statements. The adoption of ASU 2020-06 did not result in a cumulative effect adjustment to retained earnings.

Recently Issued Accounting Standards: In May 2021, the FASB Issued ASU No.2021-04,Issuer’s Accounting for Certain Modifications or Exchanges of Freestanding Equity-Classified Written Call Options. ASU 2021-04 was issued to clarify and reduce diversity in an issuer’s accounting for modifications or exchange of freestanding equity-classified written call options (for example, warrants) that remain equity-classified after modification or exchange. ASU 2021-04 requires that an entity treat a modification or exchange of a freestanding equity-classified written call option that remains equity-classified after modification or exchange be treated as an exchange of the original instrument for a new instrument. ASU 2021-04 also clarifies how an entity should measure and recognize the effect of a modification or exchange of a freestanding equity-classified written call option that remains equity-classified after modification or exchange. ASU 2021-04 is effective for all entities for fiscal years beginning after December 15, ~~2018,~~ 2021, including interim periods within those fiscal ~~years.~~years, and should be implemented prospectively to modifications or exchanges occurring on or after the effective date of the amendments. Early adoption is ~~permitted.~~permitted, including in an interim period. We ~~have completed our assessment of the impact of adopting ASU 2016-02, and~~do not expect the adoption of ASU ~~2016-02~~2021-04 to result in an increase in right-of-use assets and related liabilities of approximately $286,000 on our balance sheet related to our leases that are currently classified as operating leases, primarily for office space.

~~In June 2018, the FASB issued ASU No. 2018-07,~~ ~~Compensation—Stock Compensation (Topic 718) – Improvements to Nonemployee Share-Based Payment Accounting~~. ASU 2018-07 expands the scope of Topic 718 to include share-based payment transactions for acquiring goods and services from nonemployees. An entity should apply the requirements of Topic 718 to nonemployee awards except for specific guidance on inputs to an option pricing model and the attribution of cost. ASU 2018-07 specifies that Topic 718 applies to all share-based payment transactions in which a grantor acquires goods or services to be used or consumed in a grantor’s own operations by issuing share-based payment awards, and that Topic 718 does not apply to share-based payments used to effectively provide (1) financing to the issuer or (2) awards granted in conjunction with selling goods or services to customers as part of a contract accounted for under Topic 606, ~~Revenue from Contracts with Customers~~. ASU 2018-07 is effective for public business entities for fiscal years beginning after December 15, 2018, including interim periods within that fiscal year. The adoption of ASU 2018-07 is not expected to have a significanthave a material impact on our consolidated financial statements.

In November 2021, the FASB issued ASU No.2021-10,Disclosures by Business Entities about Government Assistance. ASU 2021-10 was issued to increase the transparency of government assistance. ASU 2021-10 requires that entities make certain annual disclosures about transactions with a government that are accounted for by applying a grant or contribution accounting model by analogy. The required disclosures include: (1) information about the nature of the transactions and the related accounting policy used to account for the transactions; (2) the line items on the balance sheet and income statement that are affected by the transactions, and the amounts applicable to each financial statement line item; and (3) significant terms and conditions of the transactions, including commitments and contingencies. The amendments in ASU 2021-10 are effective for all entities within their scope for financial statements issued for annual periods beginning after December 15, 2021. Early application of the amendments is permitted. An entity should apply the amendments in ASU 2021-10 either (1) prospectively to all transactions within the scope of the amendments that are reflected in financial statements at the date of initial application and new transactions that are entered into after the date of initial application or (2) retrospectively to those transactions. We do not expect the adoption of ASU 2021-10 to have an impact on our consolidated financial statements, however we do expect to make the additional disclosures required by the update.

F- 12

Liquidity

The Company has been engaged in litigation with Platinum-Montaur Life Sciences LLC (“Platinum-Montaur”), an affiliate of Platinum Management (NY) LLC, Platinum Partners Value Arbitrage Fund L.P., Platinum Partners Capital Opportunity Fund, Platinum Partners Liquid Opportunity Master Fund L.P., Platinum Liquid Opportunity Management (NY) LLC, and Montsant Partners LLC (collectively, “Platinum”). See Note 12.

In ~~July 2018,~~addition, the ~~FASB issued ASU No. 2018-09,~~ ~~Codification Improvements~~. ASU 2018-09 updates a variety of topics in order to clarify, correct errors, or make minor improvements to the Codification, making it easier to understand and easier to apply by eliminating inconsistencies and providing clarifications. Certain amendments in ASU 2018-09 are effective upon issuance, others are effective for annual periods beginning after December 15, 2018 for public business entities, and some have been made to recently issued guidance and will be subject to the effective dates within the relevant guidance. The adoption of ASU 2018-09 is not expected to have a significant impact on our consolidated financial statements.

~~Also in July 2018, the FASB issued ASU No. 2018-10,~~ ~~Codification Improvements to Topic 842, Leases~~~~, and ASU No. 2018-11,~~ ~~Targeted Improvements to Topic 842, Leases~~~~. ASU 2018-10 updates Topic 842 in order to clarify narrow aspects of the guidance issued in ASU 2016-02,~~ ~~Leases (Topic 842)~~. ASU 2018-11 provides entities with an additional (and optional) transition method to adopt the new leases standard. Under this new transition method, an entity initially applies the new leases standard at the adoption date and recognizes a cumulative-effect adjustment to the opening balance of retained earnings in the period of adoption. Consequently, an entity’s reporting for the comparative periods presented in the financial statements in which it adopts the new leases standard will continue to be in accordance with current GAAP (Topic 840, ~~Leases~~). An entity that elects this transition method must prove the required Topic 840 disclosures for all periods that continue to be in accordance with Topic 840. The amendments in ASU 2018-10 and ASU 2018-11 are effective when ASU 2016-02 is effective, for fiscal years beginning after December 15, 2018. We do not expect the adoption of ASU 2018-10 and ASU 2018-11 to have a significant impact on our consolidated financial statements.

~~In August 2018, the FASB issued ASU No. 2018-13,~~ ~~Disclosure Framework—Changes to the Disclosure Requirements for Fair Value Measurement~~. ASU 2018-13 modifies the disclosure requirements on fair value measurements in Topic 280, Fair Value Measurement, including the consideration of costs and benefits. ASU 2018-13 removes the requirements to disclose (1) the amount of and reasons for transfers between Level 1 and Level 2 of the fair value hierarchy, (2) the policy for timing of transfers between levels, (3) the valuation processes for Level 3 fair value measurements, and (4) for nonpublic entities, the changes in unrealized gains and losses for the period included in earnings for recurring Level 3 fair value measurements held at the end of the reporting period. ASU 2018-13 also modifies certain disclosure requirements as follows: (1) in lieu of a rollforward for Level 3 fair value measurements, a nonpublic entity is required to disclose transfers into and out of Level 3 and purchase and issuances of Level 3 assets and liabilities, (2) for investments in certain entities that calculate net asset value, an entity is required to disclose the timing of liquidation of an investee’s assets and the date when restrictions from redemption might lapse only if the investee has communicated the timing to the entity or announced the timing publicly, and (3) the amendments clarify that the measurement uncertainty disclosure is to communicate information about the uncertainty in measurement as of the reporting date. Finally, ASU 2018-13 adds the requirements to disclose (1) the changes in unrealized gains and losses for the period included in other comprehensive income for recurring Level 3 fair value measurements held at the end of the reporting period, and (2) the range and weighted average of significant unobservable inputs used to develop Level 3 fair value measurements. The amendments in ASU 2018-13 are effective for fiscal years, and interim periods within those fiscal years, beginning after December 15, 2019. We do not expect the adoption of ASU 2018-13 to have any impact on our consolidated financial statements, however it may have an impact on our fair value disclosures.

4.Revenue from Contracts with Customers

~~Revenue from Contracts with Customers~~

The Company adopted ASU 2014-09, along with all subsequent related ASUs impacting revenue from contracts with customers (collectively, “the new revenue recognition standard”), effective January 1, 2018, using the modified retrospective method of adoption. The Company has applied the new revenue recognition standard for the year ended December 31, 2018 with the cumulative effect of initially applying the new accounting recognized on January 1, 2018 as an adjustment to opening accumulated deficit. This adjustment reflects only contracts that were not completed as of January 1, 2018.

We earn revenues related to our licensing and distribution agreements. The terms of these agreements may include payment to us of non-refundable up-front license fees, funding or reimbursement of research and development efforts, milestone payments if specified objectives are achieved, and/or royalties on product sales. The new revenue recognition standard generally results in the delay of revenue recognition for the Company, as compared to the previous guidance. Previously, the Company recognized revenue related to non-refundable up-front license fees either immediately upon contract execution, or over the estimated period required to fulfill the related obligations. Under the new revenue recognition standard, the Company will generally be required to defer any up-front license fees and pre-market milestones, and recognize the revenue over the period beginning with initial product sale through the end of the initial term of the agreement.

The cumulative effect of the change on accumulated deficit as of January 1, 2018 was an increase of $700,000, consisting of $100,000 related to an up-front payment received upon execution of an exclusive license and distribution agreement with Sayre Therapeutics (“Sayre”) for the development and commercialization of Tc99m tilmanocept in India in June 2017, and $600,000 related to up-front and milestone payments received pursuant to an exclusive licensing and distribution agreement with Beijing Sinotau Medical Research Co., Ltd. (“Sinotau”) for the marketing and distribution of Tc99m tilmanocept in China executed in August 2014. The following table compares deferred revenue as if the new revenue recognition standard had not been adopted to the amounts in the consolidated financial statements reflecting the adoption. Deferred revenue, the current portion of which is included in accrued liabilities and other in the consolidated balance sheets, and accumulated deficit are the only financial statement line items that were affected by the adoption of the new revenue recognition standard.

Pre-
Adoption

Post-Adoption

Change

Deferred revenue
$ 26,061 $ 726,061 $ 700,000
Accumulated deficit
(319,908,968
)
(320,608,968
)
(700,000
)

During the year ended December 31, 2018, the Company recognized revenue from contracts with customers of approximately $338,000. The Company did not recognize any related impairment losses during those periods.

Navidea is focused on the development and commercialization of precision immunodiagnostic agents and immunotherapeutics. We manage our business based on two primary types of drug products: (i) diagnostic substances, including Tc99m tilmanocept and other diagnostic applications of our Manocept platform, and (ii) therapeutic development programs, including all therapeutic applications of our Manocept platform ~~and all development programs undertaken by MT.~~ Tc99m tilmanocept, which the Company has a license to distribute outside of Canada, Mexico and the United States, is the only one of the Company’s drug product candidates that has been approved for sale in any market. The Company has license and distribution agreements in place in ~~Europe,~~ India and China, however Tc99 tilmanocept has only been approved for sale in ~~Europe.~~Europe and Australia. On May 11, 2020, the Company terminated its license and distribution agreement in Europe and Australia.

~~In April 2018, the~~The Company ~~executed~~also has an agreement in place to provide Meilleur Technologies, Inc., (“Meilleur”), a wholly-owned subsidiary of Cerveau Technologies, Inc. (“Cerveau”), worldwide rights to conduct research using NAV4694, as well as an exclusive license for the development and commercialization of NAV4694 in Australia, Canada, China, and Singapore. Meilleur also has an option to commercialize worldwide.

~~The following tables disaggregate the Company’s revenue from contracts with customers for the year ended December 31, 2018.~~

Year Ended December 31, 2018

Diagnostics

Therapeutics

Total

Royalty revenue:

Europe
$ 15,347 $ — $ 15,347
India
— — —
China
— — —
Total
$ 15,347 $ — $ 15,347

License revenue:

NAV4694 sublicense
$ 287,569 $ — $ 287,569
Tc99m tilmanocept sublicense, China
19,605 — 19,605
Total
$ 307,174 $ — $ 307,174

Other revenue:

Additional stability studies
$ 15,037 $ — $ 15,037

~~The following economic factors affect the nature, amount, timing and uncertainty of the Company’s revenue and cash flows as indicated:~~

~~Geographical Location of Customers:~~ Drug pricing models vary among different markets, which in turn may affect the royalty rates and milestones we are able to negotiate with our distributors in those markets. Royalty rates and milestone payments vary by contract but may be based in part on the potential market size in each territory. In the case of Tc99m tilmanocept, royalty rates for Europe are lower than rates in India but higher than in China.

~~Status of Regulatory Approval:~~ The majority of revenue from contracts with customers will generally be recognized after the product is approved for sale in each market. Each Tc99m tilmanocept customer operates in its own distinct regulatory environment, and the laws and pathways to drug product approval vary by market. Tc99m tilmanocept has been approved for sale in Europe, thus the Company has begun to recognize royalties from sales in Europe. Tc99m tilmanocept has not yet been approved for sale in India or China, and may never achieve approval in those markets. The regulatory pathways and timelines in those markets will impact whether and when the Company recognizes the related royalties and milestones. Similarly, NAV4694 has not yet been approved for sale in any market, thus the timing of any revenue related to that product will be dependent on the regulatory pathways and timelines in each market in which Meilleur seeks regulatory approval.

The following table summarizes the changes in contract liabilities, the current portion of which is included in accrued liabilities and other in the consolidated balance sheets, during the years ended December 31, 2018 and 2017:

Year Ended December 31,

2018

2017

Total deferred revenue, beginning of period
$ 26,061 $ 41,098
Impact of adoption of ASU 2014-09 and related standards
700,000 —
Revenue deferred related to sublicense
10,000 —
Revenue recognized from satisfaction of performance obligations
(25,037
)
(15,037
)
Total deferred revenue, end of period
$ 711,024 $ 26,061

Currently, the Company recognizes revenue from up-front license fees and pre-market milestones after the cash has been received from its customers and the performance obligations have been met. Payments for sales-based royalties and milestones are generally received after the related revenue has been recognized and invoiced. Normal payment terms generally range from 15 to 90 days following milestone achievement or royalty invoice, in accordance with each contract. ~~The Company had trade receivables of approximately $12,000 outstanding as of December 31, 2018.~~

During the year ended December 31, 2018, the Company did not recognize any revenue from performance obligations associated with long-term contracts that were satisfied (or partially satisfied) in previous periods.

Up-front and milestone payments received related to our license and distribution agreements in India and China are deferred until Tc99m tilmanocept has been approved by the regulatory authorities in each of those countries. It is not possible to determine with any degree of certainty whether or when regulatory approval for this product will be achieved in India or China, if at all. In addition, since sales of Tc99m tilmanocept have not yet begun in India or China, there is no basis for estimating whether, to what degree, or the rate at which the product will be accepted and utilized in these markets. Therefore, it is not possible to determine with any degree of certainty the expected sales in future periods in those countries. ~~Accordingly,~~As such, the Company intends to recognize revenue from up-front and milestone payments on a straight-line basis beginning at the time of regulatory approval in each country through the end of the initial term of each agreement. The initial term of each agreement is eight years in India and 10ten years in China.

F- 14

The transaction price of a contract is the amount of consideration to which the Company expects to be entitled in exchange for transferring promised goods or services to a customer. Transaction prices do not include amounts collected on behalf of third parties (e.g., sales taxes). To determine the transaction price of a contract, the Company considers the terms of the contract. For the purpose of determining transaction prices, the Company assumes that the goods or services will be transferred to the customer as promised in accordance with existing contracts and that the contracts will not be cancelled, renewed, or modified.

When estimating a contract’s transaction price, the Company considers all the information (historical, current, and forecasted) that is reasonably available to it and identifies possible consideration amounts. Most of the Company’s contracts with customers include both fixed and variable components of the transaction price. Under those contracts, some or all of the consideration for satisfied performance obligations is contingent on events over which the Company has no direct influence. For example, regulatory approval or product sales volume milestones are contingent upon the achievement of those milestones by the distributor. Additionally, the prices charged to end users of Tc99m tilmanocept, upon which royalty payments are based in ~~Europe,~~ India and China, are set by the distributor in each of those countries.

The milestone payments have a binary outcome (that is, the Company will either receive all or none of each milestone payment) and can be estimated using the most-likely-amount method. Taking into account the constraint on variable consideration, the Company has assessed the likelihood of achieving the non-sales-based milestone payments in our current contracts and has determined that it is probable the milestones will be achieved and the Company will receive the consideration. Accordingly, it is probable that including those payments in the transaction price will not result in a significant revenue reversal when the contingency is resolved. Therefore, the amount of the non-sales-based milestone payments is included in the transaction price.

Royalties are estimated based on the expected value method because they are based on a variable amount of sales representing a range of possible outcomes. However, when taking into account the constraint on variable consideration, the estimate of future royalties included in the transaction price is generally $0. This conclusion is based on the fact that Tc99m tilmanocept is early in the commercial launch process in Europe and Australia, and sales have not yet begun in India or China, therefore there is currently no basis for estimating whether, to what degree, or the rate at which the product will be accepted and utilized in these markets. Similarly, we currently have no basis for estimating whether sales-based milestones will ever be achieved. Accordingly, the Company recognizes revenue from royalties when the related sales occur and from sales-based milestones when they are achieved.

The sublicense of NAV4694 to Meilleur provides for payments to Navidea including up-front payments, milestones, an option for worldwide commercial rights, royalties on net sales, and reimbursement for product development assistance during the initial transition period. In accordance with ~~the new revenue recognition standard,~~Accounting Standards Codification No.606,Revenue from Contracts with Customers (“ASC 606”), the upfront payments were recognized upon contract inception, and reimbursement for product development assistance will be recognized on a monthly basis. Should some or all of the variable consideration from milestones, the option and royalties meet the requirements of the ~~new~~ revenue recognition standard to be included in the transaction price, those amounts will be recognized as revenue in future periods.

Up-front fees, milestones and royalties are generally non-refundable. Therefore, the Company does not estimate expected refunds nor do we adjust revenue downward. The Company will evaluate and update the estimated transaction prices of its contracts with customers at the end of each reporting period.

~~Through~~ During the years ended December 31, ~~2018,~~ 2021 and 2020, the Company recognized revenue from contracts with customers of approximately $46,000 and $119,000, respectively. During the years ended December 31, 2021 and 2020, the Company did not recognize any related impairment losses, nor did the Company recognize any revenue from performance obligations associated with long-term contracts that were satisfied (or partially satisfied) in previous periods.

F- 15

The following table disaggregates the Company’s revenue from contracts with customers for the years ended December 31, 2021 and 2020.

	Years Ended December 31,
	2021		2020
Royalty revenue:
Tc99m tilmanocept - Europe	$	0	$	7,995

License revenue:
Tc99m tilmanocept - Europe	$	45,615	$	110,730

The following economic factors affect the nature, amount, timing and uncertainty of the Company’s revenue and cash flows as indicated:

Geographical Location of Customers: Drug pricing models vary among different markets, which in turn may affect the royalty rates and milestones we are able to negotiate with our distributors in those markets. Royalty rates and milestone payments vary by contract but may be based in part on the potential market size in each territory. In the case of Tc99m tilmanocept, royalty rates for Europe were lower than rates in India but higher than in China.

Status of Regulatory Approval: The majority of revenue from contracts with customers will generally be recognized after the product is approved for sale in each market. Each Tc99m tilmanocept customer operates in its own distinct regulatory environment, and the laws and pathways to drug product approval vary by market. Tc99m tilmanocept has been approved for sale in Europe, thus the Company recognized royalties from sales in Europe. Tc99m tilmanocept has not yet been approved for sale in India or China, and may never achieve approval in those markets. The regulatory pathways and timelines in those markets will impact whether and when the Company recognizes the related royalties and milestones. Similarly, NAV4694 has not yet been approved for sale in any market, thus the timing of any revenue related to that product will be dependent on the regulatory pathways and timelines in each market in which Meilleur seeks regulatory approval.

Through December 31, 2021, the Company has not capitalized any contract-related costs as contract assets.

	Year Ended December 31,
	2021		2020
Total deferred revenue, beginning of period	$	700,000	$	700,000
Revenue deferred related to sublicense		0		160,000
Refund of deferred revenue related to sublicense		0		(160,000	)
Revenue recognized from satisfaction of performance obligations		0		0
Total deferred revenue, end of period	$	700,000	$	700,000

The Company had license revenue receivable of approximately $1,000 and $59,000 outstanding as of December 31, 2021 and 2020, respectively.

In addition to revenue from contracts from customers, we also generate revenue from ~~NIH~~National Institutes of Health (“NIH”) grants to support various product development initiatives. The ~~new~~ revenue recognition standard applies to revenue from contracts with customers. A customer is defined as a party that has contracted with an entity to obtain goods or services that are an output of the entity’s ongoing major or central operations in exchange for consideration. The Company’s ongoing major or central operations consist of the development and commercialization of precision immunodiagnostic agents and immunotherapeutics. The NIH and its various institutes are responsible for biomedical and public health research and provide major biomedical research funding to non-NIH research facilities and entities such as Navidea. While the Company will directly benefit from any knowledge gained from the project, there is also a public health benefit provided, which justifies the use of public funds in the form of the grants. Based on the nature of the Company’s operations and the terms of the grant awards, Navidea ~~and the NIH do~~ does not have a vendor-customer relationship with the NIH and the grant awards are outside the scope of the ~~new~~ revenue recognition standard. Accordingly, the ~~new~~ revenue recognition standard need not be applied ~~retrospectively~~ to the ~~contract as~~NIH grants. During the years ended December 31, 2021 and 2020, the Company recognized grant revenue of ~~January 1, 2018.~~$88,000 and $696,000, respectively.

F- 16

5.	~~Fair Val~~ue

~~The~~On May 11, 2020 (the “Termination Date”), the Company entered into a Termination Agreement (the “Termination Agreement”) with SpePharm AG (“SpePharm”) and Norgine BV (“Norgine”) which terminated that certain Exclusive License Agreement dated March 5, 2015 (as amended to date, the “License Agreement”). Under the License Agreement, SpePharm had the exclusive right to develop, manufacture and commercialize the Company’s ~~available-for-sale securities consist of certificates of deposit which are measured using Level 2 inputs.~~products approved for radiolabeling with Tc99m and containing Lymphoseek® (collectively, the “Products”) in several jurisdictions abroad, including the United Kingdom, France, Germany, Australia and New Zealand (collectively, the “Licensed Territory”). In exchange for such rights, the Company was entitled to certain royalty payments.

