Pyxis Oncology, Inc. 10-K

10-K UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31 , 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD FROM TO Commission File Number 001-40881 Pyxis Oncology, Inc. (Exact name of Registrant as specified in its Charter) Delaware 83-1160910 (State or other jurisdiction of incorporation or organization) (I.R.S. Employer Identification No.) 321 Harrison Avenue Boston , Massachusetts 02118 (Address of principal executive offices) (Zip Code) Registrant’s telephone number, including area code: ( 617 ) 453-3596 Securities registered pursuant to Section 12(b) of the Act: Title of each class Trading Symbol(s) Name of each exchange on which registered Common Stock, par value $0.001 per share PYXS Nasdaq Global Select Market Securities registered pursuant to Section 12(g) of the Act: None Indicate by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒ Indicate by check mark if the Registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. Yes ☐ No ☒ Indicate by check mark whether the Registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐ Indicate by check mark whether the Registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the Registrant was required to submit such files). Yes ☒ No ☐ Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act. Large accelerated filer ☐ Accelerated filer ☐ Non-accelerated filer ☒ Smaller reporting company ☒ Emerging growth company ☒ If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒ Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit re port. ☐ If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐ Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐ Indicate by check mark whether the Registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒ The aggregate market value of the Registrant’s common stock held by non-affiliates as of June 30, 2025, the last business day of the Registrant’s most recently completed second fiscal quarter, was approximately $ 64.4 million, as computed by reference to the closing price of the common stock on the Nasdaq Global Select Market on that date. Shares of the registrant's common stock held by executive officers, directors, and their affiliates have been excluded from this calculation. The determination of affiliate status is not necessarily a conclusive determination for other purposes. As of March 20, 2026, the Registra nt had 62,831,246 shares of common stock, $0.00 1 par value per share, outstanding. DOCUMENTS INCORPORATED BY REFERENCE Portions of the registrant's definitive proxy statement for its 2026 Annual Meeting of Stockholders, which the registrant intends to file pursuant to Regulation 14A with the Securities and Exchange Commission not later than 120 days after the registrant’s fiscal year ended December 31, 2025, are incorporated by reference into Part III of this Annual Report on Form 10-K. Table of Contents Page PART I Item 1. Business 5 Item 1A. Risk Factors 48 Item 1B. Unresolved Staff Comments 90 Item 1C. Cybersecurity 90 Item 2. Properties 91 Item 3. Legal Proceedings 91 Item 4. Mine Safety Disclosures 91 PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 92 Item 6. [Reserved] 92 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 93 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 102 Item 8. Financial Statements and Supplementary Data 102 Item 9. Changes in and Disagreements With Accountants on Accounting and Financial Disclosure 102 Item 9A. Controls and Procedures 102 Item 9B. Other Information 104 Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 104 PART III Item 10. Directors, Executive Officers and Corporate Governance 105 Item 11. Executive Compensation 105 Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters 105 Item 13. Certain Relationships and Related Transactions, and Director Independence 105 Item 14. Principal Accounting Fees and Services 105 PART IV Item 15. Exhibits, Financial Statement Schedules 106 Item 16. Form 10-K Summary 107 Signatures 108 i CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS This Annual Report on Form 10-K contains forward-looking statements concerning our business, operations and financial performance and condition, as well as our plans, objectives and expectations for our business, operations and financial performance and condition. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking statements. These statements involve known and unknown risks and other important factors that are in some cases beyond our control and may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Unless the context requires otherwise, references in this Annual Report on Form 10-K to “Pyxis Oncology,” the “Company,” “we,” “us,” and “our” refer to Pyxis Oncology, Inc. and its subsidiaries. In some cases, you can identify forward-looking statements by terms such as “anticipate,” “believe,” “can,” “continue,” “could,” “estimate,” “expect,” “intend,” “likely,” “may,” “might,” “objective,” “ongoing,” “plan,” “potential,” “predict,” “project,” “should,” “to be,” “will,” “would,” or the negative or plural of these words, or similar expressions or variations, although not all forward-looking statements contain these words. The forward-looking statements in this Annual Report on Form 10-K are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition and results of operations. These forward-looking statements speak only as of the date of this Annual Report on Form 10-K and are subject to a number of risks, uncertainties and assumptions described in the section titled “Risk Factors” and elsewhere in this Annual Report on Form 10-K. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Some of the key factors that could cause actual results to differ from our expectations include: • our ability to continue as a going concern; • our ability to develop and advance our current product candidate and program, and to successfully initiate and complete clinical trials; • the ability of our clinical trials to demonstrate the safety, purity and potency of our product candidate and other positive results; • the size of the market opportunity for our product candidate, including our estimates of the number of patients who suffer from the cancers we are targeting; • our manufacturing, commercialization and marketing capabilities and strategy; • the timing or likelihood of regulatory filings and approvals for our product candidate; • regulatory developments in the United States and other foreign jurisdictions; • our expectations and plans to obtain funding for our operations, including from our existing and potential future collaboration and licensing agreements; • our ability to receive milestone or royalty payments under existing or future agreements; • our expectations regarding our ability to obtain and maintain intellectual property protection for our product candidate; • our continued reliance on third parties to manufacture our product candidate for clinical studies, and to conduct clinical trials and manufacture our product candidate for such clinical trials; and • our estimates regarding expenses, future revenue, capital requirements and needs for additional financing. In addition, statements such as “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this Annual Report on Form 10-K and, although we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted a thorough inquiry into, or review of, all potentially available relevant information. Furthermore, if our forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events or otherwise. 2 SUMMARY RISK FACTORS You should consider carefully the risks described under “Risk Factors” in Part II, Item 1A of this Annual Report on Form 10-K. References to “Pyxis Oncology,” the “Company,” “we,” “us,” and “our” in this section titled “Summary Risk Factors” refer to Pyxis Oncology, Inc. and its wholly owned subsidiaries. A summary of the risks that could materially and adversely affect our business, financial condition, operating results and prospects include the following: • We are a clinical stage oncology company with a limited operating history and have incurred significant losses since our inception and anticipate that we will continue to incur losses over at least the next several years and may never achieve or maintain profitability. • We have substantial doubt about our ability to continue as a going concern and we will require substantial additional capital to finance our operations. If we are unable to raise such capital when needed, or on acceptable terms, we may not be able to continue as a going concern or we may be forced to delay, reduce or eliminate one or more of our research and product development programs or future commercialization efforts. • We are heavily dependent on the success of our lead product candidate, micvotabart pelidotin (MICVO), formerly known as PYX-201, which is in the early stages of clinical development. If our lead product candidate is not successful in clinical trials or does not receive regulatory approval or licensure or is not successfully commercialized, our business will be materially and adversely affected. • Our product candidate may fail in development or suffer delays that materially and adversely affect its commercial viability. If we or our existing or future collaborators are unable to initiate and complete clinical development of, obtain regulatory approval or licensure for or commercialize our product candidate or experience significant delays in doing so, our business will be materially harmed. • Our product candidate may cause undesirable and unforeseen side effects or have other properties impacting safety that could halt its clinical development, delay or prevent its regulatory licensure, limit its commercial potential or result in significant negative consequences. • We may face significant competition from other oncology-focused biotechnology and pharmaceutical entities, and our operating results will suffer if we fail to compete effectively. • Clinical testing and product development is a lengthy and expensive process with an uncertain outcome. We may incur unexpected costs or experience delays in completing, or ultimately be unable to complete, the clinical testing and the development and commercialization of our product candidate. • The regulatory licensure and approval processes of the FDA and other comparable foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable and, if we are unable to obtain marketing licensure or approval for our product candidate, our business will be substantially harmed. • If we fail to attract and retain qualified senior management and key scientific personnel, our business may be materially and adversely affected. • We rely on third parties to manufacture our product candidate. Any failure by a third party manufacturer to produce acceptable raw materials or product candidate for us or to obtain authorization from the FDA or comparable foreign regulatory authorities relating thereto may delay or impair our ability to initiate or complete our clinical