~~MT issued warrants~~Pursuant to ~~purchase MT Common Stock with certain characteristics including a net settlement provision~~the Termination Agreement, the parties agreed that ~~require~~neither owed the ~~warrants to be accounted for~~other any payments due under the License Agreement as ~~a derivative liability at fair value on the consolidated balance sheets. The estimated fair value~~ of the ~~MT warrants is $63,000 at both December 31, 2018~~Termination Date and ~~2017, is~~that, among other things, SpePharm no longer has any right in, nor claim to, any intellectual property owned by the Company or its affiliates anywhere in the world. SpePharm also agreed to perform certain wind-down activities (the “Wind-Down Activities”) during the six-month period following the Termination Date (the “Transition Period”), which Transition Period was extended by ninety days. The Wind-Down Activities included, without limitation, SpePharm transferring to the Company or its designee(s) the regulatory approvals controlled by SpePharm or its affiliates for the purpose of marketing, distributing and selling the Products in the Licensed Territory. SpePharm also transferred to the Company certain tenders and other ~~liabilities on~~customer and sales contracts related to the ~~accompanying consolidated balance sheets, and will continue~~Products. Subject to ~~be measured on a recurring basis. See Notes 1(m) and 10.~~

~~The following table sets forth, by level, financial assets and liabilities measured at fair value on a recurring basis:~~ the terms of the Termination Agreement, Norgine, an affiliate of SpePharm, agreed to guarantee SpePharm’s performance of its obligations under the Termination Agreement. Although the Transition Period has elapsed, SpePharm continued to fulfill customer orders until the Company obtained the regulatory license required to distribute the product in Europe, which license was received in the fourth quarter of 2021.

Assets and Liabilities Measured at Fair Value on a Recurring Basis as of December 31, 2018

Description

Quoted Prices in
Active Markets
for Identical
Liabilities
(Level 1)

Significant
Other
Observable
Inputs
(Level 2)

Significant
Unobservable
Inputs
(Level 3)

Total

Assets:

Certificates of deposit
$ — $ 799,270 $ — $ 799,270
Liabilities:

Liability related to MT warrants
$ — $ — $ 63,000 $ 63,000

Assets and Liabilities Measured at Fair Value on a Recurring Basis as of December 31, 2017

Description

Quoted Prices in
Active Markets
for Identical
Liabilities
(Level 1)

Significant
Other
Observable
Inputs
(Level 2)

Significant
Unobservable
Inputs
(Level 3)

Total

Assets:

Certificates of deposit
$ — $ 1,797,604 $ — $ 1,797,604
Liabilities:

Liability related to MT warrants
$ — $ — $ 63,000 $ 63,000

~~Valuation Processes-Level 3 Measurements:~~ ~~The Company utilizes third-party valuation services that use complex models such as Monte Carlo simulation to estimate the value of our financial liabilities.~~

~~Sensitivity Analysis-Level 3 Measurements:~~ Changes in the valuation of MT as a whole may cause material changes in the fair value of the MT warrants. Significant increases (decreases) in the valuation of MT, such as may be the result of additional financing, could result in a higher (lower) fair value measurement. A change in the valuation of MT would not necessarily result in a directionally similar change in the value of the MT warrants.

There were no Level 1 or Level 2 liabilities outstanding at any time during the years ended December 31, 2018 and 2017. There were no transfers in or out of our Level 1 or Level 2 liabilities during the years ended December 31, 2018 and 2017. Changes in the estimated fair value of our Level 3 liabilities relating to unrealized gains (losses) are recorded as changes in fair value of financial instruments in the consolidated statements of operations. The change in the estimated fair value of our Level 3 liabilities during the year ended December 31, 2017 was an approximate decrease of $153,000.

6.4.	Stock-Based Compensation

For the years ended December 31, ~~2018~~ 2021 and ~~2017,~~2020, our total stock-based compensation expense, which includes reversals of expense and incremental expense for certain modified, forfeited or cancelled awards, was approximately ~~$307,000~~$471,000 and ~~$394,000,~~$231,000, respectively. We have not recorded any income tax benefit related to stock-based compensation for the years ended December 31, ~~2018~~ 2021 and ~~2017.~~2020.

On November 23, 2021, our former Chief Executive Officer, Chief Operating Officer and Chief Financial Officer, Jed A. Latkin, signed a Separation Agreement and General Release (the “Separation Agreement”) in connection with his resignation from those positions and as a director on October 24, 2021 (the “Separation Date”). Pursuant to the Separation Agreement, among other things, the Company agreed to provide Mr. Latkin with certain separation benefits, commencing on the “Effective Date,” defined as the eighth day after Mr. Latkin signed, without revoking, the Separation Agreement. On the Effective Date, each of Mr. Latkin’s unvested stock options vested, and all of his vested stock options (covering 69,918 shares) and previously unvested options (covering 333,332 shares) may be exercised by Mr. Latkin on or before the earlier of the fifth anniversary of the Separation Date and the original expiration date. On the Effective Date, each of Mr. Latkin’s 33,333 outstanding unvested restricted stock units became fully vested, and all of such restricted stock units were settled within thirty days after the Separation Date, less applicable withholding in shares of common stock. As a result of these equity award modifications, the Company reversed prior expense of $503,000 and recognized incremental expense of $243,000 during the fourth quarter of 2021.

A summary of the status of our stock options as of December 31, ~~2018,~~ 2021, and changes during the year then ended, is presented ~~below:~~ below.

	Year Ended December 31, 2018									Year Ended December 31, 2021
	Number of Options			Weighted Average Exercise Price		Weighted Average Remaining Contractual Life (in years)		Aggregate Intrinsic Value		Number of Options			Weighted Average Exercise Price		Weighted Average Remaining Contractual Life (in years)	Aggregate Intrinsic Value
Outstanding at beginning of year		3,687,679		$	1.50
Outstanding, January 1, 2021											549,970		$	8.81
Granted		470,000			0.53						459,500			1.94
Exercised		—			—						(4,000	)		1.06
Canceled and forfeited		(992,510	)		1.86						(83,590	)		4.70
Expired		(7,000	)		0.66						(2,090	)		61.75
Outstanding at end of year		3,158,169		$	1.24		6.6	$	—
Exercisable at end of year		1,502,173		$	1.87		4.4	$	—
Outstanding, December 31, 2021											919,790		$	5.67	6.5	$	—
Exercisable, December 31, 2021											549,024		$	8.40	4.6	$	—

The weighted average grant-date fair value of options granted in ~~2018~~2021 and ~~2017~~2020 was ~~$0.20~~$1.46 and ~~$0.19,~~$1.36, respectively. During ~~2017, 50,000~~2021, 4,000 stock options with an aggregate intrinsic value of ~~$4,400~~$2,500 were exercised in exchange for issuance of ~~50,000~~4,000 shares of our ~~common stock,~~Common Stock, resulting in gross proceeds of ~~$18,100.~~ $4,240. No stock options were exercised during ~~2018. In 2018 and 2017, the~~2020. The aggregate fair value of stock options vested during ~~the year~~2021 and 2020 was $122,000 and $0, ~~in both years.~~respectively.

A summary of the status of our unvested restricted stock as of December 31, ~~2018,~~ 2021, and changes during the year then ended, is presented ~~below:~~below.

Year Ended
December 31, 2018

Number of
Shares

Weighted
Average
Grant-Date
Fair Value

Unvested at beginning of year
150,000 $ 0.51
Granted
200,000 0.37
Forfeited
(50,000
)
0.36
Vested
(200,000
)
0.47
Unvested at end of year
100,000 $ 0.37

	Year Ended December 31, 2021
	Number of Shares			Weighted Average Grant-Date Fair Value
Unvested, January 1, 2021		60,000		$	2.90
Granted		105,000			1.48
Vested		(70,000	)		2.81
Unvested, December 31, 2021		95,000		$	1.40

F- 17

During ~~2018~~2021 and ~~2017, 200,000~~2020, 70,000 and ~~207,000~~15,000 shares, respectively, of restricted stock vested with aggregate vesting date fair values of ~~$59,000~~$113,000 and ~~$99,000,~~$17,000, respectively.

In March 2018, 100,000 shares of restricted stock held by a non-employee director with an aggregate fair value of $36,000 vested upon his retirement from the Board. In August 2018, 50,000 shares of restricted stock held by a non-employee director with an aggregate fair value of $7,000 were forfeited as a result of his departure from the Board. During ~~2018, 100,000~~2021 and 2020, 20,000 and 15,000 shares of restricted stock held by non-employee directors with an aggregate fair ~~value~~values of ~~$23,000~~$43,000 and $17,000, respectively, vested as scheduled according to the terms of the restricted stock agreements.

In October 2017, 50,000 shares of restricted stock held by a non-employee director with an aggregate fair value of $22,000 were forfeited as a result of his departure from the Board. During 2017, 140,000 shares of restricted stock held by non-employee directors with an aggregate fair value of $65,000 vested as scheduled according to the terms of the restricted stock agreements. Also during 2017, 17,000 shares of restricted stock held by a non-employee director with an aggregate fair value of $9,000, and 50,000 shares of restricted stock held by an executive officer with an aggregate fair value of $25,000, were vested by Board action after determination that the vesting events would not occur due to changes in the Company’s development programs.

As of December 31, ~~2018,~~ 2021, there was approximately ~~$71,000~~$320,000 of total unrecognized compensation cost related to stock option and restricted stock awards, which we expect to recognize over remaining weighted average vesting terms of ~~1.2~~1.8 years. ~~See Note 1(e).~~

7.5.	~~(Loss)~~ ~~Earnings~~Loss Per Share

Basic ~~(loss) earnings~~loss per share is calculated by dividing net ~~(loss) income~~loss attributable to common stockholders by the weighted-average number of common ~~shares and, except for periods with a~~shares. Diluted loss ~~from operations, participating securities outstanding during the period. Diluted (loss) earnings~~ per share reflects additional common shares that would have been outstanding if dilutive potential common shares had been issued. Potential common shares that may be issued by the Company include ~~convertible debt,~~ convertible preferred stock, options and warrants.

The following table sets forth the reconciliation of the weighted average number of common shares outstanding used to compute basic and diluted earnings (loss) per share for the years ended December 31, 2018 and 2017:

2018

2017

Weighted average shares outstanding, basic
170,535,343 161,592,569
Dilutive shares related to warrants
— 4,273,889
Unvested restricted stock
— 150,000
Weighted average shares outstanding, diluted
170,535,343 166,016,458

Diluted ~~(loss) earnings~~loss per common share for the years ended December 31, ~~2018~~ 2021 and ~~2017~~2020 excludes the effects of ~~17.9 million~~1,892,114 and ~~14.5 million~~1,541,844 common share equivalents, respectively, since such inclusion would be anti-dilutive. The excluded shares consist of common shares issuable upon exercise of outstanding stock options and ~~warrants, and upon the conversion of convertible debt and convertible preferred stock.~~warrants.

The Company’s unvested stock awards contain nonforfeitable rights to dividends or dividend equivalents, whether paid or unpaid (referred to as “participating securities”). Therefore, the unvested stock awards are required to be included in the number of shares outstanding for both basic and diluted earnings per share calculations. However, due to our loss from continuing operations, ~~100,000~~95,000 and ~~150,000~~60,000 shares of unvested restricted stock for the years ended December 31, ~~2018~~ 2021 and ~~2017,~~2020, respectively, were excluded in determining basic and diluted loss per share because such inclusion would be anti-dilutive.

8.6.	~~Accounts~~Stock Subscriptions and Other Receivables and Concentrations of Credit Risk

~~Accounts~~Stock subscriptions and other receivables at as of December 31, ~~2018~~ 2021 and ~~2017~~2020 consist of the following:

2018

2017

Guaranteed earnout receivable, current
$ — $ 8,084,392
Trade
12,378 —
Other
8,773 53,480
Total accounts and other receivables
$ 21,151 $ 8,137,872

	2021		2020
Related parties	$	86,796	$	0
Stock subscriptions		0		2,925,000
License revenue		1,021		58,754
Grant revenue		919		1,117
Other		4,256		2,448
Total stock subscriptions and other receivables	$	92,992	$	2,987,319

At As of December 31, ~~2018,~~2021 and 2020, approximately ~~47%~~0% and 98%, respectively, of net ~~accounts~~stock subscriptions and other receivables were due from ~~Meilleur. At~~ investors. As of December 31, ~~2017, approximately 99% of net accounts~~ 2021 and ~~other receivables were due from Cardinal Health 414. As of December 31, 2018 and 2017,~~2020, there was no0 allowance for doubtful accounts. We do not believe we are exposed to significant credit risk related to the ~~receivable~~receivables due from ~~Meilleur~~related parties based on receipt of a majority of these amounts prior to the ~~timely payment history~~filing of ~~the entity.~~this Annual Report on Form 10-K. We believe that we have adequately addressed credit risks in estimating the allowance for doubtful accounts. ~~See Note 1(h).~~

97.

Inventory

The components of net inventory as of December 31, 2021 and 2020 are presented in the following table.

	December 31, 2021		December 31, 2020
Materials	$	50,000	$	77,750
Finished goods		101,155		92,048
Total inventory	$	151,155	$	169,798

During 2021 and 2020, we utilized $28,000 and $11,000, respectively, of materials inventory for process development purposes. Also during 2021 and 2020, we allocated $0 and $39,000, respectively, of finished goods inventory for use in clinical trials. These transactions were recorded in research and development expense in the consolidated statement of operations.

F- 18

.8.

Property and Equipment

The major classes of property and equipment are ~~as follows:~~presented in the following table.

	Useful Life (in years)			2018		2017		Useful Life (years)			2021		2020
Purchased software									3		$	320,435	$	320,435
Production machinery and equipment	3	–	5	$	575,091	$	575,091		5			214,356		214,356
Other machinery and equipment, primarily computers and research equipment	5				323,259		293,757	3	–	5		304,492		297,315
Leasehold improvements*								Term of Lease				23,511		12,448
Furniture and fixtures	7				4,327		4,327		7			3,512		825
Purchased software	3				336,060		320,435
Leasehold improvements*	Term of Lease				12,448		12,448
Total property and equipment				$	1,251,185	$	1,206,058				$	866,306	$	845,379

We amortize leasehold improvements over the term of the lease, which in all cases is shorter than the estimated useful life of the asset.

~~No property or equipment was under capital lease at December 31, 2018~~

During 2021 and ~~2017. During 2018 and 2017,~~2020, we recorded ~~$121,000~~$36,803 and ~~$232,000,~~$33,929, respectively, of depreciation and amortization related to property and equipment. ~~See Note 1(i).~~

10.9.

~~Investment in Macrophage Therapeutics, Inc.~~Accounts Payable, Accrued Liabilities and Other

~~In March 2015, MT, our previously wholly-owned subsidiary, entered into~~Accounts payable as of December 31, 2021 and 2020 includes an aggregate of $57,000 and $66,000 respectively, due to related parties for director fees. Accrued liabilities and other as of December 31, 2021 and 2020 includes an aggregate of $1.2 million and $755,000, respectively, due to related parties for accrued separation costs, bonuses and benefits. During the second quarter of 2021, the Company began paying director fees in both cash and stock. As a ~~Securities Purchase Agreement to sell up to 50 shares~~result, the cash portion of its Series A Convertible Preferred Stock (“MT Preferred Stock”) and warrants to purchase up to 1,500 shares of MT Common Stock to the MT Investors for a purchase price of $50,000 per unit. A unit consists of one share of MT Preferred Stock and 30 warrants to purchase MT Common Stock. Under the agreement, 40% of the MT Preferred Stock and warrantsdirector fees due are ~~committed to be purchased by Dr. Goldberg,~~included in accounts payable and the ~~balance by Platinum. The full 50 shares of MT Preferred Stock~~stock portion are included in accrued liabilities and warrants that may be sold under the agreement are convertible into, and exercisable for, MT Common Stock representing an aggregate 1% interest on a fully converted and exercised basis. Navidea owns the remainder of the MT Common Stock. On March 11, 2015, definitive agreements with the MT Investors were signed for the sale of the first 10 tranche of shares of MT Preferred Stock and warrants to purchase 300 shares of MT Common Stock to the MT Investors, with gross proceeds to MT of $500,000. The MT Common Stock held by parties other ~~than Navidea is reflected on~~in the consolidated balance ~~sheets~~sheet as ~~a noncontrolling interest.~~

The warrants have certain characteristics including a net settlement provision that require the warrants to be accounted for as a derivative liability at fair value, with subsequent changes in fair value included in earnings. The fair value of ~~the warrants was estimated to be $63,000 at issuance and at~~ December 31, ~~2018~~2021. During the fourth quarter of 2021, certain directors elected to defer receipt of both cash and ~~2017. See Notes 1(m) and 5. In addition, certain provisions of the Securities Purchase Agreement obligate the MT Investors to acquire the remaining MT Preferred Stock and related warrants~~stock for $2.0 million at the option of MT. The estimated relative fair value of this put option was $113,000 at issuance based on the Black-Scholes option pricing model and is classified within stockholders' equity.

In addition, we entered into a Securities Exchange Agreement with the MT Investors providing them an option to exchange their MT Preferred Stock for our common stock in the event that MT has not completed a public offering with gross proceeds to MT ofdirector fees until at least $50 million by the second anniversary of the closing of the initial sale of MT Preferred Stock, at an exchange rate per share obtained by dividing $50,000 by the greater of (i) 80% of the twenty-day volume weighted average price per share of our common stock on the second anniversary of the initial closing or (ii) $3.00. To the extent that the MT Investors do not timely exercise their exchange right, MT has the right to redeem their MT Preferred Stock for a price equal to $58,320 per share. We also granted MT an exclusive sublicense for certain therapeutic applications of the Manocept technology.

In December 2015 and May 2016, Platinum contributed a total of $200,000 to MT. MT was not obligated to provide anything in return, although it was considered likely that the MT Board would ultimately authorize some form of compensation to Platinum. The Company initially recorded the entire $200,000 as a current liability pending determination of the form of compensation.

In July 2016, MT’s Board of Directors authorized modification of the original investments of $300,000 by Platinum and $200,000 by Dr. Goldberg to a convertible preferred stock with a 10% PIK coupon retroactive to the time the initial investments were made. The conversion price of the preferred will remain at the $500 million initial market cap but a full ratchet was added to enable the adjustment of conversion price, warrant number and exercise price based on the valuation of the first institutional investment round. In addition, the MT Board authorized issuance of additional convertible preferred stock with the same terms to Platinum as compensation for the additional $200,000 of investments made in December 2015 and May 2016. Based on the MT Board’s authorization of additional equity, the Company reclassified the additional $200,000 from a current liability to equity during the year ended December 31, 2017. As of the date of filing of this Form 10-K, final documents related to the above transactions authorized by the MT Board have not been completed.

In August 2018, the Company entered into the Agreement with Dr. Michael Goldberg related to his resignation from his positions as an executive officer and a director of Navidea. Among other things, the Agreement provided that Dr. Goldberg would become Chief Executive Officer of MT, and that MT would redeem all of Dr. Goldberg’s MT preferred stock and issue to Dr. Goldberg MT super voting common stock equal to 5% of the outstanding shares of MT, subject to execution of Definitive Agreements. As of the date of filing of this Annual Report on Form 10-K, the Definitive Agreements have not yet been signed.

On February 11, 2019, Dr. Goldberg represented to the MT Board that he had, without MT Board or shareholder approval, created a subsidiary of MT, transferred all of the assets of MT into the subsidiary, and then issued himself stock in the subsidiary. On February 19, 2019, Navidea notified MT that it was terminating the sublicense effective March 1, 2019 because MT became insolvent in violation of the sublicense agreement. On February 20, 2019, the Board of Directors of MT removed Dr. Goldberg as President and Chief Executive Officer of MT and from any other office of MT to which he may have been appointed or in which he was serving. Dr. Goldberg remains a member of the MT Board, together with Michael Rice and Dr. Claudine Bruck. Mr. Rice and Dr. Bruck remain members of the board of directors of Navidea. The MT Board then appointed Mr. Latkin to serve as President and Chief Executive Officer of MT.

On March 7, 2019, Dr. Goldberg filed a complaint against Navidea and MT in the United States District Court for the Southern District of New York. The Complaint alleges a breach of contract claim against both Navidea and MT for failure to pay to Dr. Goldberg funds allegedly due to him under the Platinum Note. The Complaint further alleges a breach of contract claim against Navidea due to Navidea’s failure to issue 23.5 million shares to Dr. Goldberg, to issue MT Super Voting Common Stock, by removing Dr. Greene from the MT Board of Directors, by appointing Mr. Rice and Dr. Bruck to the MT Board of Directors, and by terminating Dr. Goldberg as CEO of MT. See Note 15.

11.	~~Accounts Payable,~~ ~~Accrued~~ ~~Liabilities and Other~~

At December 31, 2017, approximately $96,000 of accounts payable was being disputed by the Company related to unauthorized expenditures by a former executive, which were incurred during the year ended December 31, 2016.2022.

Accrued liabilities and other at as of December 31, ~~2018~~ 2021 and ~~2017, including an aggregate of $1.6 million and $975,000 due to related parties for accrued termination costs, bonuses and director fees, consist of~~2020 are presented in the ~~following:~~following table.

	2018		2017		2021		2020
Contracted services					$	1,913,756	$	1,725,866
Compensation	$	1,637,337	$	915,672		1,194,719		755,494
Contracted services		866,934		923,115
Other		12,776		19,061		40,865		31,634
Total accrued liabilities and other	$	2,517,047	$	1,857,848	$	3,149,340	$	2,512,994

12.10.

Notes Payable

~~Platinum~~First Insurance Funding

In November 2019, we prepaid $349,000 of insurance premiums through the issuance of a note payable to First Insurance Funding (“FIF”) with an interest rate of 5.0%. The note was payable in eight monthly installments of $44,000, with the final payment made in July 2012, we entered into an agreement with Platinum to provide us with a credit facility of up to $50.0 million. Following the approval of Tc99m tilmanocept, Platinum was committed under the terms of the agreement to extend up to $35.0 million in debt financing2020.

Interest expense related to the ~~Company. The agreement also provided for Platinum to extend an additional $15.0 million on terms to be negotiated. Through June 25, 2013, we drew a total of $8.0 million under~~FIF note payable totaled $5,000 during the ~~original facility.~~year ended December 31, 2020.