trials, obtain regulatory licensure or approvals or commercialize approved products. • If we are unable to obtain or protect our intellectual property in and to our product candidates, we may not be able to compete effectively in our markets. • If we fail to comply with our obligations under any license, collaboration or other agreements, we may be required to pay damages and could lose intellectual property rights that are necessary for developing and protecting our product candidate or we could lose certain rights to grant sublicenses. • Licensing of intellectual property is of critical importance to our business and involves complex legal, business and scientific issues. If we breach our Pfizer license agreement or any of the other agreements under which we acquired, or will acquire, intellectual property rights covering our product candidate, we could lose the ability to continue the development and commercialization of the related product candidate(s). 3 • Actual or perceived failures to comply with applicable data protection, privacy and security laws, regulations, standards and other requirements could adversely affect our business, operations and financial condition. • Our information technology systems, or those of any of our existing or future CROs, manufacturers, other contractors, consultants, or collaborators, may be compromised, which could result in additional costs, significant liabilities, harm to our reputation and material disruption of our operations. 4 PAR T I Item 1. Business. Overview Pyxis Oncology is a clinical-stage oncology company advancing a development strategy focused on addressing unmet medical needs in patients with solid tumors with an immediate focus on head and neck squamous cell carcinoma (HNSCC). Our lead product candidate, micvotabart pelidotin (MICVO, formerly PYX-201), is an investigational novel antibody-drug conjugate (ADC) that uniquely targets the splice variant of fibronectin, extradomain-B of fibronectin (EDB+FN), a non-cellular structural component of the extracellular matrix (ECM) in the tumor microenvironment (TME). EDB+FN is an isoform of fibronectin present in tumors that is negligibly expressed in normal adult tissues and facilitates cancer progression by playing multiple roles including promoting cell proliferation, adhesion, and migration, activating the integrin signaling pathway, stimulating angiogenesis and vascular remodeling, driving epithelial-mesenchymal transition (EMT), and establishing the pre-metastatic niche. We believe EDB+FN is a compelling target for cancer therapeutics as the physiological expression of EDB+FN is very low in healthy adult tissues, yet it is found to be highly expressed in a variety of solid tumors. Our ADC, MICVO, consists of a fully human IgG1 monoclonal antibody that is site-specifically conjugated to a cleavable linker with an optimized auristatin (Aur0101) microtubule inhibitor payload. Unlike conventional ADCs which bind to an antigen on the surface of a cancer cell, MICVO is designed to bind to EDB+FN in the tumor ECM, where extracellular proteases under acidic conditions cleave the linker to release the Aur0101 payload. The payload diffuses through the membrane of cancer cells to kill them directly, which is the first component of MICVO’s three-pronged mechanism of action (MOA). The dying cancer cells release the payload which diffuses into nearby cancer cells and kills them via the bystander effect, representing the second component of MICVO’s MOA. The dying cancer cells also release neoantigens which trigger immunogenic cell death (ICD), the final component of its MOA. Together with its purpose-built design and postulated three-pronged MOA, MICVO has the potential for improved stability and anti-tumor activity compared to conventional ADCs. MICVO is currently being studied as monotherapy in recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) and in combination with KEYTRUDA® (pembrolizumab) in 1L/2L+ R/M HNSCC and other solid tumors. MICVO Monotherapy PYX-201-101 Phase 1 (Part 1) Monotherapy Dose Escalation Study As part of our Phase 1 monotherapy study, referred to as PYX-201-101, we conducted a dose escalation study to evaluate MICVO monotherapy in patients with advanced solid tumors known to express EDB+FN. In November 2024, we reported positive preliminary results from the dose escalation study, which included a total of 80 patients dosed across nine solid tumor types at doses ranging from 0.3 mg/kg to 8 mg/kg, with a data cut-off of October 4, 2024. Of the nine solid tumor types included in the study, the strongest tumor regression response was observed in R/M HNSCC. Among the six efficacy evaluable heavily pre-treated patients with R/M HNSCC, the confirmed objective response rate (ORR) was 50% per RECIST v1.1 at the therapeutically active dose response range of 3.6 mg/kg – 5.4 mg/kg administered intravenously every three weeks (IV Q3W), including one confirmed complete response (CR) and two confirmed partial responses (PRs), with a disease control rate (DCR) of 100%. Based on observations from the dose-escalation study, 5.4 mg/kg IV Q3W presented an optimal benefit-risk profile within the efficacious dose range and was selected for dose expansion. Subsequent translational data indicated reduction in ctDNA TF after treatment with MICVO, particularly at the 5.4 mg/kg dose, supported a positive molecular response to MICVO, providing further validation of the dose selection strategy for dose expansion. PYX-201-101 Phase 1 (Part 2) Monotherapy Dose Expansion in R/M HNSCC In January 2025, we initiated the dose expansion portion (Part 2) of the Phase 1 PYX-201-101 monotherapy study to further evaluate MICVO as a monotherapy at a dose of 5.4 mg/kg IV Q3W and to assess preliminary efficacy in R/M HNSCC. The Part 2 dose-expansion phase includes the following two cohorts: • Arm 1: MICVO monotherapy for second line (2L) and third line (3L) R/M HNSCC patients who have received prior platinum-based chemotherapy and prior PD-(L)1 inhibitor therapy; and • Arm 2: MICVO monotherapy for 2L and 3L R/M HNSCC patients who have received prior epidermal growth factor receptor (EGFR) directed therapy and prior PD-(L)1 inhibitor therapy. 