IPFS Corporation

In ~~June 2013, in connection with entering into~~November 2020, we prepaid $442,000 of insurance premiums through the issuance of a ~~Loan Agreement with General Electric Capital~~note payable to IPFS Corporation (“~~GECC��~~IPFS”) ~~and MidCap Financial SBIC, LP (“MidCap”) (the “GECC/MidCap Loan Agreement”), the Company and Platinum entered into~~with an ~~Amendment to the Platinum Loan Agreement (the “First Platinum Amendment”)~~interest rate of 3.5%. ~~Concurrent~~The note was payable in seven monthly installments of $64,000, with the ~~execution~~final payment made in June 2021. In November 2021, we prepaid $566,000 of insurance premiums through the ~~First Platinum Amendment, the Company delivered~~issuance of a note payable to IPFS with an Amended and Restated Promissory Note (the “First Amended Platinum Note”) to Platinum, which amended and restated the original promissory note issued to Platinum, in the principal amount of up to $35.0 million. The First Amended Platinum Note also adjusted the interest rate toof 4.36%. The note is payable in five monthly installments of $114,000, with the ~~greater of (a) the U.S. Prime Rate as reported~~final payment due in ~~the Wall Street Journal plus 6.75%; (b) 10.0%; or (c) the highest rate of interest then payable pursuant to the GECC/MidCap Loan Agreement plus 0.125%.~~April 2022.

~~In connection with~~Interest expense related to the ~~First Platinum Amendment,~~IPFS notes payable totaled $6,000 and $1,000 during the ~~Company~~ years ended December 31, 2021 and ~~Platinum entered into a Warrant Exercise Agreement (“Exercise Agreement”), pursuant to which Platinum exercised its Series X Warrant and Series AA Warrant.~~2020, respectively. The ~~warrants were exercised on a cashless basis by canceling a portion~~balance of the ~~indebtedness outstanding under the Platinum Loan Agreement equal to $4.8 million, the aggregate exercise price~~IPFS notes was approximately $453,000 and $379,000 as of ~~the warrants. Pursuant to the Exercise Agreement,~~December 31, 2021 and 2020, respectively, and was included in lieu of common stock, Platinum received on exercise of the warrants 2,364.9 shares of the Company’s Series B Convertible Preferred Stock (the “Series B Preferred Stock”), convertible into 7,733,223 shares of our common stocknotes payable, current in the ~~aggregate (3,270 shares of common stock per preferred share).~~

In March 2014, in connection with entering into a Loan and Security Agreement (the “Oxford Loan Agreement”) with Oxford Finance, LLC, we entered into a second amendment to the Platinum Loan Agreement (the “Second Platinum Amendment”). Concurrent with the execution of the Second Platinum Amendment, the Company delivered an Amended and Restated Promissory Note (the “Second Amended Platinum Note”) to Platinum, which amended and restated the First Amended Platinum Note. The Second Amended Platinum Note adjusted the interest rate to the greater of (i) the U.S. prime rate as reported in The Wall Street Journal plus 6.75%, (ii) 10.0%, and (iii) the highest rate of interest then payable by the Company pursuant to the Oxford Loan Agreement plus 0.125%.

In May 2015, in connection with the execution of the CRG Loan Agreement (discussed below), the Company amended the existing Platinum credit facility to allow this facility to remain in place in a subordinated role to the CRG Loan (the “Third Platinum Amendment”). Among other things, the Third Platinum Amendment (i) extended the term of the Platinum Loan Agreement until a date six months following the maturity date or earlier repayment of the CRG Term Loan; (ii) changed the interest rate to the greater of (a) the U.S. prime rate as reported in The Wall Street Journal plus 6.75%, (b) 10.0% and (c) the highest rate of interest then payable pursuant to the CRG Term Loan plus 0.125%; (iii) required such interest to compound monthly; and (iv) changed the provisions of the Platinum Loan Agreement governing Platinum’s right to convert advances into common stock of the Company. The Third Platinum Amendment provided for the conversion of all principal and interest outstanding under the Platinum Loan Agreement, but not until such time as the average daily volume weighted average price of the Company’s common stock for the ten preceding trading days exceeds $2.53 per share. The Third Platinum Amendment became effective upon initial funding of the CRG Loan Agreement.consolidated balance sheets.

F- 19

Paycheck Protection Program

The CARES Act was enacted on March 27, 2020. Among the provisions contained in the CARES Act was the creation of the PPP that provides for SBA Section 7(a) loans for qualified small businesses. PPP Loan proceeds are available to be used to pay for payroll costs, including salaries, commissions, and similar compensation, group health care benefits, and paid leaves; rent; utilities; and interest on certain other outstanding debt. On May 18, 2020, the Lender funded the PPP Loan in the amount of $366,000. In accordance with the ~~terms~~loan forgiveness requirements of the CARES Act, the Company used the proceeds from the PPP Loan primarily for payroll costs, rent and utilities. On February 23, 2021, the Lender notified the Company that the entire PPP Loan amount of $366,000 had been forgiven. The forgiveness was recorded as a ~~Section 16(b) Settlement Agreement, Platinum agreed to forgive interest owed~~gain on extinguishment of debt on the ~~credit facility in an amount equal to 6%, effective July 1, 2016.~~ consolidated statement of operations. See Note 2.

Summary

During the years ended December 31, ~~2018~~ 2021 and ~~2017, $153,000 and $265,000, respectively,~~2020, we recorded interest expense of ~~interest was compounded and added~~$6,000 in both periods related to ~~the balance~~our notes payable. Annual principal maturities of ~~the Platinum Note.~~our notes payable are $453,000 in 2022.

11.

Leases

We currently lease approximately 5,000 square feet of office space at 4995 Bradenton Avenue, Dublin, Ohio, as our principal offices, at a monthly base rent of approximately $3,000. The current lease term expires in June 2023.

In ~~connection~~ addition, we currently lease approximately 25,000 square feet of office space at 5600 Blazer Parkway, Dublin, Ohio, formerly our principal offices, at a monthly base rent of approximately $27,000 during 2021. The current lease term expires in October 2022 with an option to extend for an additional five years. The Company does not intend to renew this lease. In June 2017, the ~~closing~~Company executed a sublease arrangement for the Blazer space, providing for monthly sublease payments to Navidea of approximately $39,000 through October 2022.

We currently lease office equipment at a monthly payment of approximately $100, expiring in October 2024. We also leased a vehicle at a monthly payment of approximately $300, which expired in September 2021.

Total operating lease expense was $172,000 and $198,000 for the years ended December 31, 2021 and 2020, respectively. Operating lease expense was recorded in selling, general and administrative expenses on our consolidated statements of operations.

F- 20

The following table presents information about the amount, timing and uncertainty of cash flows arising from the Company’s operating leases as of December 31, 2021.

Maturity of Lease Liabilities	Operating Lease Payments
2022	$	291,111
2023		19,699
2024		1,355
Total undiscounted operating lease payments		312,165
Less imputed interest		16,159
Present value of operating lease liabilities	$	296,006

Balance Sheet Classification
Current lease liabilities	$	275,718
Noncurrent lease liabilities		20,288
Total operating lease liabilities	$	296,006

Other Information
Weighted-average remaining lease term for operating leases (years)	0.9
Weighted-average discount rate for operating leases		10.96	%

Cash paid for amounts included in the present value of operating lease liabilities was $344,000 and $339,000 during the years ended December 31, 2021 and 2020, respectively, and is included in operating cash flows.

12.

Commitments and Contingencies

We are subject to legal proceedings and claims that arise in the ordinary course of business. In accordance with ASC Topic 450,Contingencies, we make a provision for a liability when it is both probable that a liability has been incurred and the amount of the ~~Asset Sale~~loss can be reasonably estimated. The amount of ultimate liability, if any, with respect to Cardinal Health 414 in March 2017, the Company repaid to PPCO an aggregate of approximately $7.7 million in partial satisfaction of the Company’s liabilities, obligations and indebtedness under the Platinum Loan Agreement between the Company and Platinum-Montaur, which were transferred by Platinum-Montaur to PPCO. See Note 15.these actions is unknown.

CRG Litigation

The Platinum Note is reflected on the consolidated balance sheets at its principal balance plus the estimated fair value of the embedded conversion option of $0 at December 31, 2018 and 2017. During the years ended December 31, 2018 and 2017, changesCompany has been engaged in the estimated fair value of the Platinum conversion option were $0 and a decrease of $153,000, respectively, and were recorded as non-cash changes in the fair value of financial instruments. The balance of the Platinum Note, including the fair value of the embedded conversion option, was $0 and $2.0 million as of December 31, 2018 and 2017, respectively.

~~Capital Royalty Partners II, L.P.~~

~~In May 2015, Navidea and MT, as guarantor, executed a Term Loan Agreement (the “CRG Loan Agreement”)~~ongoing litigation with CRG, in its capacity as a lender and as control agent for other affiliated lenders party to the CRG Loan Agreement (collectively, the ~~“Lenders”) in which the Lenders agreed to make a term loan to the Company in the aggregate principal amount of $50.0 million (the~~ “CRG ~~Term Loan”~~Lenders”), with an additional $10.0 million in loans to be made available upon the satisfaction of certain conditions stated in the CRG Loan Agreement. Closing and funding of the CRG Term Loan occurred on May 15, 2015 (the “Effective Date”). The principal balance of the CRG Term Loan bore interest from the Effective Date at a per annum rate of interest equal to 14.0%. Through March 31, 2019, the Company had the option of paying (i) 10.00% of the per annum interest in cash and (ii) 4.00% of the per annum interest as compounded interest which is added to the aggregate principal amount of the CRG Term Loan. During 2015 and 2016, a total of $1.8 million of interest was compounded and added to the balance of the CRG Term Loan. In addition, the Company began paying the cash portion of the interest in arrears on June 30, 2015. Principal was due in eight equal quarterly installments during the final two years of the term. All unpaid principal, and accrued and unpaid interest, was due and payable in full on March 31, 2021. Pursuant to a notice of default letter sent to Navidea by CRG in April 2016, the Company stopped compounding interest in the second quarter of 2016 and began recording accrued interest.

The CRG Term Loan was collateralized by a security interest in substantially all of the Company's assets. In addition, the CRG Loan Agreement required that the Company adhere to certain affirmative and negative covenants, including financial reporting requirements and a prohibition against the incurrence of indebtedness, or creation of additional liens, other than as specifically permitted by the terms of the CRG Loan Agreement. The Lenders could accelerate the payment terms of the CRG Loan Agreement upon the occurrence of certain events of default set forth therein, which include the failure of the Company to make timely payments of amounts due under the CRG Loan Agreement, the failure of the Company to adhere to the covenants set forth in the CRG Loan Agreement, and the insolvency of the Company. The covenants of the CRG Loan Agreement included a covenant that the Company shall have EBITDA of no less than $5.0 million in each calendar year during the term or revenues from sales of Tc99m tilmanocept in each calendar year during the term of at least $22.5 million in 2016, with the target minimum revenue increasing in each year thereafter until reaching $45.0 million in 2020. However, if the Company were to fail to meet the applicable minimum EBITDA or revenue target in any calendar year, the CRG Loan Agreement provided the Company a cure right if it raised 2.5 times the EBITDA or revenue shortfall in equity or subordinated debt and deposited such funds in a separate blocked account. Additionally, the Company was required to maintain liquidity, defined as the balance of unencumbered cash and permitted cash equivalent investments, of at least $5.0 million during the term of the CRG Term Loan. The events of default under the CRG Loan Agreement also included a failure of Platinum to perform its funding obligations under the Platinum Loan Agreement at any time as to which the Company had negative EBITDA for the most recent fiscal quarter, as a result either of Platinum’s repudiation of its obligations under the Platinum Loan Agreement, or the occurrence of an insolvency event with respect to Platinum. An event of default would entitle CRG to accelerate the maturity of our indebtedness, increase the interest rate from 14% to the default rate of 18% per annum, and invoke other remedies available to it under the loan agreement and the related security agreement.

~~During the course of 2016, CRG alleged multiple claims of default on the CRG Loan Agreement, and filed suit~~ in the District Court of Harris County, Texas (the “Texas Court”) ~~on April 7, 2016. On June 22, 2016, CRG exercised control over one~~relating to CRG’s claims of the Company’s primary bank accounts and took possession of $4.1 million that was on deposit, applying $3.9 million of the cash to various fees, including collection fees, a prepayment premium and an end-of-term fee. The remaining $189,000 was applied to the principal balance of the debt. Multiple motions, actions and hearings followed over the remainder of 2016 and into 2017.

On March 3, 2017, the Company entered into a Global Settlement Agreement with MT, CRG, and Cardinal Health 414. In accordance with the Global Settlement Agreement, on March 3, 2017, the Company repaid $59.0 million of its indebtedness and other obligations outstandingdefault under the terms the CRG ~~Term Loan.~~

Loan Agreement. Following a trial in December 2017, the Texas Court ruled that the Company’s total obligation to CRG was in excess of $66.0 million, limited to $66.0 million under the Global Settlement ~~Agreement.~~ Agreement (“GSA”) dated March 3, 2017. The Texas Court acknowledged only the $59.0 million payment made in March 2017, concluding that the Company owed CRG another $7.0 million, however the Texas Court did not expressly take the Company’s June 2016 payment of $4.1 million into account and awarded, as part of the ~~$66.0~~$66.0 million, amounts that had already been paid as part of the ~~$4.1~~$4.1 million. In April 2018, CRG drew approximately $7.1 million on a letter of credit that was established pursuant to the Global Settlement Agreement. This was in addition to the $4.1 million and the $59.0 million that Navidea had previously paid to CRG. The Company believes that ~~the $4.1~~this $4.1 million should be credited against the ~~$7.0~~$7.0 million and ~~is currently pursuing recovery~~has appealed the Texas Court’s judgment. The Court of ~~$4.1 million and other damages. See Note 15.~~

I~~PFS Corporation~~

~~In November 2017, we prepaid $396,000 of insurance premiums through~~Appeals dismissed the ~~issuance of a note payable to IPFS Corporation (“IPFS”) with an interest rate of 4.0%. The note was payable in ten monthly installments of $40,000, with~~Company’s appeal without reaching the final payment made in August 2018. In November 2018, we prepaid $393,000 of insurance premiums through the issuance of a note payable to IPFS with an interest rate of 5.1%. The note is payable in ten monthly installments of $40,000, with the final paymentmerits due ~~in August 2019.~~

Interest expense related to the IPFS notes payable totaled $8,000 and $12,000 during the years ended December 31, 2018 and 2017, respectively. The balance of the IPFS note was approximately $316,000 and $318,000 as of December 31, 2018 and 2017, respectively, and was included in notes payable, current in the consolidated balance sheets.

~~Summary~~

During the years ended December 31, 2018 and 2017, we recorded interest expense of $161,000 and $159,000, respectively, related to our notes payable. Of those amounts, $153,000 and $134,000 was compounded and added to the balance of our notes payable during the years ended December 31, 2018 and 2017.

~~Interest expense in the amount of $1,706,491 during the year ended December 31, 2017 has been reclassified to discontinued operations. See Note 3.~~

~~Annual principal maturities of our notes payable are $316,000 in 2019.~~

13.	~~Terminated Lease Liability~~

~~Effective June 1, 2017, Navidea relocated its Dublin, Ohio headquarters from 5600 Blazer Parkway (“Blazer”)~~ to a smaller space at 4995 Bradenton Avenue. The Company concurrently executed a sublease arrangement (“Sublease”) for the Blazer space because there is no early termination provision in the Blazer lease. The Blazer lease and the Sublease end simultaneously in October 2022.

~~In accordance with current accounting guidance, the Company initially recorded a total liability~~contractual waiver of $1.0 million, which was equal to the fair value of the remaining payments due under the Blazer Lease, net of the fair value of the payments to be received by the Company under the Sublease, and including a finder’s fee. The Company also recorded a loss on contract termination of $399,000 and a loss on disposal of assets, primarily leasehold improvements and furniture and fixtures, related to the Blazer space of $706,000. Both losses were included in selling, general and administrative expenses for the year ended December 31, 2017.

~~A summary of the changes in our terminated lease liability during the year ended December 31, 2018 is presented below:~~

Terminated
Lease
Liability

Total liability, January 1, 2018
$ 695,307
Changes in estimated future payments
(43,393
)
Payments under Blazer lease
(491,031
)
Receipts from subtenant
391,242
Accretion of liability
37,048
Total liability, December 31, 2018
$ 589,173

14.	~~Leases~~

We currently lease approximately 5,000 square feet of office space at 4995 Bradenton Avenue, Dublin, Ohio, as our principal offices. The current least term expires in June 2020, at a monthly base rent of approximately $3,000. We also lease approximately 2,000 square feet of office space at 560 Sylvan Avenue, Englewood Cliffs, New Jersey. The current lease term expires in March 2019, at a monthly base rent of approximately $3,000.

In addition, we currently lease approximately 25,000 square feet of office space at 5600 Blazer Parkway, Dublin, Ohio, formerly our principal offices. The current lease term expires in October 2022, at a monthly base rent of approximately $26,000 during 2019. In June 2017, the Company executed a sublease arrangement for the Blazer space, providing for monthly sublease payments to Navidea of approximately $39,000 through October 2022.

~~We also currently lease a vehicle. The lease term expires in September 2021, at a monthly payment of approximately $300.~~

~~As of December 31, 2018, the future minimum lease payments for the years ending December 31 are as follows:~~

Operating
Leases

2019
$ 339,202
2020
319,034
2021
306,781
2022
253,339
Total future minimum lease payments
$ 1,218,356

~~Total rental expense was $68,000 and $139,000 for the years ended December 31, 2018 and 2017, respectively. See Note 1(l).~~

15.	~~Commitments and Contingencies~~

~~We are subject to legal proceedings and claims that arise in the ordinary course of business.~~

~~Sinotau Litigation – NAV4694~~appeal.

On August 31, 2015, Sinotau filed a suit for damages, specific performance, and injunctive relief against the Company in the U.S. District Court for the District of Massachusetts alleging breach of a letter of intent for licensing to Sinotau of the Company’s NAV4694 product candidate and technology. In September 2016, the Court denied the Company’s motion to dismiss. The Company filed its answer to the complaint and the parties have filed multiple joint motions to stay the case pending settlement discussion, which to date have been granted.

In October 2017, the Company executed a letter of intent with Sinotau and Cerveau outlining a plan to sublicense to Cerveau the worldwide rights to conduct research using NAV4694, as well as grant to Cerveau an exclusive license for the development, marketing and commercialization of NAV4694 in Australia, Canada, China and Singapore. The letter of intent included a provision stating that Sinotau will release all claims in the Sinotau Litigation upon the parties’ execution of a definitive agreement; the commercial rights agreement contemplated by the letter of intent would also include a release of such claims and a covenant not to sue on such claims.

In April 2018, the Company executed an agreement to provide Meilleur worldwide rights to conduct research using NAV4694, as well as an exclusive license for the development and commercialization of NAV4694 in Australia, Canada, China, and Singapore. Meilleur also has an option to commercialize worldwide. As a result of the agreement, the litigation initiated by Sinotau was dismissed in September 2018.

~~CRG Litigation~~

Prior to the Asset Sale to Cardinal Health 414 in March 2017, all of our material assets were pledged as collateral for our borrowings under the CRG Loan Agreement. In addition to the security interest in our assets, the CRG Loan Agreement included covenants that imposed significant requirements on us. An event of default would have entitled CRG to accelerate the maturity of our indebtedness, increase the interest rate from 14% to the default rate of 18% per annum, and invoke other remedies available to it under the loan agreement and the related security agreement. During the course of 2016, CRG alleged multiple claims of default on the CRG Loan Agreement, and filed suit in the District Court of Harris County, Texas. On June 22, 2016, CRG exercised control over one of the Company’s primary bank accounts and took possession of $4.1 million that was on deposit. Multiple motions, actions and hearings followed over the remainder of 2016 and into 2017.

On March 3, 2017, the Company entered into a Global Settlement Agreement with MT, CRG, and Cardinal Health 414 to effectuate the terms of the settlement previously entered into by the parties on February 22, 2017. In accordance with the Global Settlement Agreement, on March 3, 2017, the Company repaid the $59.0 million Deposit Amount of its indebtedness and other obligations outstanding under the CRG Term Loan. Concurrently with payment of the Deposit Amount, CRG released all liens and security interests granted under the CRG Loan Documents and the CRG Loan Documents were terminated and are of no further force or effect; provided, however, that, notwithstanding the foregoing, the Company and CRG agreed to continue with their proceeding pending in the Texas Court to fully and finally determine the Final Payoff Amount. The Company and CRG further agreed that the Final Payoff Amount would be no less than $47.0 million and no more than $66.0 million. In addition, concurrently with the payment of the Deposit Amount and closing of the Asset Sale, (i) Cardinal Health 414 agreed to post a $7.0 million letter of credit in favor of CRG (at the Company’s cost and expense to be deducted from the closing proceeds due to the Company, and subject to Cardinal Health 414’s indemnification rights under the Purchase Agreement) as security for the amount by which the High Payoff Amount exceeds the Deposit Amount in the event the Company is unable to pay all or a portion of such amount, and (ii) CRG agreed to post a $12.0 million letter of credit in favor of the Company as security for the amount by which the Deposit Amount exceeds the Low Payoff Amount. In accordance with the Global Settlement Agreement, on March 3, 2017, the Company repaid $59.0 million of its indebtedness and other obligations outstanding under the CRG Term Loan. Also on March 3, 2017, Cardinal Health 414 posted a $7.0 million letter of credit, and on March 7, 2017, CRG posted a $12.0 million letter of credit, each as required by the Global Settlement Agreement.

Following a trial in December 2017, the Texas Court ruled that the Company’s total obligation to CRG was in excess of $66.0 million, limited to $66.0 million under the Global Settlement Agreement. The Texas Court acknowledged only the $59.0 million payment made in March 2017, concluding that the Company owed CRG another $7.0 million, however the Texas Court did not expressly take the Company’s June 2016 payment of $4.1 million into account and awarded, as part of the $66.0 million, amounts that had already been paid as part of the $4.1 million. The Company believes that this $4.1 million should be credited against the $7.0 million; CRG disagrees.

On January 16, 2018, the Company filed an emergency motion to set supersedeas bond and to modify judgment, describing the double recovery created by the $66.0 million award without taking into account the $4.1 million payment in June 2016, requesting that the judgment be modified to set the supersedeas amount at $2.9 million so that the Company could stay enforcement of the judgment pending appeal. The Texas Court refused to rule on this motion, and the court of appeals entered an order compelling the Texas Court to set a supersedeas amount. On March 26, 2018, the Texas Court ordered the Company to put up a supersedeas bond in the amount of $7.7 million. The Company filed for an emergency stay of the order in the appellate court in Harris County. On April 2, 2018, the appellate court denied the Company’s emergency stay motion. The Company continues to believe that the $4.1 million paid to CRG in June 2016 should be credited as payment toward the $66.0 million total, and intends to further contest the matter through the appellate court in Texas. The Company’s appeal on the merits is now fully briefed, and the Company expects a ruling on the merits appeal at some point in 2019. CRG has repeatedly filed motions seeking to have the Texas Court grant an anti-suit injunction which would purportedly restrict Navidea’s ability to proceed with litigation in Ohio. All of these motions have been denied either by the Texas Court or by the appellate court in Texas. The last such motion was denied on November 21, 2018. The case is fully briefed and awaiting a ruling. The Company expects a ruling sometime in 2019.

On April 9, 2018, CRG drew approximately $7.1 million on the Cardinal Health 414, LLC (“Cardinal Health 414”) letter of credit. These were funds to which Navidea would otherwise have been entitled. This was in addition to the ~~$4.1~~$4.1 million and the ~~$59.0~~$59.0 million that Navidea had previously paid to CRG.

~~On April 12, 2018 Navidea filed suit~~The Company has also been engaged in ongoing litigation with CRG in the Court of Common Pleas of Franklin County, Ohio ~~Court against the Lenders. The suit asserts~~(the “Ohio Court”) related to Navidea’s claims that the CRG Lenders fraudulently induced Navidea to enter into a settlement agreement and breached the terms of the same through certain actions taken by the CRG Lenders in connection with the ~~Global Settlement Agreement reached in 2017,~~GSA, pursuant to which Navidea agreed to pay up to ~~$66.0~~$66.0 million to the CRG Lenders, as well as through actions and misrepresentations by CRG after the ~~Global Settlement Agreement~~GSA was executed. The claims in that suit ~~also asserts claims~~were for breach of contract, conversion and unjust enrichment against the CRG Lenders for their collection of more than ~~$66.0~~$66.0 million, the maximum permitted under the ~~Global Settlement Agreement,~~GSA, and their double recovery of amounts paid as part of the ~~$4.1~~$4.1 million paid in June 2016 and recovered again as part of the ~~$66.0~~$66.0 million. CRG’s double recovery and recovery of more than ~~$66.0~~$66.0 million are due to CRG drawing the entire ~~$7.1~~$7.1 million on the Cardinal Health 414 letter of credit. ~~On May 22, 2018 Navidea filed an amended complaint asserting additional claims, including claims for breach~~The CRG Lenders sought a Writ of ~~confidentiality by CRG, and on June 26, 2018 CRG filed a motion seeking to dismiss the amended complaint. On August 16, 2018, the Ohio Court entered an Order granting~~Prohibition in part and overruling in part CRG’s Motion to Dismiss. While several of the Company’s claims were dismissed, the core of the Complaint, relating to the claimed $4.1million overpayment to CRG was permitted to proceed. On August 27, 2018, CRG filed a Petition with the Ohio Supreme Court ~~seeking a Writ of Prohibition against the Trial Court~~to prevent this case from moving forward, which was denied, and asserting that the Ohio Court’s denial in part of CRG’s Motion to Dismiss was improper. The Trial Court filed a motion to dismiss the writ of prohibition and the Company, after intervening in the writ of prohibition action, moved for judgment on the pleadings. Following that, proceedings ~~have~~ resumed in front of the ~~Trial~~Ohio Court. ~~Discovery is ongoing in~~Following an unsuccessful mediation on May 7, 2019, Navidea moved for summary judgment on June 28, 2019. On November 27, 2019, the Ohio Court found that when CRG collected more than $66.0 million, they took an excess recovery and breached the GSA. The Ohio Court awarded approximately $4.3 million to Navidea, plus statutory interest from April 9, 2018, the date CRG drew on the Cardinal Health 414 letter of credit. The Ohio Court also found that there was no unjust enrichment or conversion by CRG since this was a matter of contract and only contract damages were appropriate. The decision was a final appealable order and terminated the case ~~and it is anticipated that the Company will file a Motion for Summary Judgment sometime in 2019.~~

~~In a related proceeding~~ before the Ohio Court. On December 5, 2019, CRG filed a notice of appeal with Ohio’s 10th District Court ~~initially filed~~of Appeals regarding the judgment in ~~2016,~~ favor of Navidea. The briefing of the appeal concluded on March 27, 2020, and ~~under~~oral argument on the appeal was held on September 23, 2020. On March 16, 2021, Ohio’s 10th District Court of Appeals issued a decision which ~~the Global Settlement Agreement was reached in 2017,~~reversed the Ohio ~~Court has issued preliminary findings~~Court’s November 27, 2019 ruling that CRG breached the ~~settlement gave rise~~GSA and its award of $4.3 million plus statutory interest to a $66.0 million cap on amounts owed to Lenders by Navidea and that Navidea might not have been properly credited for certain funds in excess of $4.1 million previously swept by Lenders from a bank account owned by Navidea. The Ohio Court ~~also made a preliminary ruling~~of Appeals held that ~~it possessed jurisdiction to interpret the settlement agreement at issue. The Company is pursuing recovery of the $4.1 million, and other damages, in~~ the Ohio Court did not have jurisdiction to adjudicate Navidea’s claims and therefore did not rule on the factual merits of Navidea’s claims regarding CRG’s recovery in excess of the contractually agreed maximum amount. The Ohio Supreme Court declined to hear the case so the Ohio litigation has concluded.

F- 21

In April 2018, CRG asserted claims against Navidea and MT for alleged breaches of the GSA and the CRG Loan Agreement entered into by Navidea arising from the Navidea’s challenge to CRG’s drawing down on letters of credit in the ~~case filed April 12, 2018~~full amount of $7.1 million which Navidea claims resulted in an overpayment of approximately $4.2 million under the CRG Loan Agreement. CRG also seeks declaratory judgment relief that essentially mirrors their claims for affirmative relief, i.e., that the Company breached the GSA and ~~referenced above.~~indemnification provision of the CRG Loan Agreement, and that CRG did not breach the GSA.

On ~~April 11, 2018, CRG filed a new suit against the Company in~~ November 21, 2021, the Texas ~~Court. This new suit seeks a declaratory~~Court entered an interlocutory judgment declaring that CRG did not breach the ~~Global Settlement Agreement by drawing approximately $7.1 million on~~GSA, but that Navidea did breach the ~~Cardinal Health 414 letter~~GSA and the indemnification provision of ~~credit. On April 16, 2018,~~the CRG ~~moved~~Loan Agreement. In the interlocutory order, the Texas Court to issue an anti-suit injunction barring the Company from litigating in the Ohio Court. The Texas Court denied that motion on April 27, 2018. The Company moved to dismiss these claims pursuant to the Texas Citizens Participation Act. On August 17, 2018, the Texas Court denied the Company’s Motion to Dismiss. That same day, the Company took an immediate appeal of its claims under the Texas Citizens Participation Act to the Fourteenth Court of Appeals of Texas. The appeal of the denial of the Company’s motion to dismiss CRG’s complaint under the Texas Citizens Participation Act is now fully briefed and awaiting a ruling. The Company expects a ruling sometime in 2019.

On July 11, 2018, CRG filed a first amended petition in the new suit. This amended petition includes the prior request for declaratory judgment that CRG did not breach the Global Settlement Agreement. In addition, the amended petition asserts a claim against Navidea for breach of contract. CRG alleges that Navidea breached the Global Settlement Agreement and its duty of good faith and fair dealing by seeking reconsideration in the original Texas suit, appealing the original Texas suit, and filing the Ohio suit. The Company is contesting this issue in the Ohio Court, the Texas Court, and on appeal in Texas. See Note 12.

~~Former CEO Arbitration~~

On May 12, 2016 the Company received a demand for arbitration through the American Arbitration Association, Columbus, Ohio, from Ricardo J. Gonzalez, the Company’s then Chief Executive Officer, claiming that he was terminated without cause and, alternatively, that he resigned in accordance with Section 4G of his Employment Agreement pursuant to a notice received by the Company on May 9, 2016. On May 13, 2016, the Company notified Mr. Gonzalez that his failure to undertake responsibilities assigned to him by the Board of Directors and otherwise work after being ordered to do so on multiple occasions constituted an effective resignation, and the Company accepted that resignation. The Company rejected the resignation of Mr. Gonzalez pursuant to certain provisions in Section 4G of his Employment Agreement. Also, the Company notified Mr. Gonzalez that, alternatively, his failure to return to work after the expiration of the cure period provided in his Employment Agreement constituted cause for his termination under his Employment Agreement. Mr. Gonzalez was seeking severance and other amounts claimed to be owed to him under his Employment Agreement. In response, the Company filed counterclaims against Mr. Gonzalez alleging malfeasance by Mr. Gonzalez in his roleawarded as Chief Executive Officer. Mr. Gonzalez withdrew his claim for additional severance pursuant to his Employment Agreement, and the Company withdrew its counterclaims. On May 12, 2017, the Company received a ruling in favor of Mr. Gonzalez finding that he was terminated by the Company without cause on April 7, 2016. Mr. Gonzalez was awarded salary, bonus, and benefits in the aggregate amount of $481,039 plus interest, attorneys’damages reasonable attorneys' fees ~~and other costs. The arbitration award is final and binding on the parties. The Company paid an aggregate of $617,880 to Mr. Gonzalez on May 16, 2017.~~

~~FTI Consulting, Inc. Litigation~~

On October 11, 2016, FTI Consulting, Inc. (“FTI”) commenced an action against the Company in the Supreme Court of the State of New York, County of New York, seeking damages in excess of $782,600 comprised of: (i) $730,264 for investigative and consulting services FTI alleges to have provided to the Company pursuant to an Engagement Agreement between FTI and the Company, and (ii) in excess of $52,337 for purported interest due on unpaid invoices, plus attorneys’ fees, costs and expenses. On November 14, 2016, the Company filed an Answer and Counterclaim denying the allegations of the Complaint and seeking damages on its Counterclaim, in an amount, if any, to be determined at trial. The case is set for a bench trial ~~for intentional overbilling by FTI. On February 7, 2017,~~on May 17, 2022. CRG has made a ~~preliminary conference was held by~~claim of approximately $2.8 million in attorneys' fees they contend they are entitled to in connection with the Court at which time a scheduling order governing discovery was issued. On June 26, 2017, the Company and FTI entered into a settlement agreement. According to FTI, as of June 2017, FTI was owed $862,165 including interest charges and legal fees. Under the termsalleged breaches of the ~~settlement agreement,~~agreements. Navidea contends CRG have received payments in excess of the ~~Company paid~~amounts owed under the CRG Loan Agreement and are not entitled to an ~~aggregate~~award of ~~$435,000~~attorney’s fees. Discovery is ongoing and a motion to ~~FTI on June 30, 2017.~~amend the interlocutory partial summary judgment is pending. The amount of ultimate liability, if any, with respect to this action is unknown. See Note 2.

~~Sinotau~~Platinum Litigation – ~~Tc99m~~ ~~Tilmanocept~~

~~On February 1,~~In November 2017, Navidea filed suit against Sinotau in the U.S. District Court for the Southern District of Ohio. The Company's complaint included claims seeking a declaration of the rights and obligations of the parties to an agreement regarding rights for the Tc99m tilmanocept product in China and other claims. The complaint sought a temporary restraining order (“TRO”) and preliminary injunction to prevent Sinotau from interfering with the Company’s Asset Sale to Cardinal Health 414. On February 3, 2017, the Court granted the TRO and extended it until March 6, 2017. The Asset Sale closed on March 3, 2017. On March 6, the Court dissolved the TRO as moot. Sinotau also filed a suit against the Company and Cardinal Health 414 in the U.S. District Court for the District of Delaware on February 2, 2017. On July 12, 2017, the District of Delaware case was transferred to the Southern District of Ohio. On July 27, 2017 the Ohio Court determined that both cases in the Southern District of Ohio are related and the case was stayed for 60 days pending settlement discussions. On February 8, 2018, Navidea and Sinotau executed an amendment to the agreement, modifying certain terms of the agreement and effectively resolving the legal dispute. On February 17, 2018, Navidea and Sinotau executed a Settlement Agreement and Mutual Release, and on February 20, 2018, Navidea and Sinotau voluntarily dismissed their legal cases.

~~Platinum-Montaur Life Sciences LLC~~

~~On November 2, 2017,~~ Platinum-Montaur commenced an action against the Company in the Supreme Court of the State of New York, County of New York (the “New York Supreme Court”), seeking damages of approximately $1.9 million purportedly due as of March 3, 2017, plus interest accruing thereafter. The claims asserted were for breach of contract and unjust enrichment in connection with funds received by the Company under the Platinum Loan Agreement. The action was subsequently removed to the United States District Court for the Southern District of New York on December 6, 2017. An initial pretrial conference was held on January 26, 2018 and a follow up status conference was held on March 9, 2018, during which the District Court set a briefing schedule and determined that Navidea’s motion to dismiss was due on April 6, 2018. The Company filed its motion to dismiss in advance of the filing deadline.York. On October 31, 2018, the District Court granted judgment for Navidea and dismissed all claims in the case. The District Court stated that Platinum-Montaur had no standing to assert any contractual interest in funds that might be due under the Platinum Loan Agreement. The District Court also disagreed with Platinum-Montaur’s claim of unjust enrichment on similar grounds and found that Platinum-Montaur lacked any sufficient personal stake to maintain claims against Navidea. The claims against Navidea were dismissed without prejudice on the grounds of lack of standing to pursue the claims asserted.

On November 30, 2018, Platinum-Montaur filed a notice of appeal with the United States Court of Appeals for the Second Circuit (the “Second Circuit”) claiming that the District Court erred in dismissing Platinum-Montaur’s claims for breach of contract and unjust enrichment. On January 22, 2019, Platinum-Montaur filed its brief in the Second Circuit, asking the Second Circuit to reverse the District Court and remand the case to the District Court for further proceedings. The Second Circuit held oral argument in this matter on September 5, 2019. On ~~February 26,~~November 25, 2019, ~~the Company filed its brief in the Second Circuit. It is not known at this time whether~~ the Second Circuit ~~will hold oral argument on this matter or when~~issued a decision which remanded the case to the District Court for further consideration of whether the District Court had jurisdiction over the case following removal from the New York Supreme Court. The Second Circuit ~~will render its decision.~~did not address the merits of Platinum-Montaur’s allegations against Navidea. By agreement of the parties, the case was remanded from the District Court to the New York Supreme Court. Navidea filed a Motion to Dismiss on June 4, 2020, and on September 2, 2020, the New York Supreme Court granted the Motion to Dismiss. Platinum-Montaur filed a Notice of Appeal of the New York Supreme Court’s decision on September 23, 2020 and the appeal was docketed with the Appellate Department-First Division. Platinum-Montaur perfected an appeal of the judgment in favor of the Company on or about June 28, 2021. In February 2022, Platinum and the Company settled their dispute and Platinum’s lawsuit was dismissed. See Note ~~12.~~2.

Goldberg Agreement and Litigation

~~Effective~~ In August ~~14,~~ 2018, Dr. ~~Michael~~ Goldberg resigned from his positions as an executive officer and a director of Navidea. In connection with Dr. Goldberg’s resignation, Navidea and Dr. Goldberg entered into ~~the~~an Agreement ~~with the intent of entering into one or more additional Definitive Agreements,~~(the “Goldberg Agreement”) which set forth the terms of the separation from service. ~~The~~Among other things, the Goldberg Agreement ~~provides~~provided that Dr. Goldberg ~~will~~would be entitled to receive a severance of $978,000 payable in equal installments over two years, along with a one-time payment of approximately $35,000 which represents the cost of continuing his existing health care coverage for a period of 16 months. The Agreement also provides that Dr. Goldberg will be entitled to 23.5 million1,175,000 shares of ~~common stock of Navidea,~~our Common Stock, representing in part payment of accrued bonuses and payment of the balance of the Platinum ~~Note.~~debt. A portion of the ~~23.5 million~~1,175,000 shares to be issued to Dr. Goldberg ~~will~~would be held in escrow for up to 18 months in order to reimburse Navidea in the event that Navidea is obligated to pay any portion of the Platinum ~~Note~~debt to a party other than Dr. Goldberg. Further, the Goldberg Agreement ~~provides~~provided that the Company’s subsidiary, MT, ~~will~~would redeem all of Dr. Goldberg’s preferred stock and issue to Dr. Goldberg super voting common stock equal to 5% of the outstanding shares of MT. On In November ~~20,~~ 2018, the Company issued ~~18.5 million~~925,000 shares of ~~common stock of Navidea~~our Common Stock to Dr. Goldberg, ~~5.0 million~~250,000 of which were placed in escrow in accordance with the Goldberg Agreement. ~~As of the date of filing this Annual Report on Form 10-K, the Definitive Agreements have not yet been signed.~~

F- 22

On February 11, 2019, Dr. Goldberg represented to the MT Board that he had, without MT Board or shareholder approval, created a subsidiary of MT, transferred all of the assets of MT into the subsidiary, and then issued himself stock in the subsidiary. On February 19, 2019, Navidea notified MT that it was terminating the sublicense in accordance with its terms, effective March 1, 2019, ~~because MT became insolvent in violation of the sublicense agreement.~~due to MT’s insolvency. On February 20, 2019, the MT Board ~~of Directors of MT~~ removed Dr. Goldberg as President and Chief Executive Officer of MT and from any other office of MT to which he may have been appointed or in which he was serving. Dr. Goldberg remains a member of the MT Board, together with ~~Michael Rice~~John K. Scott, Jr. and Dr. ~~Claudine Bruck.~~Michael S. Rosol. Mr. ~~Rice and Dr. Bruck remain members~~Scott is also the Vice Chair of the ~~board~~Board of ~~directors~~Directors of Navidea. ~~The~~On or about February 17, 2022, the Joint Official Liquidators and Foreign Representatives of PPVA executed the necessary paperwork to transfer its preferred stock in MT ~~Board then appointed Mr. Latkin~~ to ~~serve as President and Chief Executive Officer of MT.~~Navidea.

New York Litigation Involving Dr. Goldberg

On February 20, 2019, Navidea filed a complaint against Dr. Goldberg in the United States District Court, ~~for the~~ Southern District of New York, alleging breach of the Goldberg Agreement, as well as a breach of the covenant of good faith and fair dealing and to obtain a declaratory judgment that Navidea’s performance under the Goldberg Agreement is excused and that Navidea is entitled to terminate the Goldberg Agreement as a result of Dr. Goldberg’s actions. ~~Also~~On April 26, 2019, Navidea filed an amended complaint against Dr. Goldberg which added a claim for breach of fiduciary duty seeking damages related to certain actions Dr. Goldberg took while CEO of Navidea. On June 13, 2019, Dr. Goldberg answered the amended complaint and asserted counterclaims against Navidea and third-party claims against MT for breach of the Goldberg Agreement, wrongful termination, injunctive relief, and quantum meruit.

On December 26, 2019, the District Court ruled on several motions related to Navidea and MT and Dr. Goldberg that substantially limited the claims that Dr. Goldberg can pursue against Navidea and MT. Specifically, the District Court found that certain portions of Dr. Goldberg’s counterclaims against Navidea and third-party claims against MT failed to state a claim upon which relief can be granted. Additionally, the District Court ruled that actions taken by Navidea and MT, including reconstituting the MT board of directors, replacing Dr. Goldberg with Mr. Latkin as Chief Executive Officer of MT, terminating the sublicense between Navidea and MT, terminating certain research projects, and allowing MT intellectual property to revert back to Navidea, were not breaches of the Goldberg Agreement.

The District Court also rejected Dr. Goldberg’s claim for wrongful termination as Chief Executive Officer of MT. In addition, the District Court found that Dr. Goldberg lacked standing to seek injunctive relief to force the removal of Dr. Claudine Bruck and Michael Rice from MT’s Board of Directors, to invalidate all actions taken by the MT Board on or after November 29, 2018 (the date upon which Dr. Bruck and Mr. Rice were appointed by Navidea to the Board of MT), or to reinstate the terminated sublicense between Navidea and MT.

In addition, the District Court found Navidea’s breach of fiduciary duty claim against Dr. Goldberg for conduct occurring more than three years prior to the filing of the complaint to be time-barred and that Dr. Goldberg is entitled to an advancement of attorneys’ fees solely with respect to that claim. To avoid further litigation expenses, the Company agreed to indemnify Dr. Goldberg solely with respect to the breach of fiduciary duty claim.

On January 31, 2020, Goldberg filed a motion for leave to amend his complaint to add back in claims for breach of contract, breach of the implied covenant of good faith and fair dealing, quantum meruit and injunctive relief. On April 1, 2020, the District Court denied Dr. Goldberg’s motion for leave to amend in its entirety.

On January 27, 2020, Dr. Goldberg filed a motion seeking additional advancement from Navidea for fees in connection with the New York Action and the Delaware Action. Navidea opposed the motion and the District Court referred the matters to a Magistrate Judge. On July 9, 2020, the Magistrate Judge issued her Report and Recommendation which recommended that: (1) the District Court decline to exercise jurisdiction over Dr. Goldberg’s motion as it pertained to expenses and fees incurred in defense of the Delaware Action; (2) the District Court decline to award any fees to Dr. Goldberg for the breach of fiduciary duty without additional motion practice on the issue; (3) the District Court find that Dr. Goldberg is entitled to advancement of his expenses and fees reasonably incurred in the defense of the remainder of the New York action subject to Dr. Goldberg’s posting of an undertaking; and (4) establish a protocol by which Dr. Goldberg could establish the amounts due for advancement.

On August 24, 2020, in connection with Dr. Goldberg’s motion for advancement, the District Court adopted the Magistrate Judge’s report and recommendation and found that while Dr. Goldberg was not being granted advancement of fees and expenses incurred in connection with either the Delaware Action or the assertion of third-party claims against MT, the Court ruled that Dr. Goldberg was entitled to advancement for the defense of the remaining claims asserted against him by Navidea in the New York action. The Court adopted a protocol by which additional motion practice will occur to determine the appropriate amount of fees to be advanced. Once that decision is made by the Magistrate Judge, subject to review by the District Court, Navidea will need to advance those fees to Dr. Goldberg conditioned upon Dr. Goldberg agreeing to pay those fees back to Navidea if it is determined that he is not entitled to indemnification.

F- 23

On May 27, 2021, the District Court ordered that: (1) Dr. Goldberg be awarded $14,955 for indemnification for his attorneys’ fees for his defense of the breach of fiduciary duty claim; (2) Dr. Goldberg be advanced $1,237.50 for his attorneys’ fees subject to repayment; (3) Navidea should not be required to indemnify or advance any of the costs sought by Dr. Goldberg; (4) Dr. Goldberg is not entitled to advancement for the prosecution of his counterclaims and third-party claims; (5) Dr. Goldberg’s motion to hold Navidea in contempt be denied; and (6) Navidea should not be required to advance any additional fees or costs unless Dr. Goldberg presents his time records and costs in compliance with the District Court’s orders. The Company has made the payments ordered by the District Court.

On August 6, 2021, the Company moved for reconsideration of its obligations to advance fees in light of the Delaware Court’s decision dated June 23, 2021 (described below). On October 14, 2021, the Magistrate Judge recommended that Navidea’s motion for reconsideration be denied. On March 7, 2022, the District Court adopted the Report and Recommendation in part and permitted Dr. Goldberg to seek advancement for his fees incurred in defense of his claims since September 1, 2020. Dr. Goldberg’s application is due on or before April 8, 2022.

Delaware Litigation Involving Dr. Goldberg

On February 20, 2019, MT initiated a suit against Dr. Goldberg in the Court of Chancery of the State of Delaware (the “Delaware Court”), alleging, among other things, breach of fiduciary duty as a director and officer of MT and conversion, and to obtain a declaratory judgment that the transactions Dr. Goldberg caused MT to ~~enter into~~effect are void. On ~~March 13,~~June 12, 2019, the Delaware Court found that Dr. Goldberg’s actions were not authorized in compliance with the Delaware General Corporate Law. Specifically, the Delaware Court found that Dr. Goldberg’s creation of ~~Chancery entered an order maintaining status quo, which provided, among other things, that MT’s board~~a new subsidiary of ~~directors may authorize any act or transaction on behalf of~~MT and the ~~Company, and that without prior written authorization of the MT board,~~purported assignment by Dr. Goldberg ~~shall not hold himself out as CEO~~ of ~~MT or purport~~MT’s intellectual property to ~~act or authorize any action~~that subsidiary were void. The Delaware Court’s ruling follows the order on ~~behalf~~May 23, 2019 in the case, in which it found Dr. Goldberg in contempt of ~~MT except as authorized~~its prior order holding Dr. Goldberg responsible for the payment of MT’s fees and costs to cure the damages caused by ~~the MT board.~~Dr. Goldberg’s contempt.

On ~~March 7, 2019,~~June 23, 2021, the Delaware Court ruled in favor of MT and against Dr. Goldberg, ~~filed a complaint~~finding that Dr. Goldberg breached his fiduciary duties to MT. Specifically, the Delaware Court ruled: “Dr. Goldberg attempted to take for himself that which belonged to [MT]. In doing so, he breached his duty of loyalty to [MT] stockholders. [MT] was absolutely justified in bringing this action to remedy (in this case undo) the harm caused by Dr. Goldberg’s misconduct.” The Delaware Court disagreed with MT’s arguments regarding damages and, other than awarding nominal damages, declined to award additional relief beyond that which it had previously granted. With respect to MT’s claim for conversion, the Delaware Court found that the claim was not supported because “Dr. Goldberg confirmed that he currently does not own or possess any intellectual property related to either Navidea or [MT]” and that “any IP Dr. Goldberg created while at Navidea or any of its subsidiaries was and remains the property of Navidea and its subsidiaries.” In addition, the Delaware Court denied Dr. Goldberg’s motion to hold MT’s directors and CEO in contempt, denied Dr. Goldberg’s motion to dismiss the lawsuit against ~~Navidea~~him, and granted MT’s motion to dismiss Dr. Goldberg’s petition to remove MT’s board members. On December 9, 2021, Dr. Goldberg was ordered to reimburse MT in the ~~United States District Court for~~amount of $66,796.33 and has paid that amount to MT. Neither party has appealed the ~~Southern District of New York. The Complaint alleges a breach of contract claim against both Navidea~~Delaware Court’s decision and ~~MT for failure to pay to Dr. Goldberg funds allegedly due to him under~~ the Platinum Note. The Complaint further alleges a breach of contract claim against Navidea due to Navidea’s failure to issue 23.5 million shares to Dr. Goldberg, to issue MT Super Voting Common Stock, by removing Dr. Greene from the MT Board of Directors, by appointing Mr. Rice and Dr. Bruck to the MT Board of Directors, and by terminating Dr. Goldberg as CEO of MT.Delaware Court’s decisions are now final. See Note ~~22.~~2.

NYSE American Continued Listing Standards

On ~~August 14, 2018,~~ January 28, 2022, the Company received a ~~notification (the “Deficiency Letter”)~~deficiency letter from the NYSE American LLC stating that Navidea was not in compliance with a certain NYSE American continued listing ~~standards~~standard relating to stockholders’ equity. Specifically, the ~~Deficiency Letter~~deficiency letter stated that ~~Navidea is~~ we are not in compliance with Section 1003(a)(ii) of the NYSE American Company Guide, which requires an issuer to have stockholders’ equity of $4.0 million or more if it has reported losses from continuing operations and/or net losses in three of its four most recent fiscal years. The Deficiency Letter noted that Navidea had stockholders’ equity of $2.1 million as of June 30, 2018, and has reported net losses in four of its five most recent fiscal years ended December 31, 2017.

On October 25, 2018, the Company received a notification (the “Acceptance Letter”) from the NYSE American that the Company’s plan to regain compliance was accepted. The Acceptance Letter also stated that the NYSE American had inadvertently omitted an additional deficiency from the Deficiency Letter. Specifically, the Deficiency Letter should have stated that Navidea is not in compliance with Section 1003(a)1003(a)(iii) of the NYSE American Company Guide, which requires an issuer to have stockholders’ equity of ~~$6.0~~$6.0 million or more if it has reported losses from continuing operations and/or net losses in its five most recent fiscal years. The ~~Acceptance Letter~~deficiency letter noted that ~~Navidea~~we had stockholders’ equity of ~~$2.1~~$4.1 million as of ~~June~~September 30, ~~2018,~~ 2021, and ~~has~~ reported net losses from continuing operations ~~and/or net losses~~ in ~~its~~ our five most recent fiscal years ended December 31, ~~2017.~~2020.

F- 24

~~The Company must provide quarterly updates~~We submitted a plan to the NYSE American ~~staff (the “Staff”) concurrent with its interim/annual SEC filings. If Navidea fails~~on February 28, 2022 advising of actions we have taken and will take to regain compliance with the ~~stockholders’ equity~~continued listing standards by ~~February 14, 2020,~~July 28, 2023. If our plan is not accepted, or if we do not make progress consistent with the plan, or if we otherwise fail to regain compliance by the deadline, the NYSE American may commence delisting procedures.

~~In addition, the Deficiency Letter stated~~ There is no assurance that the Staff determined that the Company’s securities have been selling for a low price per share for a substantial period of time and, pursuant to Section 1003(f)(v) of the NYSE American Company Guide, Navidea’swe will meet continued listing is predicated on it effecting a reverse stock split of its common stock, par value $0.001 per share (“Common Stock”) or otherwise demonstrating sustained price improvement within a reasonable period of time. The Staff initially granted Navidea a plan period through February 14, 2019 to regain compliance with Section 1003(f)(v) by effecting a reverse stock split or otherwise demonstrating sustained price improvement.standard.

In August 2018, Navidea’s stockholders voted to approve a potential amendment to the Company’s amended and restated certificate of incorporation to effect a reverse split of the Company’s common stock, as determined by the Board of Directors at its discretion, of a ratio of not less than one-for-five and not more than one-for-twenty.

On January 28, 2019, the Company received a notice from the NYSE American that they had granted the Company an extension until March 31, 2019 to regain compliance with Section 1003(f)(v) of the NYSE American’s continued listing standards. Navidea must regain compliance with the price standard by that date in order to be considered for continued trading through the end of February 14, 2020.

~~In accordance with ASC Topic 450,~~ ~~Contingencies~~, we make a provision for a liability when it is both probable that a liability has been incurred and the amount of the loss can be reasonably estimated. Although the outcome of any litigation is uncertain, in our opinion, the amount of ultimate liability, if any, with respect to these actions, will not materially affect our financial position.

16.13.

Equity Instruments

Preferred Stock and Common Stock: In December 2019, the Company executed a Stock Purchase Agreement with the investors named therein. Pursuant to the Stock Purchase Agreement, the investors agreed to purchase approximately 2.1 million shares of the Company’s Common Stock ~~Issued:~~ ~~During September 2018,~~in a private placement for aggregate gross proceeds to the Company of approximately $1.9 million. Of this amount, approximately $1.1 million was received during 2019 and the remaining $812,000 of proceeds were received and the related Common Stock was issued in January 2020.

In February 2020, the Company executed agreements with two existing investors to purchase approximately 4.0 million shares of the Company’s Common Stock for aggregate gross proceeds to Navidea of approximately $3.4 million. The entire $3.4 million was received and the related 4,020,588 shares of Common Stock were issued during 2020.

On May 6, 2020, the Company entered into a Stock Purchase Agreement and Letter of Investment Intent with Keystone pursuant to which the Company agreed to issue to Keystone 420,000 shares of newly-designated Series C Preferred Stock for an aggregate purchase price of $4.2 million. Pursuant to the Stock Purchase Agreement, Keystone agreed to purchase shares of Series C Preferred Stock in amounts to be determined by Keystone in one or more closings on or before November 6, 2020, provided that all of the Series C Preferred Stock must be purchased by such date. Holders of the Series C Preferred Stock had the option to convert some or all of the Series C Preferred Stock into shares of the Company’s Common Stock at a 10% discount to market (the “Series C Conversion Shares”), provided that the Company could not issue such Series C Conversion Shares in excess of 19.99% of the number of shares of Common Stock outstanding as of the date of the investment (the “Series C Exchange Cap”) without shareholder approval, which the Company was not required to seek. The entire $4.2 million was received and the related 420,000 shares of Series C Preferred Stock were issued during 2020. In accordance with current accounting guidance, the Company recorded a deemed dividend of approximately $467,000 related to the BCF of the 420,000 shares of Series C Preferred Stock that were issued during the year ended December 31, 2020. These 420,000 shares were subsequently converted into 1,425,076 shares of Common Stock during 2020.

On August 9, 2020, Company entered into a binding MOU with Jubilant. The MOU outlines the terms and framework for a potential Exclusive License and Distribution Agreement for Navidea’s Tc99m-Tilmanocept Rheumatoid Arthritis diagnostic application in the United States, Canada, Mexico, and Latin America. In connection with the MOU, the Company entered into a Stock Purchase Agreement with Jubilant, pursuant to which Jubilant purchased 209,205 shares of Common Stock for gross proceeds of $1.0 million in exchange for exclusivity of negotiations while due diligence efforts are completed. The investment was priced “at market,” which was the closing price of Navidea’s Common Stock on the NYSE American on the trading day immediately preceding the investment. See Note 2.

On August 30, 2020, the Company entered into a Common Stock Purchase Agreement with each of the Investors named therein, pursuant to which the Investors agreed to purchase from the Company, up to $25.0 million in shares of the Company’s Common Stock. The initial closing of the sale and purchase of the Common Stock (the “Initial Closing”) was required to occur within forty-five (45) business days after the date on which the NYSE American approved the Company’s listing application for the Common Stock. The Investors agreed to purchase an aggregate of 1,000,000 shares of Common Stock at the Initial Closing, at a purchase price of $5.00 per share. Subsequent closings of the sale and purchase of the Common Stock (each a “Subsequent Closing”) were to occur from time to time after the Initial Closing on such dates and times as agreed upon by the Company and the Investors, but in any event no later than ninety (90) business days after the Initial Closing; provided that the closing price of the Common Stock on the NYSE American exchange shall have closed at or above $5.00 for five consecutive trading days. The Investors were to purchase the Common Stock at such Subsequent Closing at a price per share equal to market value within the meaning of Section 713 of the NYSE American Company Guide; provided that in no event would the Investors be obligated to purchase Common Stock at a Subsequent Closing at a price greater than $5.75 per share. The Company had the right to terminate the Common Stock Purchase Agreement upon written notice to the Investors if (a) the Initial Closing had not occurred within ninety (90) days of the date of the agreement or (b) if the Investors have not purchased an aggregate of $25.0 million in Common Stock as of the date that was ninety (90) business days after the Initial Closing. Notwithstanding the foregoing, no Investor was obligated to purchase any Common Stock if such shares proposed to be purchased, when aggregated with all other shares of Common Stock then owned beneficially by such Investor and its affiliates, would have resulted in the beneficial ownership by such Investor and its affiliates of more than 4.99% of the then issued and outstanding shares of Common Stock. One of the Company’s existing investors, John K. Scott, Jr., was a party to the Common Stock Purchase Agreement and agreed to purchase $25,000 of Common Stock, which amount was received and the related 5,000 shares of Common Stock were issued during 2020. In accordance with current accounting guidance, the remaining $4.975 million of stock subscriptions receivable was included in common stock subscriptions receivable on the consolidated balance sheet as of December 31, 2020. During the second quarter of 2021, the Company determined that it was unlikely that the remaining $4.975 million would ever be collected. Accordingly, the common stock subscription receivable was reversed from the consolidated balance sheet during the second quarter of 2021. On December 14, 2021, the Company terminated the Common Stock Purchase Agreement. See Note 2.

F- 25

On August 31, 2020, the Company entered into the Series D Preferred Stock Purchase Agreement with Keystone pursuant to which the Company agreed to issue to Keystone 150,000 shares of newly-designated Series D Preferred Stock for an aggregate purchase price of $15.0 million. Pursuant to the Series D Preferred Stock Purchase Agreement, Keystone agreed to purchase Series D Preferred Stock in amounts to be determined by Keystone in one or more closings during the nine-month period following the date on which the prospectus supplement to register the underlying Common Stock was filed with the SEC, provided that all of the Series D Preferred Stock must be purchased by such date. Holders of the Series D Preferred Stock have the option to convert some or all of the Series D Preferred Stock into shares of the Company’s Common Stock at a 10% discount to market (the “Series D Conversion Shares”), provided that the Company may not issue such Series D Conversion Shares in excess of 19.99% of the number of shares of Company common stock outstanding as of the date of the investment without shareholder approval, which the Company is not required to seek. The Series D Preferred Stock is convertible into a maximum of 5,147,000 shares of Common Stock.

In the event of the liquidation or dissolution of the Company, after payment of the debts and other liabilities of the Company, the holders of Series D Preferred Stock then outstanding shall be entitled to receive, out of the assets of the Company and before any payment may be made to the holders of Common Stock or any other junior stock, an amount per share of Series D Preferred Stock calculated by taking the total amount available for distribution to holders of all outstanding Common Stock before deduction of any preference payments for the Series D Preferred Stock, divided by the total of (x) all of the then outstanding shares of Common Stock plus (y) all of the shares of Common Stock into which the outstanding shares of Series D Preferred Stock can be converted, and then (z) multiplying the sum so obtained by the number of shares of Common Stock into which such share of Series D Preferred Stock could then be converted.

Of the $15.0 million, approximately $1.8 million was received and the related 17,750 shares of Series D Preferred Stock were issued during 2020. The Company recorded a deemed dividend of approximately $197,000 related to the BCF of the 17,750 shares of Series D Preferred Stock that were issued during 2020. These 17,750 shares were subsequently converted into 827,280 shares of Common Stock during 2020. An additional $2.9 million was received and the related 29,250 shares of Series D Preferred Stock were issued during the period beginning on January 1, 2021 and ending on March 26, 2021, the date of filing of the 2020 Annual Report on Form 10-K. These 29,250 shares of Series D Preferred Stock were subsequently converted into 1,375,089 shares of Common Stock during the period beginning on January 1, 2021 and ending on March 26, 2021. In accordance with current accounting guidance, $2.9 million of stock subscriptions receivable was included in stock subscriptions and other receivables, and approximately $10.3 million was included in preferred stock subscriptions receivable in the consolidated balance sheet as of December 31, 2020.

Through July 7, 2021, Keystone purchased 72,500 shares of Series D Preferred Stock pursuant to the Series D Preferred Stock Purchase Agreement for an aggregate purchase price of $7.25 million, which were subsequently converted into 3,778,789 shares of Common Stock through December 31, 2021. Of those amounts, 17,750 shares of Series D Preferred Stock were purchased and converted into 827,280 shares of Common Stock in 2020, and 54,750 shares of Series D Preferred Stock were purchased and converted into 2,951,509 shares of Common Stock in 2021. On July 8, 2021, the Company entered into the Series D Amendment with Keystone pursuant to which Keystone purchased 22,077 shares of Series D Preferred Stock for an aggregate purchase price of approximately $2.2 million. After purchasing the 22,077 shares, Keystone has no further right or obligation to purchase shares of Series D Preferred Stock. Accordingly, the Series D Preferred Stock subscription receivable was reduced to $0 on the condensed consolidated balance sheet as of December 31, 2021. Including the purchases pursuant to the Series D Amendment, Keystone’s purchases of Series D Preferred Stock pursuant to the Series D Purchase Agreement during the year ended December 31, 2021 totaled 76,827 shares of Series D Preferred Stock for an aggregate purchase price of approximately $7.7 million. The Series D Amendment also contains a customary mutual release provision. As of December 31, 2021, 22,077 shares of Series D Preferred Stock remain outstanding. See Note 2.

On March 2, 2021, the Company entered into a Series E Preferred Stock Purchase Agreement with an existing accredited investor, John K. Scott, Jr. pursuant to which the Company issued to ~~the investor~~Mr. Scott in a private placement transaction 50,000 shares of Series E Preferred Stock for an aggregate purchase price of $5.0 million.

Under the Series E Preferred Stock Purchase Agreement, Mr. Scott was granted a right of first offer with respect to future issuances of Company securities (the ~~“Private Placement”~~“Right of First Offer”) ~~18,320,610 shares (the “Securities”)~~; provided, however, that in no event shall Mr. Scott have such right if the acquisition of any of such securities would result in Mr. Scott beneficially holding more than 33.33% of the Company’s ~~common stock, par value $0.001~~outstanding Common Stock on an as-converted basis, as determined in accordance with Section 13(d) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), and the rules thereunder (the “Share Cap”). In the event that Mr. Scott does not exercise the Right of First Offer, the Company will then be entitled to offer and sell the new securities to any third party at a price not less than, and upon terms no more favorable to the offeree than, those offered to Mr. Scott (a “Third Party Offering”). Pursuant to the Series E Preferred Stock Purchase Agreement, Mr. Scott also has the option to purchase up to 33.33% of the new securities offered in a Third-Party Offering at the same price and upon the terms available to the other purchaser(s) (the “Preemptive Right”); provided, however, that in no event may Mr. Scott acquire new Company securities in a Third-Party Offering to the extent the acquisition thereof would violate the Share Cap. The Right of First Offer and the Preemptive Right expired on December 31, 2021.

F- 26

In connection with the private placement, the Company entered into a registration rights agreement (the “Registration Rights Agreement”), pursuant to which, among other things, the Company prepared and filed with the Securities and Exchange Commission (the “SEC”) a registration statement on Form S-1 to register for resale the maximum number of Series E Conversion Shares (as defined below) issuable upon conversion of the Series E Preferred Stock. In the event that both (i) the number of shares of Common Stock beneficially held by Mr. Scott falls below 20% of the outstanding Common Stock on an as-converted basis, as determined in accordance with Section 13(d) of the Exchange Act and the rules thereunder, and (ii) Mr. Scott is an affiliate (as that term is defined under Rule 144) at the time of the Reload Request (as defined below), the Company, upon written request from Mr. Scott (the “Reload Request”), will be required prepare and file with the SEC one, and only one, additional registration statement covering the resale of those shares of Common Stock owned by Mr. Scott as of the date of the Reload Request that, as of such time, are not registered for resale under the Securities Act of 1933, as amended (the “Securities Act”). The securities issued in the offering have not been registered under the Securities Act, and until so registered the securities may not be offered or sold absent registration or availability of an applicable exemption from registration.

Except with respect to transactions which may adversely affect any right, preference, privilege or voting power of the Series E Preferred Stock, the Series E Preferred Stock has no voting rights. Whenever the Company’s Board of Directors declares a dividend on Common Stock, each record holder of a share of Series E Preferred Stock on the record date set by the Board of Directors will be entitled to receive an amount equal to such dividend declared on one share of Common Stock multiplied by the number of shares of Common Stock (the “Series E Conversion Shares”) into which such share of Series E Preferred Stock could be converted on the record date, without regard to any conversion limitations in the Series E Preferred Certificate of Designation of Preferences, Rights and Limitations (the “Series E Preferred Certificate”). Holders of the Series E Preferred Stock may convert some or all of the Series E Preferred Stock into Series E Conversion Shares at a fixed price of $2.30 per Series E Conversion Share, provided that the aggregate number of Series E Conversion Shares issued pursuant to the Series E Preferred Certificate cannot exceed the Share Cap without shareholder approval, which the Company is not required to seek. The Company has the right to redeem any outstanding shares of Series E Preferred Stock at a price of $110 per share ~~(the “Common Stock”),~~ at ~~a purchase price~~any time on or prior to the one-year anniversary of ~~$3.0 million (the “Purchase Price”). The Company plans to use~~ the issuance date, payable in cash. See Note 2.

Navidea has used the net proceeds from ~~the Private Placement~~these transactions to fund its R&D programs, including continued advancement of its two Phase 2b and Phase 3 clinical trials of Tc99m tilmanocept in patients with rheumatoid arthritis, and for general working capital purposes ~~including, without limitation, research and development,~~ and other operating expenses. See Note 2.

During November 2018, the Company issued 18,500,000 shares of common stock to Dr. Goldberg in connection with the August 2018 Agreement. Of those shares, 5,000,000 are being held in escrow pursuant to the Agreement. See Note 15.

During the years ended December 31, 2018 and 2017, we issued 1,118,760 and 710,353 shares of our common stock valued at $317,000 and $369,000, respectively, to our employees as payments in lieu of cash for their 2017, 2016 and 2015 bonuses.

During the years ended December 31, 2018 and 2017, we issued 94,684 and 105,308 shares of our common stock as matching contributions to our 401(k) Plan which were valued at $36,000 and $54,000, respectively.

During the year ended December 31, 2017, we issued 16,406 shares of our common stock valued at $10,500 to certain members of our Board of Directors as payment in lieu of cash for their retainer fees. We did not make any such stock payments to our directors during the year ended December 31, 2018.

During the years ended December 31, 2021 and 2020, we issued 30,018 and 32,651 shares of Common Stock as matching contributions to our 401(k) Plan which were valued at $76,846 and $39,834, respectively.

During the year ended December 31, 2020, we issued 94,159 shares of our Common Stock valued at $172,000 to our full-time employees as partial payment in lieu of cash for their 2019 bonuses. NaN such stock bonus payments were made during the year ended December 31, 2021.

Stock Warrants: At As of December 31, ~~2018,~~ 2021, there are ~~16.4 million~~972,324 outstanding warrants ~~outstanding~~ to purchase ~~our common stock.~~Common Stock. The warrants are exercisable at prices ranging from ~~$0.01~~$0.20 to ~~$2.50~~$49.80 per share with a weighted average exercise price per share of ~~$1.15.~~$17.97. The warrants have remaining outstanding terms ranging from ~~0.7~~0.2 to ~~16.6~~13.6 years.

The following table summarizes information about our outstanding warrants at as of December 31, ~~2018:~~2021.

	Exercise Price			Number of Warrants		Expiration Date	Exercise Price			Number of Warrants		Expiration Date
Series HH		2.49			301,205	June 2023	$	49.80			15,060	6/25/2023
Series KK		1.918			391,032	March 2021
Series LL		0.01			4,365,280	August 2035		0.20			218,264	8/20/2035
Series MM		2.50			150,000	September 2019
Series MM		2.50			150,000	October 2019
Series NN		1.50			11,000,000	March 2022		30.00			550,000	3/3/2022
Series OO								0.9375			189,000	6/13/2024
Total warrants	$	1.15	*		16,357,517		$	17.97	*		972,324

Weighted average exercise price.

In addition, ~~at December 31, 2018, there are~~ 300 warrants ~~outstanding~~ to purchase MT Common ~~Stock. The warrants are exercisable~~Stock at $2,000 per ~~share.~~

~~In January 2017, Dr. Goldberg, then the Company’s President and CEO, exercised 5,411,850 of his Series LL warrants~~share expired in ~~exchange for 5,411,850 shares of our common stock, resulting in proceeds to the Company of $54,119.~~

In March 2017, in connection with the Asset Sale, the Company granted to each of Cardinal Health 414 and UCSD, a five-year Series NN warrant to purchase up to 10 million shares and 1 million shares, respectively, of the Company’s common stock at an exercise price of $1.50 per share, each of which warrant is subject to anti-dilution and other customary terms and conditions. The fair value of the Series NN warrants was calculated using the Black-Scholes model using our five-year historical weekly volatility of 77.0% and a risk-free rate equal to the five-year treasury constant maturity rate of 2.0%. The Series NN warrants granted to Cardinal Health 414 had an estimated fair value of $3.3 million, which was recorded as a reduction of the gain on sale in the consolidated statement of operations for the year ended December 31, 2017. The Series NN warrants granted to UCSD had an estimated fair value of $334,000, which was recorded as an intangible asset related to the UCSD license in the consolidated balance sheet during the year ended December 30, 2017.2020.

Common Stock Reserved: As of December 31, ~~2018,~~ 2021, we have reserved ~~19,515,686~~1,892,114 shares of authorized ~~common stock~~Common Stock for the exercise of all outstanding stock options and ~~warrants.~~ warrants, 1,368,211 shares for the issuance of Common Stock upon conversion of Series D Preferred Stock, 2,173,913 shares for the issuance of Common Stock upon conversion of Series E Preferred Stock and 49,242 shares to be issued to certain directors who elected to defer receipt of both cash stock for director fees until at least July 1, 2022. An additional ~~5,000,000~~250,000 shares of ~~common stock~~Common Stock have been reserved for issuance to Dr. Goldberg related to the ~~August 2018~~Goldberg Agreement. See Note ~~15.~~11.

F- 27

17.14.

Income Taxes

As of December 31, ~~2018~~ 2021 and ~~2017,~~2020, our deferred tax assets (“DTAs”) were approximately ~~$41.6~~$48.5 million and ~~$39.7~~$45.8 million, respectively. The components of our deferred tax assets are summarized ~~as follows:~~in the following table.

As of December 31,

2018

2017

Deferred tax assets:

Net operating loss carryforwards
$ 29,597,313 $ 29,570,581
R&D credit carryforwards
9,067,874 10,043,714
AMT credit carryforward
621,240 1,229,979
Stock compensation
375,731 576,024
Intangibles
550,797 591,651
Gain/loss from discontinued operations
— (2,510,699
)
Disallowed interest expense
878,929 —
Temporary differences
480,888 207,447
Deferred tax assets before valuation allowance
41,572,772 39,708,697
Valuation allowance
(40,951,532
)
(38,478,718
)
Net deferred tax assets
$ 621,240 $ 1,229,979

	As of December 31,
	2021			2020
Deferred tax assets:
Net operating loss carryforwards	$	36,793,074		$	34,365,098
R&D credit carryforwards		9,501,299			9,301,709
Stock compensation		481,098			419,654
Intangibles		567,213			616,926
Disallowed interest expense		851,247			852,338
Temporary differences		305,974			267,312
Deferred tax assets before valuation allowance		48,499,905			45,823,037
Valuation allowance		(48,499,905	)		(45,823,037	)
Net deferred tax assets	$	0		$	0

Current accounting standards require a valuation allowance against DTAs if, based on the weight of available evidence, it is more likely than not that some or all of the DTAs may not be realized. Due to the uncertainty surrounding the realization of these DTAs in future tax returns, all of the DTAs have been fully offset by a valuation allowance at as of December 31, ~~2018~~ 2021 and ~~2017 except the alternative minimum tax (“AMT”) credit carryforward amount described below.~~2020.

In assessing the realizability of DTAs, management considers whether it is more likely than not that some portion or all of the DTAs will not be realized. The ultimate realization of DTAs is dependent upon the generation of future taxable income during the periods in which those temporary differences become deductible. Management considers the scheduled reversal of deferred tax liabilities (including the impact of available carryback and carryforward periods) and projected future taxable income in making this assessment. Based upon the level of historical taxable income and projections for future taxable income over the periods in which the DTAs are deductible, management believes it is more likely than not that the Company will not realize the benefits of these deductible differences or tax carryforwards as of December 31, ~~2018, except for the AMT credit carryforward.~~2021.

The Tax Cuts and Jobs Act (the “Tax Act”) was signed into law on December 22, 2017. The Tax Act reduced the U.S. federal corporate tax rate from 35% to 21%, effective January 1, 2018. Consequently, we recorded a decrease related to DTAs of $26.4 million with a corresponding net adjustment to a valuation allowance of $26.4 million for the year ended December 31, ~~2017.~~ 2018. The Tax Act ~~repeals~~repealed the AMT for corporations, and ~~permits~~permited any existing AMT credit carryforwards to be used to reduce the regular tax obligation in 2018,2019 and 2020. Companies may continue using AMT credits to offset any regular income tax liability in years 2018 through 2020, with 50% of remaining AMT credits refunded in each of the 2018,2019 and 2020 tax years, and all remaining credits refunded in tax year 2021. This results in full realization of an existing AMT credit carryforward irrespective of future taxable income. The CARES Act was signed into law on March 27, 2020 and allowed an acceleration of the full remaining AMT credit carryforward as a refund in the current year. Accordingly, the Company ~~recorded~~filed for and received the refund of all $621,000 of AMT credit carryforwards, ~~of $1.2 million~~plus interest, in other noncurrent assets in the consolidated balance sheet as of December 31, 2017. The Company reclassified 50% of the $1.2 million noncurrent DTA to income tax receivable, which is included in prepaid and other current assets as of December 31, 2018.June 2020.

As of December 31, ~~2018~~ 2021 and ~~2017,~~2020, we had U.S. net operating loss carryforwards of approximately ~~$130.9~~$164.1 million and ~~$131.8~~$153.3 million, respectively. Of those amounts, ~~$15.1~~$14.9 million relates to stock-based compensation tax deductions in excess of book compensation expense (“APIC NOLs”) as of December 31, ~~2018,~~ 2021, that will be credited to additional paid-in capital when such deductions reduce taxes payable as determined on a "with-and-without" basis. Accordingly, these APIC NOLs will reduce federal taxes payable if realized in future periods, but NOLs related to such benefits are not included in the table above. As of December 31, 2017, we adopted ASU ~~2016-09~~2016-09 and thereby eliminated all APIC NOLs with a full offset to a valuation allowance.

As of December 31, ~~2018~~ 2021 and ~~2017,~~2020, we also had state net operating loss carryforwards of approximately ~~$20.3 million and $20.4 million, respectively.~~$20.1 million. The state net operating loss carryforwards will begin expiring in 2032.

At As of December 31, ~~2018~~ 2021 and ~~2017,~~2020, we had U.S. R&D credit carryforwards of approximately ~~$8.7~~$9.1 million and ~~$9.7~~$8.9 million, respectively.

There were no expirations of U.S. NOL carryforwards during ~~2018~~2021 or ~~2017.~~2020. U.S. R&D credit carryforwards of ~~$1.2 million~~$0 and $72,000 expired during ~~2018. There were no expirations of U.S. R&D credit carryforwards during 2017.~~ 2021 and 2020, respectively.

F- 28

The details of our U.S. net operating loss and federal R&D credit carryforward amounts and expiration dates are summarized ~~as follows:~~in the following table.

As of December 31, 2018

Generated

Expiration

U.S. Net
Operating
Loss
Carryforwards

U.S. R&D
Credit
Carryforwards

1999

2019
$ — $ 130,359
2000

2020
— 71,713
2001

2021
— 39,128
2002

2022
— 5,350
2003

2023
— 2,905
2004

2024
— 22,861
2005

2025
— 218,332
2006

2026
— 365,541
2007

2027
— 342,898
2008

2028
— 531,539
2009

2029
— 596,843
2010

2030
— 1,094,449
2011

2031
— 1,950,744
2012

2032
18,684,249 468,008
2013

2033
37,450,522 681,772
2014

2034
34,088,874 816,116
2015

2035
25,073,846 492,732
2016

2036
15,581,209 262,257
2017

2037
— 387,892
2018 2038 — 197,547
Total carryforwards
$ 130,878,700 $ 8,678,986

During the year ended December 31, 2017, Cardiosonix recorded losses for financial reporting purposes of $5,000. As of December 31, 2016, Cardiosonix had tax loss carryforwards in Israel of approximately $7.7 million. Under Israeli tax law, net operating loss carryforwards do not expire. Due to the uncertainty surrounding the realization of the related deferred tax assets in future tax returns and the Company’s intent to dissolve Cardiosonix in the near term, all of the deferred tax assets were fully offset by a valuation allowance at December 31, 2016. Cardiosonix was legally dissolved in September 2017 and as a result we eliminated all tax loss carryforwards with a full offset to a valuation allowance.

		As of December 31, 2021
Generated	Expiration	U.S. Net Operating Loss Carryforwards		U.S. R&D Credit Carryforwards
2001	2021	$	—	$	39,128
2002	2022		—		5,350
2003	2023		—		2,905
2004	2024		—		22,861
2005	2025		—		218,332
2006	2026		—		365,541
2007	2027		—		342,898
2008	2028		—		531,539
2009	2029		—		596,843
2010	2030		—		1,094,449
2011	2031		—		1,950,744
2012	2032		18,898,490		468,008
2013	2033		37,450,522		681,772
2014	2034		34,088,874		816,116
2015	2035		25,073,846		492,732
2016	2036		15,581,209		262,257
2017	2037		—		387,892
2018	N/A		—		197,547
2019	N/A		11,245,808		213,065
2020	N/A		11,018,478		222,842
2021	N/A		10,746,123		238,717
Total carryforwards		$	164,103,350	$	9,112,411

Under Sections 382 and 383 of the ~~IRC~~Internal Revenue Code (“IRC”) of 1986, as amended, the utilization of U.S. net operating loss and R&D tax credit carryforwards may be limited under the change in stock ownership rules of the IRC. The Company completed a Section 382 analysis ~~in 2017~~ through December 31, 2021 and ~~does not believe~~believes that a Section 382 ownership change has ~~occurred since then that would impact utilization of the Company’s net operating loss and R&D tax credit carryforwards.~~not occurred.

Reconciliations between the statutory federal income tax rate and our effective tax rate for continuing operations are ~~as follows:~~presented in the following table.

2018

2017

Amount

%

Amount

%

Benefit at statutory rate
$ (3,383,491
)
(21.0
)%
$ (6,048,423
)
(34.0
)%
Adjustments to valuation allowance
2,458,580 15.3
%
(26,080,051
)
(146.6
)%
Adjustments to R&D credit carryforwards
975,840 6.1
%
(291,745
)
(1.6
)%
Tax law changes
— — 28,731,045 161.5
%
Permanent items and other
(60,682
)
(0.3
)%
(373,315
)
(2.2
)%
Benefit per financial statements
$ (9,753 ) $ (4,062,489
)

~~See Note 1(p).~~

	2021						2020
	Amount			%			Amount			%
Benefit at statutory rate	$	(2,460,126	)		(21.0	)%	$	(2,390,972	)		(21.0	)%
Adjustments to valuation allowance		2,676,868			22.9	%		2,521,625			22.1	%
Adjustments to R&D credit carryforwards		(199,589	)		(1.7	)%		(151,129	)		(1.3	)%
Permanent items and other		(1,110	)		(0.1	)%		20,476			0.2	%
Provision (benefit) per financial statements	$	16,043					$	0

18.15.

Segments

We report information about our operating segments using the “management approach” in accordance with current accounting standards. This information is based on the way management organizes and reports the segments within the enterprise for making operating decisions and assessing performance. Our reportable segments are identified based on differences in products, services and markets served. There were no0 inter-segment sales. We manage our business based on two primary types of drug products: (i) diagnostic substances, including Tc99m tilmanocept and other diagnostic applications of our Manocept platform, ~~and NAV4694 (sublicensed in April 2018),~~ and (ii) therapeutic development programs, including therapeutic applications of our Manocept ~~platform and all development programs undertaken by MT.~~platform.

F- 29

The information in the following tables is derived directly from each reportable segment’s financial reporting. ~~Certain revenue and expense amounts in the year ended December 31, 2017 have been reclassified to discontinued operations. See Note 3.~~

Year Ended December 31, 2018

Diagnostics

Therapeutics

Corporate

Total

Royalty revenue
$ 15,347 $ — $ — $ 15,347
License revenue
307,174 — — 307,174
Grant and other revenue
494,997 351,833 — 846,830
Total revenue
817,518 351,833 — 1,169,351
Cost of revenue
96,636 — — 96,636
Research and development expenses
3,064,115 1,157,766 — 4,221,881
Selling, general and administrative expenses, excluding depreciation and amortization ^(a)
— 78,606 7,469,144 7,547,750
Depreciation and amortization ^(b)
— — 150,385 150,385
Loss from operations ^(c)
(2,343,233
)
(884,539
)
(7,619,529
)
(10,847,301
)
Other expense ^(d)
— — (5,321,270
)
(5,321,270
)
Benefit from income taxes
1,413 534 7,806 9,753
Loss from continuing operations
(2,341,820
)
(884,005
)
(12,932,993
)
(16,158,818
)
Income from discontinued operations, net of tax effect
1,449 — — 1,449
Gain on sale of discontinued operations, net of tax effect
43,053 — — 43,053
Net loss
(2,297,318
)
(884,005
)
(12,932,993
)
(16,114,316
)
Total assets, net of depreciation and amortization:

United States
$ 91,425 24,763 6,878,129 6,994,317
International
14,330 381 14,711
Capital expenditures
— — 46,192 46,192

Year Ended December 31, 2021	Diagnostics			Therapeutics			Corporate			Total
Royalty revenue	$	0		$	0		$	0		$	0
License revenue		45,615			0			0			45,615
Grant and other revenue		485,898			0			0			485,898
Total revenue		531,513			0			0			531,513
Research and development expenses, excluding depreciation and amortization		4,488,177			653,733			0			5,141,910
Selling, general and administrative expenses, excluding depreciation and amortization ⁽¹⁾		0			4,438			7,368,623			7,373,061
Depreciation and amortization ⁽²⁾		24,162			0			52,792			76,954
Loss from operations ⁽³⁾		(3,980,826	)		(658,171	)		(7,421,415	)		(12,060,412	)
Other income ⁽⁴⁾		0			0			345,524			345,524
Provision for income taxes		(5,452	)		(901	)		(9,690	)		(16,043	)
Net loss		(3,986,278	)		(659,072	)		(7,085,581	)		(11,730,931	)
Total assets, net of depreciation and amortization:
United States	$	107,931		$	0		$	6,326,031		$	6,433,962
International		210,281			0			590			210,871
Capital expenditures		0			0			25,218			25,218

Year Ended December 31, 2017	Diagnostics			Therapeutics			Corporate			Total
Year Ended December 31, 2020													Diagnostics			Therapeutics			Corporate			Total
Royalty revenue	$	9,126		$	—		$	—		$	9,126		$	7,995		$	0		$	0		$	7,995
License revenue		100,000			—			—			100,000			110,730			0			0			110,730
Grant and other revenue		1,506,232			195,079			—			1,701,311			482,221			314,067			0			796,288
Total revenue		1,615,358			195,079			—			1,810,437			600,946			314,067			0			915,013
Cost of revenue		3,651			—			—			3,651			1,048			0			0			1,048
Research and development expenses, excluding depreciation and amortization		3,784,255			729,587			—			4,513,842
Research and development expenses														4,593,459			336,728			0			4,930,187
Selling, general and administrative expenses, excluding depreciation and amortization ^(a)(1)		—			34,484			10,895,301			10,929,785			299,959			800			6,323,807			6,624,566
Depreciation and amortization ^(b)(2)		—			—			240,166			240,166			10,068			0			60,325			70,393
Loss from operations ^(c)(3)		(2,172,548	)		(568,992	)		(11,135,467	)		(13,877,007	)		(4,303,588	)		(23,461	)		(6,384,132	)		(10,711,181	)
Other income (expense) ^(d)		—			—			(3,912,679	)		(3,912,679	)
Benefit from income taxes		496,127			129,936			3,436,426			4,062,489
Loss from continuing operations		(1,676,421	)		(439,056	)		(11,611,720	)		(13,727,197	)
Income from discontinued operations, net of tax effect		88,673,053			—			—			88,673,053
Net income (loss)		86,996,632			(439,056	)		(11,611,720	)		74,945,856
Other expense ⁽⁴⁾														0			0			(10,510	)		(10,510	)
Net loss														(4,303,588	)		(23,461	)		(6,394,642	)		(10,721,691	)
Total assets, net of depreciation and amortization:
United States	$	13,065,871		$	49,001		$	7,634,237		$	20,749,109		$	139,121		$	0		$	7,416,106		$	7,555,227
International		30,476			—			1,851			32,327			202,791			0			0			202,791
Capital expenditures		—			—			33,690			33,690			120,810			0			15,071			135,881

^(a)(1)

General and administrative expenses, excluding depreciation and amortization, represent costs that relate to the general administration of the Company and as such are not currently allocated to our individual reportable ~~segments. Marketing~~segments, other than those expenses directly incurred by Navidea Europe, Navidea UK and ~~selling expenses are allocated to our individual reportable segments.~~MT.

^(b)(2)

Depreciation and amortization isare reflected in selling, general and administrative expenses ($~~150,385~~76,954 and ~~$240,166~~$70,393 for the years ended December 31, ~~2018~~ 2021 and ~~2017,~~2020, respectively).

^(c)(3)

Loss from operations does not reflect the allocation of certain selling, general and administrative expenses, excluding depreciation and amortization, to our individual reportable ~~segments.~~segments, other than those expenses directly incurred by Navidea Europe, Navidea UK and MT.

^(d)(4)

Amounts consist primarily of gain on extinguishment of debt, interest income and interest expense, ~~changes in fair value of financial instruments, and losses on debt extinguishment,~~ which are not currently allocated to our individual reportable segments.

19.16.

Material Agreements

~~Supply Agreements:~~ In November 2009, we entered into a manufacture and supply agreement with Reliable Biopharmaceutical Corporation (“Reliable”) for the manufacture and supply of the Tc99m tilmanocept drug substance. The initial ten-year term of the agreement expires in November 2019, with options to extend the agreement for successive three-year terms. Either party had the right to terminate the agreement upon mutual written agreement, or upon material breach by the other party if not cured within 60 days from the date of written notice of the breach. Total purchases under the manufacture and supply agreement were $0 for the years ended December 31, 2018 and 2017. Upon closing of the Asset Sale to Cardinal Health 414, our contract and open purchase order with Reliable were transferred to Cardinal Health 414.

In September 2013, we entered into a manufacturing services agreement with OSO BioPharmaceuticals Manufacturing, LLC (“OsoBio”) for contract pharmaceutical development, manufacturing, packaging and analytical services for Tc99m tilmanocept. Either party had the right to terminate the agreement upon mutual written agreement, or upon material breach by the other party if not cured within 60 days from the date of written notice of the breach. During the term of agreement, OsoBio was the primary supplier of manufacturing services for Tc99m tilmanocept. In consideration for these services, the Company paid a unit pricing fee. In addition, the Company also paid OsoBio a fee for regulatory and other support services. Total purchases under the manufacturing services agreement were $0 and $250,000 for the years ended December 31, 2018 and 2017, respectively. Upon closing of the Asset Sale to Cardinal Health 414, our contract and open purchase orders with OsoBio were transferred to Cardinal Health 414.

Also in September 2013, we completed a service and supply master agreement with Gipharma S.r.l. (“Gipharma”) for process development, manufacturing and packaging of reduced-mass vials to be sold in the EU. The agreement had an initial term of three years and automatically renewed for an additional one-year periods. In consideration for these services, the Company paid fees as defined in the agreement. Total purchases under the service and supply master agreement were $0 and $14,000 for the years ended December 31, 2018 and 2017, respectively. Following the transfer of the Tc99m tilmanocept Marketing Authorization to SpePharm, our contract with Gipharma was transferred to SpePharm.

b.a)

Research and Development ~~Agreements~~Agreements: In January 2002, we completed a license agreement with ~~UCSD~~the University of California, San Diego (“UCSD”) for the exclusive world-wide rights to Tc99m ~~tilmanocept.~~ tilmanocept for use in lymphatic mapping. The license agreement was effective until the later of the expiration date of the longest-lived underlying patent. In July 2014, we amended the license agreement to extend the agreement until the third anniversary of the expiration date of the longest-lived underlying patent. Under the terms of the license agreement, UCSD granted us the exclusive rights to make, use, sell, offer for sale and import licensed products as defined in the agreement and to practice the defined licensed methods during the term of the agreement. We could also sublicense the patent rights, subject to certain sublicense terms as defined in the agreement. In consideration for the license rights, we agreed to pay UCSD a license issue fee of $25,000 and license maintenance fees of $25,000 per year. We also agreed to make payments to UCSD upon successfully reaching certain clinical, regulatory and cumulative sales milestones, and a royalty on net sales of licensed products subject to a $25,000 minimum annual royalty. In addition, we agreed to reimburse UCSD for all patent-related costs and to meet certain diligence targets.

F- 30

In connection with the sale of the rights to sell Tc99m tilmanocept in the United States, Canada and Mexico to Cardinal Health 414, the Company amended and restated its Tc99m tilmanocept license agreement with UCSD pursuant to which UCSD granted a license to the Company to exploit certain intellectual property rights owned by UCSD and, separately, Cardinal Health 414 entered into a license agreement with UCSD pursuant to which UCSD granted a license to Cardinal Health 414 to exploit certain intellectual property rights owned by UCSD for Cardinal Health 414 to sell Tc99m tilmanocept in the United States, Canada and Mexico. Total costs related to the UCSD license agreement for net sales and royalties of Tc99m tilmanocept outside the ~~Territory~~United States, Canada and Mexico were $4,000 and $1,000 in 2021and ~~$4,000~~2020, respectively, and were recorded as a reduction in ~~2018~~license revenue and ~~2017,~~in cost of revenue, respectively. Total costs related to the UCSD license agreement for annual maintenance fees, milestones and patent-related costs were $21,000 and $34,000 in 2021 and 2020, respectively, and were recorded in ~~cost of revenue.~~R&D expenses.

In connection with the March 2017 closing of the Asset Sale to Cardinal Health 414, the Company amended and restated its Tc99m tilmanocept license agreement with UCSD pursuant to which UCSD granted a license to the Company to exploit certain intellectual property rights owned by UCSD and, separately, Cardinal Health 414 entered into a license agreement with UCSD pursuant to which UCSD granted a license to Cardinal Health 414 to exploit certain intellectual property rights owned by UCSD for Cardinal Health 414 to sell the Product in the Territory. Pursuant to the Purchase Agreement, in 2017 the Company granted to UCSD a five (5)-year warrant to purchase up to 1 million shares of the Company’s common stock, par value $.001 per share, at an exercise price of $1.50 per share. Total costs related to the amended and restated UCSD license agreement for annual maintenance fees and patent-related costs were $35,000 and $34,000 in 2018 and 2017, respectively, and were recorded in research and development expenses.

In July 2014, the Company executed an expanded license agreement for the exclusive world-wide rights to all diagnostic and therapeutic uses of tilmanocept (other than Tc99m tilmanocept). The license agreement is effective until the third anniversary of the expiration date of the longest-lived underlying patent. Under the terms of the license agreement, UCSD has granted us the exclusive rights to make, use, sell, offer for sale and import licensed products as defined in the agreement and to practice the defined licensed methods during the term of the agreement. We may also sublicense the patent rights, subject to certain sublicense terms as defined in the agreement. As consideration for the license rights, we agreed to pay UCSD a license issue fee of $25,000 and license maintenance fees of $25,000 per year. We also agreed to make payments to UCSD upon successfully reaching certain clinical, regulatory and cumulative sales milestones, and a royalty on net sales of licensed products subject to a $25,000 minimum annual royalty. In addition, we agreed to reimburse UCSD for all patent-related costs and to meet certain diligence targets. Total costs related to the UCSD license agreement for tilmanocept were $250,000 and $253,000 in 2018 and 2017, respectively, and were recorded in research and development expenses.

In December 2011, we executed a license agreement with AstraZeneca AB for NAV4694, a proprietary compound that is primarily intended for use in diagnosing Alzheimer’s disease and other CNS disorders. The license agreement is effective until the later of the tenth anniversary of the first commercial sale of NAV4694 or the expiration of the underlying patents. Under the terms of the license agreement, AstraZeneca granted us an exclusive worldwide royalty-bearing license for NAV4694 with the right to grant sublicenses. In consideration for the license rights, we paid AstraZeneca a license issue fee of $5.0 million upon execution of the agreement. We also agreed to pay AstraZeneca up to $6.5 million in contingent milestone payments based on the achievement of certain clinical development and regulatory filing milestones, and up to $11.0 million in contingent milestone payments due following receipt of certain regulatory approvals and the initiation of commercial sales of the licensed product. In addition, we agreed to pay AstraZeneca a royalty on net sales of licensed and sublicensed products. Total costs (adjustments) related to the AstraZeneca license agreement were $0 and $(70,000) in 2018 and 2017, respectively, and were recorded in research and development expenses.

In July 2014, the Company executed an expanded license agreement for the exclusive world-wide rights to all diagnostic and therapeutic uses of tilmanocept (other than Tc99m tilmanocept used in lymphatic mapping). The license agreement is effective until the third anniversary of the expiration date of the longest-lived underlying patent. Under the terms of the license agreement, UCSD has granted us the exclusive rights to make, use, sell, offer for sale and import licensed products as defined in the agreement and to practice the defined licensed methods during the term of the agreement. We may also sublicense the patent rights, subject to certain sublicense terms as defined in the agreement. As consideration for the license rights, we agreed to pay UCSD a license issue fee of $25,000 and license maintenance fees of $25,000 per year. We also agreed to make payments to UCSD upon successfully reaching certain clinical, regulatory and cumulative sales milestones, and a royalty on net sales of licensed products subject to a $25,000 minimum annual royalty. In addition, we agreed to reimburse UCSD for all patent-related costs and to meet certain diligence targets. Total costs related to the UCSD license agreement for tilmanocept were $25,000 and $275,000 in 2021 and 2020, respectively, and were recorded in R&D expenses.

~~Employment Agreements:~~Separation Agreement: ~~As of December 31, 2018, we had~~Effective July 27, 2020 through October 24, 2021, Mr. Latkin was employed under an employment agreement that provided for an annual base salary of $490,000. On November 23, 2021, Mr. Latkin signed a Separation Agreement and General Release (the “Separation Agreement”) in connection with ~~one~~his resignation from his positions as Chief Executive Officer, Chief Operating Officer and Chief Financial Officer, and as a director, on October 24, 2021 (the “Separation Date”). Pursuant to the Separation Agreement, among other things, the Company agreed to provide Mr. Latkin with certain separation benefits, commencing on the “Effective Date,” defined as the eighth day after Mr. Latkin signs, without revoking, the Separation Agreement. These separation benefits include continued payment of ~~our senior officers. The employment agreement contains termination and/~~Mr. Latkin’s base salary of $490,000, less all relevant taxes and other withholdings, on the following basis: (i) for 12 months, 100% of his base salary, minus an aggregate $24,000 deducted monthly pro rata for reimbursement of Mr. Latkin’s attorney fees which were paid by the Company, and (ii) for 10 months following the expiration of the first12-month period, 50% of his base salary. On the Effective Date, each of Mr. Latkin’s unvested stock options vested, and all of his vested stock options (covering 69,918 shares) and previously unvested options (covering 333,332 shares) may be exercised by Mr. Latkin on or ~~change in control provisions that would entitle~~before the ~~officer to 4.25 times his annual salary~~earlier of the fifth anniversary of the Separation Date and ~~vest~~the original expiration date. On the Effective Date, each of Mr. Latkin’s 33,333 outstanding unvested restricted stock units became fully vested, and ~~options~~all of such restricted stock units were settled within thirty days after the Separation Date, less applicable withholding in shares of common stock. The Company also agreed to ~~purchase common stock if there is a termination without cause or change~~reimburse Mr. Latkin for expenses incurred pursuant to Company policy. For purposes of assistance provided in ~~control~~certain litigation matters, the Company agreed to pay Mr. Latkin $250 per hour, subject to certain limitations. Mr. Latkin will also be entitled to receive, subject to his timely execution and non-revocation of the Separation Agreement, a payment equal to up to one percent of total capital raised during the twenty-two months following the Separation Date through one of two investment banking firms introduced to the Company ~~(as defined)~~by Mr. Latkin, less relevant taxes and ~~his employment terminates. As of December 31, 2018, our maximum contingent liability under this agreement in such an event is approximately $2.0 million. The employment agreement~~withholdings and subject to certain payment terms. In addition, Mr. Latkin and the Company generally ~~also provides for severance, disability~~released each other from any and ~~death benefits.~~all claims each may have against the other.

20.17.

Employee Benefit Plan

We maintain an employee benefit plan under Section ~~401(k)~~401(k) of the ~~IRC.~~IRC (the “401(k) Plan”). The ~~plan~~401(k) Plan allows employees to make contributions and we may, but are not obligated to, match a portion of the employee’s contribution with our ~~common stock,~~Common Stock, up to a defined maximum. We also pay certain expenses related to maintaining the ~~plan.~~401(k) Plan. Beginning January 1, 2021, the Company’s Board of Directors increased the Company match rate from 40% of employee contributions to the 401(k) Plan up to 5% of the employee’s salary, to 100% of employee contributions to the 401(k) Plan up to 6% of the employee’s salary. We recorded expenses related to ~~our 401(k) plan~~the 401(k) Plan of ~~$40,000~~$148,000 and ~~$12,000~~$49,000 during ~~2018~~2021 and ~~2017, respectively.~~2020, respectively

F- 31

21.18.

Supplemental Disclosure for Statements of Cash Flows

~~During 2018 and 2017, we~~We paid interest aggregating ~~$8,000~~$9,000 and ~~$7.4 million,~~$6,000 in 2021 and 2020, respectively. In February 2020, the Company amended its existing office lease and recognized a right-of-use lease asset in exchange for a lease liability of $100,432. During ~~2017,~~2020, we issued ~~1 million Series NN warrants to UCSD with an estimated fair value of $334,000. During 2018 and 2017, we issued 94,684 and 105,308~~94,159 shares of our common stock valued at $172,000 to our employees as partial payment in lieu of cash for their 2019 bonuses. During 2021 and 2020, we issued 30,018 and 32,651 shares of Common Stock, respectively, as matching contributions to our ~~401(k)~~401(k) Plan which were valued at ~~$36,000~~$76,846 and ~~$54,000,~~$39,834, respectively. In November ~~2018,~~ 2021, we prepaid ~~$393,000~~$566,000 of insurance premiums through the issuance of a note payable to IPFS with an interest rate of ~~5.1%~~4.36%. In November ~~2017,~~ 2020, we prepaid ~~$396,000~~$442,000 of insurance premiums through the issuance of a note payable to IPFS with an interest rate of ~~4.0%~~3.5%. ~~As discussed~~During 2020, 411,000 Series OO warrants to purchase the Company’s common stock were exercised on a cashless basis in ~~Note 9, the liability~~exchange for ~~the additional $200,000~~issuance of ~~investments made by Platinum was reclassified to additional paid-in-capital in January 2017. As discussed in Note 15, in November 2018,~~300,595 shares of Navidea Common Stock. During 2020, the Company ~~issued 18.5 million~~recorded a deemed dividend of approximately $467,000 related to the BCF on 420,000 shares of ~~common stock~~Series C Preferred Stock, and 420,000 shares of ~~Navidea~~Series C Preferred Stock were converted into 1,425,076 shares of Common Stock. Also during 2020, the Company recorded a deemed dividend of approximately $197,000 related to ~~Dr. Goldberg,~~the BCF on 17,750 shares of ~~which approximately 16.4 million~~Series D Preferred Stock, and 17,750 shares ~~valued at $3.2 million~~of Series D Preferred Stock were ~~applied as payment~~converted into 827,280 shares of ~~the Platinum debt, including principal and accrued interest of $2.2 million and loss on extinguishment of debt of $1.0 million.~~Common Stock.

22.19.

Subsequent Events

On February 11, 2019, Dr. Goldberg represented to the MT Board that he had, without MT Board or shareholder approval, created a subsidiary of MT, transferred all of the assets of MT into the subsidiary, and then issued himself stock in the subsidiary. On February 19, 2019, Navidea notified MT that it was terminating the sublicense effective March 1, 2019 because MT became insolvent in violation of the sublicense agreement. On February 20, 2019, the Board of Directors of MT removed Dr. Goldberg as President and Chief Executive Officer of MT and from any other office of MT to which he may have been appointed or in which he was serving. Dr. Goldberg remains a member of the MT Board, together with Michael Rice and Dr. Claudine Bruck. Mr. Rice and Dr. Bruck remain members of the board of directors of Navidea. The ~~MT Board then appointed Mr. Latkin to serve as President and Chief Executive Officer of MT.~~

On March 7, 2019, Dr. Goldberg filed a complaint against Navidea and MT in the United States District Court for the Southern District of New York. The Complaint alleges a breach of contract claim against both Navidea and MT for failure to pay to Dr. Goldberg funds allegedly due to him under the Platinum Note. The Complaint further alleges a breach of contract claim against Navidea due to Navidea’s failure to issue 23.5 million shares to Dr. Goldberg, to issue MT Super Voting Common Stock, by removing Dr. Greene from the MT Board of Directors, by appointing Mr. Rice and Dr. Bruck to the MT Board of Directors, and by terminating Dr. Goldberg as CEO of MT. See Note 15.

~~Except as described above, the~~ Company has evaluated events and transactions subsequent to December 31, ~~2018~~ 2021 and through the date these consolidated financial statements were included in this Annual Report on Form ~~10-K~~10-K and filed with the SEC.

~~F-36~~

Delaware		31-1080091
(State or other jurisdiction of incorporation or organization)		(I.R.S. Employer Identification No.)

4995 Bradenton Avenue, Suite 240, Dublin, Ohio		43017-3552
(Address of principal executive offices)		(~~I.R.S. Employer Identification No.)~~

~~4995 Bradenton Avenue, Suite 240, Dublin, Ohio~~		~~43017-3552~~
~~(Address of principal executive offices)~~		(Zip Code)

Title of Each Class	Trading Symbol(s)	Name of Each Exchange on which Registered
Common Stock, par value $.001 per share	~~NYSE American~~
~~(Title of Class)~~NAVB	~~(Name of Each Exchange on Which Registered)~~NYSE American

Large accelerated filer	☐	Accelerated filer	☐
Non-accelerated filer	☒	Smaller reporting company	☒
		Emerging growth company	☐

	Cumulative Total Return as of December 31,
	2016		2017		2018		2019		2020		2021
Navidea Biopharmaceuticals	$	100.00	$	56.25	$	15.63	$	9.84	$	16.80	$	7.81
Russell 3000		100.00		118.85		110.54		142.09		168.04		209.36
NASDAQ Biotechnology		100.00		121.06		109.77		136.56		171.64		170.55

	Cumulative Total Return as of December 31,
	2013		2014		2015		2016		2017		2018
Navidea Biopharmaceuticals	$	100.00	$	91.30	$	64.25	$	30.92	$	17.39	$	4.83
Russell 3000		100.00		110.45		108.83		120.16		142.81		132.83
NASDAQ Biotechnology		100.00		134.10		149.42		117.02		141.66		128.45

PART I

Item 1	Business	1

Item 1A	Risk Factors	12

Item 1B	Unresolved Staff Comments	26

Item 2	Properties	26

Item 3	Legal Proceedings	26

Item 4	Mine Safety Disclosure	26

PART II		27

Item 5	Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities	27

Item 6	Selected Financial Data	28

Item 7	Management’s Discussion and Analysis of Financial Condition and Results of Operations	28

Item 7A	Quantitative and Qualitative Disclosures About Market Risk	34

Item 8	Financial Statements and Supplementary Data	34

Item 9	Changes in and Disagreements with Accountants on Accounting and Financial Disclosure	34

Item 9A	Controls and Procedures	34

Item 9B	Other Information	35

Item 9C	Disclosures Regarding Foreign Jurisdictions that Prevent Inspections	35

PART III		36

Item 10	Directors, Executive Officers and Corporate Governance	36

Item 11	Executive Compensation	39

Item 12	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	53

Item 13	Certain Relationships and Related Transactions, and Director Independence	55

Item 14	Principal Accountant Fees and Services	58

PART IV		59

Item 15	Exhibits, Financial Statement Schedules	59

Development Program ^(a)	2018		2017
Manocept Platform ^(b)	$	1,291,796	$	2,140,701
Macrophage Therapeutics ^(b)		1,203,419		853,294
Tc99m Tilmanocept		145,314		236,004
NAV4694 ⁽^c⁾		19,105		(371,588	)

Development Program ^(a)	2021		2020
Manocept Platform – Diagnostics ^(b)	$	2,620,057	$	3,008,463
Manocept Platform – Therapeutics		653,733		337,278
Tc99m Tilmanocept ^(b)		136,941		57,456

	●	pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the Company;

	●	provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with U.S. GAAP and that receipts and expenditures of the company are being made only in accordance with authorization of management and directors of the Company; and

Name	Age		Committee(s)
~~Claudine Bruck, Ph.D.~~ ^(a)Amit Bhalla	6347	Audit
Alexander L. Cappello	66	Audit; Compensation, Nominating and Governance ~~(Chair)~~
~~Adam D. Cutler~~ ^(b)John K. Scott, Jr.	4467	Compensation, Nominating and Governance
Malcolm G. Witter	68	Audit (Chair); Compensation, Nominating and Governance
~~Jed. A. Latkin~~ ^(c)	44		—
~~Y. Michael Rice~~	54		~~Audit; Compensation, Nominating and Governance~~
~~S. Kathryn Rouan, Ph.D.~~ ^(d)	56		~~Compensation, Nominating and Governance~~

	~~(a)~~	~~Dr. Bruck was appointed to the Board of Directors effective March 5, 2018.~~ (Chair)
	~~(b)~~	~~Mr. Cutler was appointed to the Board of Directors effective December 1, 2018.~~
	~~(c)~~	~~Mr. Latkin was appointed to the Board of Directors effective August 14, 2018.~~
	~~(d)~~	~~Dr. Rouan was appointed to the Board of Directors effective December 1, 2018.~~

Name	Age	Position
Michael S. Rosol, Ph.D.	5053	Chief Medical Officer
Michel Mikhail, Ph.D.	67	Chief Regulatory Officer
Erika L. Eves	52	Vice President, Finance and Administration

~~AcelRx~~Actinium Pharmaceuticals, Inc.	~~Idera Pharmaceuticals, Inc.~~Curis	NanoViricides
~~Anthera Pharmaceuticals,~~Adaptimmune Therapeutics	CytoDyn Inc.	~~Immune Design Corporation~~
~~Aradigm Corporation~~	~~Innovation Pharmaceuticals, Inc.~~
~~Argos Therapeutics, Inc.~~	~~Invitae Corporation~~
~~CareDx, Inc.~~	~~Invuity, Inc.~~
~~Cascadian Therapeutics, Inc.~~	~~Lipocine, Inc.~~
~~ContraFect Corporation~~	~~Mirati~~Neoleukin Therapeutics, Inc.
~~Curis,~~Advaxis	CytomX Therapeutics, Inc.	~~Sonoma Pharmaceuticals,~~Northwest Biotherapeutics, Inc.
~~CytoDyn,~~aTyr Pharma Inc.	Fate Therapeutics	OncoSec Medical Incorporated
Avid Bioservices, Inc.	Fortress Biotech	PDL Biopharma
Bellicum Pharmaceuticals, Inc.	Genocea Biosciences, Inc.	Phio Pharmaceuticals Corp.
Calithera Biosciences, Inc.	GeoVax Labs, Inc.	Prothena
CEL-SCI	Idera Pharmaceuticals	Regulus Therapeutics, Inc.
Checkpoint Therapeutics, Inc.	Inovio Pharmaceuticals	Selecta Biosciences, Inc.
ChemoCentryx	Lineage Cell Therapeutics, Inc.	Sorrento Therapeutics, Inc.
~~Endocyte,~~Cidara Therapeutics, Inc.	Lumos Pharma, Inc.	T2 Biosystems, Inc.
~~Genocea Biosciences,~~ContraFect Corporation	Marker Therapeutics, Inc.	~~Utah Medical Products, Inc.~~Ziopharm Oncology
~~iCad, Inc.~~Corvus Pharmaceuticals

Named Executive Officer	Fiscal 2018 Base Salary^(a)		Fiscal 2017 Base Salary^(a)		Change^(b)
Jed A. Latkin ^(c)	$	475,000	$	325,000		46.2	%
Michael M. Goldberg, M.D. ^(d)		400,000		400,000		0.0	%
Frederick O. Cope, Ph.D. ⁽^e⁾		279,130		279,130		0.0	%
Michael S. Rosol, Ph.D. ⁽^f⁾		205,000		—		—

Named Executive Officer	Fiscal 2021 Base Salary^(a)		Fiscal 2020 Base Salary^(a)		Change
Michael S. Rosol, Ph.D. ^(b)	$	240,000	$	225,000		6.7	%
Michel Mikhail, Ph.D. ^(c)		225,000		—		—	%
Erika L. Eves		156,200		156,200		—	%
Jed A. Latkin ^(d)		—		490,000		—	%
Joel H. Kaufman ^(e)		—		230,000		—	%

Named Executive Officer	Fiscal 2022 Base Salary		Fiscal 2021 Base Salary		Change
Michael S. Rosol, Ph.D.	$	240,000	$	240,000		—	%
Michel Mikhail, Ph.D.		225,000		225,000		—	%
Erika L. Eves		156,200		156,200		—	%

Named Executive Officer	Target Cash Bonus (% of Salary)			Target Cash Bonus ($ Amount)
Jed A. Latkin ^(a)		75.0	%	$	356,250
Michael M. Goldberg, M.D. ⁽^b⁾		75.0	%		300,000
Frederick O. Cope, Ph.D. ⁽^c⁾		35.0	%		97,696
Michael S. Rosol, Ph.D. ⁽^d⁾		35.0	%		71,750

Named Executive Officer	Target Cash Bonus (% of Salary)			Target Cash Bonus ($ Amount) (a)
Michael S. Rosol, Ph.D.		35.0	%	$	84,000
Michel Mikhail, Ph.D.		35.0	%		78,750
Erika L. Eves		25.0	%		39,050
Jed A. Latkin		75.0	%		367,500
Joel H. Kaufman		35.0	%		80,500

	The Compensation, Nominating
	and Governance Committee

	~~Claudine Bruck, Ph.D.~~Malcolm G. Witter (Chair)
	~~Adam D. Cutler~~
	~~Y. Michael Rice~~Alexander L. Cappello
	~~S. Kathryn Rouan, Ph.D.~~John K. Scott, Jr.

Named Executive Officer	Year	Salary		Stock Awards		(a) Option Awards		(b) Non-Equity Incentive Plan Compensation		(c) All Other Compensation		Total Compensation
Jed A. Latkin ⁽^d⁾	2018	$	362,500	$	—	$	—	$	271,875	$	5,500	$	639,875
Chief Executive Officer,	2017		316,458		—		125,833		366,653		5,429		814,373
Chief Operating Officer and	2016		163,309		—		39,992		—		—		203,301
Chief Financial Officer

Michael M. Goldberg ⁽^e⁾	2018	$	250,000	$	—	$	—	$	225,000	$	1,017,722	$	1,492,722
President and	2017		427,222		—		—		410,768		8,067		846,057
Chief Executive Officer	2016		83,077		—		—		—		436		83,513

Frederick O. Cope, Ph.D. ⁽^f⁾	2018	$	242,409	$	—	$	—	$	—	$	5,500	$	247,909
Senior Vice President and	2017		279,130		—		—		97,969		6,906		383,732
Chief Scientific Officer	2016		279,130		—		—		54,710		6,735		340,575

Michael S. Rosol, Ph.D. ⁽^g⁾	2018	$	8,542	$	—	$	—	$	2,949	$	—	$	11,491
Chief Medical Officer	2017		—		—		—		—		—		—
	2016		—		—		—		—		—		—

Named Executive Officer	Year	Severance		(a) Reimbursement of Additional Tax Liability Related to Insurance Premiums		(b) 401(k) Plan Employer Matching Contribution		Total All Other Compensation
Jed A. Latkin	2018	$	—	$	—	$	5,500	$	5,500
	2017		—		29		5,400		5,429
	2016		—		—		—		—

Michael M. Goldberg, M.D. ^(c)	2018	$	1,012,552	$	—	$	5,170	$	1,017,722
	2017		—		2,667		5,400		8,067
	2016		—		436		—		436

Frederick O. Cope, Ph.D.	2018	$	—	$	—	$	5,500	$	5,500
	2017		—		1,506		5,400		6,906
	2016		—		1,435		5,300		6,735

Michael S. Rosol, Ph.D.	2018	$	—	$	—	$	—	$	—
	2017		—		—		—		—
	2016		—		—		—		—

	For Cause		Resignation		Death		Disability		Without Cause		End of Term		Change in Control
Cash payments:
Severance ^(a)	$	—	$	—	$	—	$	—	$	633,333	$	—	$	1,741,667
Accrued bonus ^(b)		—		—		—		—		271,875		—		271,875
Disability supplement ⁽^c⁾		—		—		—		235,100		—		—		—
Paid time off ⁽^d⁾		9,135		9,135		9,135		9,135		9,135		9,135		9,135
2018 401(k) match ⁽^e⁾		5,500		5,500		5,500		5,500		5,500		5,500		5,500
Continuation of benefits ⁽^f⁾		—		—		960		960		—		—		—
Stock option vesting acceleration ⁽^g)		—		—		—		—		—		—		—
Total	$	14,635	$	14,635	$	15,594	$	250,694	$	919,843	$	14,635	$	2,028,176

			Estimated Future Payouts Under Non-Equity Incentive Plan Awards (a)				Estimated Future Payouts Under Equity Incentive Plan Awards				All Other Stock Awards: Number of Shares		All Other Option Awards: Number of Securities Underlying		Exercise Price of Option		Grant Date Fair Value of Stock and Option
Named Executive Officer	Grant Date		Threshold		Maximum		Threshold		Maximum		of Stock		Options		Awards		Awards
Jed A. Latkin		N/A	$	—	$	271,875		—		—		—		—	$	—	$	—	(b)

Michael M. Goldberg, M.D.		N/A	$	—	$	225,000		—		—		—		—	$	—	$	—	(c)

Frederick O. Cope, Ph.D.		N/A	$	—	$	—		—		—		—		—	$	—	$	—	(d)

Michael S. Rosol, Ph.D.		N/A	$	—	$	2,949		—		—		—		—		—	$	—	(e)

			Estimated Future Payouts Under Non-Equity Incentive Plan Awards				Estimated Future Payouts Under Equity Incentive Plan Awards				All Other Stock Awards: Number of Shares		All Other Option Awards: Number of Securities Underlying		Exercise Price of Option		Grant Date Fair Value of Stock and Option
Named Executive Officer	Grant Date		Threshold		Maximum		Threshold		Maximum		of Stock		Options		Awards		Awards
Michael S. Rosol, Ph.D.		N/A	$	—	$	84,000		—		—		—		—	$	—	$	—	(a)
	2/15/2021			—		—		—		—		—		25,000		2.56		46,962	(b)
	12/27/2021			—		—		—		—		—		100,000		1.08		86,074	(c)

Michel Mikhail, Ph.D.		N/A		—	$	78,750		—		—		—		—	$	—	$	—	(a)
	11/15/2021			—		—		—		—		—		75,000		1.37		81,579	(b)

Erika L. Eves		N/A	$	—	$	39,050		—		—		—		—	$	—	$	—	(a)
	2/15/2021			—		—		—		—		—		12,500		2.56		23,481	(b)

Jed A. Latkin ^(d)		N/A	$	—	$	367,500		—		—		—		—	$	—	$	—	(a)
	2/15/2021			—		—		—		—		—		100,000		2.56		187,849	(b)

Joel H. Kaufman ^(e)		N/A	$	—	$	80,500		—		—		—		—	$	—	$	—	(a)
	2/15/2021			—		—		—		—		—		25,000		2.56		46,962	(b)

	Option Awards								Stock Awards
	Number of Securities Underlying Unexercised Options (#)									Market Value of Shares of	Equity Incentive Plan Awards
Named Executive Officer	Exercisable		Unexercisable		Option Exercise Price		Option Expiration Date	Note	Number of Shares of Stock that Have Not Vested	Stock that Have Not Vested	Number of Unearned Shares	Market Value of Unearned Shares	Note
Jed A. Latkin		45,000		—	$	1.50	4/20/2026	(a)
		20,000		—	$	1.00	10/14/2026	(b)
		—		333,334	$	0.65	5/4/2027	(c)
		—		333,333	$	0.75	5/4/2027	(d)
		—		333,333	$	1.00	5/4/2027	(e)

Michael M. Goldberg, M.D. (f)

Frederick O. Cope, Ph.D. (g)

Michael S. Rosol, Ph.D. (h)

	Option Awards								Stock Awards
	Number of Securities Underlying Unexercised Options (#)									Market Value of Shares of	Equity Incentive Plan Awards
Named Executive Officer	Exercisable		Unexercisable		Option Exercise Price		Option Expiration Date	Note	Number of Shares of Stock that Have Not Vested	Stock that Have Not Vested	Number of Unearned Shares	Market Value of Unearned Shares	Note
Michael S. Rosol,		6,250		—	$	7.60	1/2/2029	(j)
Ph.D.		8,333		16,667		1.06	2/6/2030	(m)
		—		25,000		2.56	2/15/2031	(p)
		—		100,000		1.08	12/27/2031	(s)

Michel Mikhail,		—		75,000	$	1.37	11/15/2031	(r)
Ph.D.

Erika L. Eves		500		—	$	65.60	2/17/2022	(a)
		625		—		61.60	2/15/2023	(b)
		625		—		35.40	1/28/2024	(c)
		625		—		33.00	3/26/2025	(d)
		1,000		—		10.20	4/25/2027	(g)
		1,200		—		7.20	2/20/2028	(i)
		1,600		800		3.00	2/7/2029	(k)
		2,000		4,000		1.06	2/6/2030	(m)
		—		12,500		2.56	2/15/2031	(p)

Jed A. Latkin		2,250		—	$	30.00	4/20/2026	(e)
		1,000		—		20.00	10/14/2026	(f)
		16,667		—		13.00	10/26/2026	(h)
		16,667		—		15.00	10/26/2026	(h)
		16,666		—		20.00	10/26/2026	(h)
		16,667		—		3.00	10/26/2026	(l)
		16,667		—		6.00	10/26/2026	(l)
		16,666		—		10.00	10/26/2026	(l)
		100,000		—		1.06	10/26/2026	(n)
		100,000		—		4.70	10/26/2026	(o)
		100,000		—		2.56	10/26/2026	(q)

Joel H. Kaufman		—		—	$	—

	(a)
	Fees
	Earned or		(b),(c)		(d),(e)
	Paid in		Option		Stock		All Other		Total
Name	Cash		Awards		Awards		Compensation		Compensation
Claudine Bruck, Ph.D. (f)	$	47,111	$	9,659	$	19,150	$	—	$	75,920
Adam D. Cutler (g)		4,212		—		—		—		4,212
Mark I. Greene, M.D., Ph.D. (h)		36,486		9,226		17,955		—		63,667
Y. Michael Rice		73,750		9,226		17,955		—		100,931
S. Kathryn Rouan, Ph.D. (g)		4,212		—		—		—		4,212
Eric K. Rowinsky, M.D. (i)		45,000		9,226		17,955		—		72,181

Name	Fees Earned or Paid in Cash (a)		Option Awards (b),(c)		Stock Awards (d),(e),(f)		All Other Compensation		Total Compensation
Amit Bhalla ^(g)	$	22,063	$	3,089	$	64,706	$	—	$	89,858
Claudine Bruck, Ph.D. ^(h)		29,228		4,259		20,461		—		53,948
Alexander L. Cappello ⁽ⁱ⁾		44,657		—		57,123		—		101,780
Adam D. Cutler ^(j)		31,250		4,259		5,698		—		41,207
Thomas F. Farb ^(k)		17,775		—		4,920		—		22,695
Y. Michael Rice ^(l)		42,500		4,259		5,698		—		52,457
S. Kathryn Rouan, Ph.D. ^(m)		32,390		4,259		24,963		—		61,612
John K. Scott, Jr. ⁽ⁿ⁾		32,918		—		48,509		—		81,427
Agnieszka Winkler ^(o)		6,801		—		5,160		—		11,961
Malcolm G. Witter		41,490		4,259		68,625		—		114,374

Plan Category	(1) Number of Securities to be Issued Upon Exercise of Outstanding Options, Warrants and Rights		(2) Weighted-Average Exercise Price of Outstanding Options, Warrants and Rights		(3) Number of Securities Remaining Available for Issuance Under Equity Compensation Plans (Excluding Securities Reflected in Column (1))		(1) Number of Securities to be Issued Upon Exercise of Outstanding Options, Warrants and Rights		(2) Weighted-Average Exercise Price of Outstanding Options, Warrants and Rights		(3) Number of Securities Remaining Available for Issuance Under Equity Compensation Plans (Excluding Securities Reflected in Column (1))
Equity compensation plans approved by security holders ^(a)		3,158,169	$	1.24		10,293,824		919,790	$	5.67		422,440
Equity compensation plans not approved by security holders		—		—		—		—		—		—
Total		3,158,169	$	1.24		10,293,824		919,790	$	5.67		422,440

Beneficial Owner	Number of Shares *Beneficially Owned ()**			Percent of Class ()**
Claudine Bruck, Ph.D.		100,000	(a)		—		(m)
Frederick O. Cope, Ph.D.		594,649	(b)		—		(m)
Adam D. Cutler		—	(c)		—		(m)
Michael M. Goldberg, M.D.		24,421,023	(d)		12.2	%
Jed A. Latkin		127,230	(e)		—		(m)
Y. Michael Rice		200,000	(f)		—		(m)
Michael S. Rosol, Ph.D.		41,667	(g)		—		(m)
S. Kathryn Rouan, Ph.D.		—	(h)		—		(m)
All directors and executive officers as a group (6 persons)		468,897	(i)(n)		—	%	(m)
Cardinal Health, Inc.		10,000,000	(j)		5.0	%
John K. Scott, Jr.		22,107,207	(k)		11.0	%
Platinum-Montaur Life Sciences, LLC		18,329,799	(l)		9.1	%

Beneficial Owner	Number of Shares Beneficially Owned			Percent of Class
Amit Bhalla		18,068	(a)		*
Alexander L. Cappello		16,477	(b)		*
Erika L. Eves		25,037	(c)		*
Michel Mikhail, Ph.D.		—	(d)		*
Michael S. Rosol, Ph.D.		58,891	(e)		*
John K. Scott, Jr.		10,242,447	(f)		31.5	%
Malcolm G. Witter		116,388	(g)		*
All directors and Named Executive Officers as a group (7 persons)		10,477,308			32.2	%

Report of Independent Registered Public Accounting Firm ~~– Marcum LLP~~	F-2

Consolidated Balance Sheets as of December 31, ~~2018~~2021 and ~~2017~~2020	~~F-3~~F-4

Consolidated Statements of Operations for the years ended December 31, ~~2018~~2021 and ~~2017~~2020	~~F-4~~

~~Consolidated Statements of Comprehensive (Loss) Income for the years ended December 31, 2018 and 2017~~	~~F-5~~F-6

Consolidated Statements of Stockholders’ ~~(Deficit)~~ Equity for the years ended December 31, ~~2018~~2021 and ~~2017~~2020	~~F-6~~F-7

Consolidated Statements of Cash Flows for the years ended December 31, ~~2018~~2021 and ~~2017~~2020	~~F-7~~F-8

Notes to the Consolidated Financial Statements	~~F-8~~F-9

Exhibit Number		Exhibit Description

3.1		Amended and Restated Certificate of Incorporation of Navidea Biopharmaceuticals, Inc., as corrected February 18, 1994, and amended June 27, 1994, July 25, 1995, June 3, 1996, March 17, 1999, May 9, 2000, June 13, 2003, July 29, 2004, June 22, 2005, November 20, 2006, December 26, 2007, April 30, 2009, July 27, 2009, August 2, 2010, January 5, 2012, June 26, 2013 and August 18, 2016) ~~(filed as~~(incorporated by reference to Exhibit 3.1 to the Company’s Annual Report on Form 10-K filed March 31, 2017 ~~and incorporated therein by reference)~~).

3.2		Certificate of Amendment to Amended and Restated Certificate of Incorporation of Navidea Biopharmaceuticals, Inc. (incorporated by reference to Exhibit 3.1 to the Company’s Current Report on Form 8-K filed April 26, 2019).

3.3		Amended and Restated By-Laws dated July 21, 1993, as amended July 18, 1995, May 30, 1996, July 26, 2007, and November 7, 2013 ~~(filed as~~(incorporated by reference to Exhibit 3.2 to the Company’s Quarterly Report on Form 10-Q filed November 12, 2013 ~~and incorporated herein by reference)~~).

3.4		Amendment to Amended and Restated By-Laws, dated April 2, 2021 (incorporated by reference to Exhibit 3.1 to the Company’s Current Report on Form 8-K filed April 5, 2021).

4.1		Certificate of Designations, Voting Powers, Preferences, Limitations, Restrictions, and Relative Rights of Series C Redeemable Convertible Preferred Stock (incorporated by reference to Exhibit 3.1 to the Company’s Current Report on Form 8-K filed May 12, 2020).

4.2		Certificate of Elimination (incorporated by reference to Exhibit 3.1 to the Company’s Current Report on Form 8-K filed September 2, 2020).

4.3		Certificate of Designations, Voting Powers, Preferences, Limitations, Restrictions, and Relative Rights of Series D Redeemable Convertible Preferred Stock (incorporated by reference to Exhibit 3.2 to the Company’s Current Report on Form 8-K filed September 2, 2020).

4.4		Certificate of Designations, Voting Powers, Preferences, Limitations, Restrictions, and Relative Rights of Series E Redeemable Convertible Preferred Stock (incorporated by reference to Exhibit 3.1 to the Company’s Current Report on Form 8-K filed March 4, 2021).

4.5		Amended and Restated Certificate of Designations, Voting Powers, Preferences, Limitations, Restrictions, and Relative Rights of Series B Cumulative Convertible Preferred Stock ~~(incorporated~~(incorporated by reference to Exhibit 4.1 to the Company’s Current Report on Form 8-K filed June 26, ~~2013)~~2013).

~~10.1~~4.6		~~Supply and Distribution~~Form of Common Stock Certificate (incorporated by reference to Exhibit 4.3 to the Company’s Registration Statement on Form S-3 filed December 31, 2019).

4.7		Description of Securities (incorporated by reference to Exhibit 4.3 to the Company’s Annual Report on Form 10-K filed March 18, 2020).

4.8		Registration Rights Agreement, dated ~~November 15, 2007, between~~December 6, 2019, among Navidea Biopharmaceuticals, Inc. and the ~~Company and Cardinal Health 414, LLC (portions of this Exhibit have been omitted pursuant to a request for confidential treatment and have been filed separately with the Commission) (incorporated~~stockholders named therein (incorporated by reference to Exhibit 10.1 to the Company’s Current Report on Form 8-K filed ~~November 21, 2007).~~

~~10.2~~		Manufacture and Supply Agreement, dated November 30, 2009, between the Company and Reliable Biopharmaceutical Corporation (portions of this Exhibit have been omitted pursuant to a request for confidential treatment and have been filed separately with the Commission) (incorporated by reference to Exhibit 10.1 to the Company’s June 30, 2010 Form 10-Q)December 11, 2019).

~~10.3~~4.9		Form of Underwriter Warrants (incorporated by reference to Exhibit 4.1 to the Company’s Current Report on Form 8-K filed June 17, 2019).

4.10		Registration Rights Agreement, dated February 13, 2020, by and between Navidea Biopharmaceuticals, Inc. and John K. Scott, Jr. (incorporated by reference to Exhibit 4.5 to the Company’s Registration Statement on Form S-3 filed August 25, 2020).

4.11		Form of Indenture (incorporated by reference to Exhibit 4.6 to the Company’s Registration Statement on Form S-3 filed February 8, 2021).

4.12		Registration Rights Agreement, dated March 2, 2021, by and between Navidea Biopharmaceuticals, Inc. and John K. Scott, Jr. (incorporated by reference to Exhibit 10.2 to the Company’s Current Report on Form 8-K filed March 4, 2021).

10.1		License Agreement, dated December 9, 2011, between AstraZeneca AB and the Company (portions of this Exhibit have been omitted pursuant to a request for confidential treatment and have been filed separately with the U.S. Securities and Exchange Commission) ~~(incorporated~~(incorporated by reference to Exhibit 10.1 to the Company’s Current Report on Form 8-K/A filed April 11, ~~2012)~~2012).

~~10.4~~Exhibit Number		~~Loan Agreement, dated July 25, 2012, between the Company and Platinum-Montaur Life Sciences LLC (incorporated by reference to~~ Exhibit ~~10.1 to the Company’s Current Report on Form 8-K filed July 31, 2012).~~Description

~~10.5~~		~~Promissory Note, dated July 25, 2012, made by Navidea Biopharmaceuticals, Inc. in favor of Platinum-Montaur Life Sciences LLC (incorporated by reference to Exhibit~~ 10.2 ~~to the Company’s Current Report on Form 8-K filed July 31, 2012).~~

~~10.6~~		Amendment to Loan Agreement, dated June 25, 2013, between Navidea Biopharmaceuticals, Inc. and Platinum-Montaur Life Sciences LLC (incorporated by reference to Exhibit 10.4 to the Company’s Current Report on Form 8-K/A filed June 28, 2013).

~~10.7~~		Amended and Restated Promissory Note, dated June 25, 2013, made by Navidea Biopharmaceuticals, Inc. in favor of Platinum-Montaur Life Sciences LLC (incorporated by reference to Exhibit 10.6 to the Company’s Current Report on Form 8-K/A filed June 28, 2013).

~~10.8~~		Series HH Warrant to purchase ~~common stock~~Common Stock of Navidea Biopharmaceuticals, Inc. issued to GE Capital Equity Investments, Inc., dated June 25, 2013 ~~(incorporated~~(incorporated by reference to Exhibit 10.2 to the Company’s Current Report on Form 8-K/A filed June 28, ~~2013)~~2013).

~~10.9~~10.3		Series HH Warrant to purchase ~~common stock~~Common Stock of Navidea Biopharmaceuticals, Inc. issued to MidCap Financial SBIC, LP, dated June 25, 2013 ~~(incorporated~~(incorporated by reference to Exhibit 10.3 to the Company’s Current Report on Form 8-K/A filed June 28, ~~2013)~~2013).

~~10.10~~10.4		Office Lease, dated August 29, 2013, by and between Navidea Biopharmaceuticals, Inc. and BRE/COH OH LLC (portions of this Exhibit have been omitted pursuant to a request for confidential treatment and have been filed separately with the U.S. Securities and Exchange Commission) ~~(incorporated~~(incorporated by reference to Exhibit 10.1 to the Company’s Current Report on Form 8-K filed September 5, ~~2013)~~2013).

~~10.11~~		Manufacturing Services Agreement, dated September 9, 2013, by and between Navidea Biopharmaceuticals, Inc. and OSO BioPharmaceuticals Manufacturing, LLC (portions of this Exhibit have been omitted pursuant to a request for confidential treatment and have been filed separately with the U.S. Securities and Exchange Commission) (incorporated by reference to Exhibit 10.1 to the Company’s Current Report on Form 8-K filed September 12, 2013).