5 In December 2025, we reported positive preliminary data from our ongoing Phase 1 monotherapy study evaluating MICVO in patients with 2L+ R/M HNSCC, based on a data cut-off date of November 3, 2025, which included all R/M HNSCC patients dosed at 5.4 mg/kg total body weight (TBW) in Part 1 and in Part 2. As of the data cut-off, 18 R/M HNSCC patients had been treated and 13 patients were efficacy evaluable. All treated patients had received prior systemic therapy, with a median of three prior lines of therapy. All treated patients had received prior platinum-based and checkpoint inhibitor therapies while 67% of treated patients had received prior taxanes and 50% of treated patients had received prior EGFR-targeted therapies, specifically cetuximab. Among the 13 efficacy evaluable patients, the confirmed ORR was 46% (6/13, one patient confirmed response after November 3, 2025 data cut-off) per RECIST v1.1, including one confirmed complete response. Confirmed responses were observed in both dose-expansion cohorts, including patients previously treated with platinum-based therapy and anti-PD(L)1 therapy (Arm 1) and patients previously treated with an EGFR inhibitor and/or anti-PD(L)1 therapy (Arm 2), and were observed in patients regardless of HPV status. The preliminary data also showed a DCR of 92%, with 12 of 13 efficacy evaluable patients demonstrating significant tumor regression or tumor control. Preliminary data reported in December 2025 indicated that MICVO was generally well tolerated. No Grade 4 ADC payload treatment-related adverse events (TRAEs) of interest were observed, and no Grade 5 events occurred. TRAEs were reported in 89% (16/18) of patients, with Grade ≥3 TRAEs reported in 56% (10/18) of patients. TRAEs leading to treatment discontinuation occurred in 28% (5/18) of patients. We observed a higher discontinuation rate and incidence of Grade ≥3 TRAEs in high body weight patients (defined as at least 10% above adjusted ideal body weight, or AIBW). In the preliminary dataset, all patients (5/5) who experienced TRAEs leading to treatment discontinuation had high body weight. Several approved ADCs have demonstrated comparable associations among patient body weight, systematic drug exposure, and tolerability profiles. Many of these ADCs, such as Padcev, Adcetris, and Elahere, have addressed such observations through dosing modifications that resulted in an improved tolerability profile while sustaining efficacy, including through capping the maximum allowable dose or employing AIBW dosing. We are actively evaluating both of these approaches to optimize MICVO’s benefit-risk profile. MICVO Combination Therapy In November 2024, we announced a Clinical Trial Collaboration and Supply Agreement with Merck & Co, Inc. or Merck (known as MSD outside of the United States and Canada), for a Pyxis Oncology-sponsored study of MICVO in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab). In January 2025, we initiated the Phase 1/2 combination study with KEYTRUDA®, PYX-201-102, and are actively enrolling and dosing patients in this study. PYX-201-102 is a Phase 1/2 open label, global, multicenter dose escalation and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of MICVO in combination with pembrolizumab in patients with advanced solid tumors. Patients with histologically or cytologically confirmed advanced solid tumors, including 1L R/M HNSCC, 2L+ R/M HNSCC, cervical cancer, gastric cancer, HR+/HER2- breast cancer, and locally advanced or metastatic triple-negative breast cancer (TNBC), are eligible to enroll. PYX-201-102 Phase 1/2 Preliminary Combination Data in R/M HNSCC In December 2025, we reported positive preliminary data from this study, evaluating MICVO at 3.6 mg/kg and 4.4 mg/kg IV Q3W, each administered in combination with a fixed 200 mg dose of pembrolizumab Q3W, in patients with 1L/2L+ R/M HNSCC. As of the data cut-off date of November 3, 2025, seven patients had been treated, including four patients at 3.6 mg/kg and three patients at 4.4 mg/kg of MICVO, each in combination with pembrolizumab. All treated patients had received prior systemic therapy, including four patients with 1L R/M HNSCC (median of one prior systemic therapy administered in the neoadjuvant or adjuvant setting) and three patients with 2L+ R/M HNSCC (median of three prior lines of therapy, some of which were administered prior to the R/M setting). Among the seven efficacy-evaluable patients, the confirmed ORR was 71% (5/7, one patient confirmed response after November 3, 2025 data cut-off) and the DCR was 100% (7/7), with all seven patients demonstrating meaningful tumor regression. Responses were observed across a range of PD-L1 combined positive scores (CPS), from CPS≥1 to CPS>20, and included responses in patients who had previously received checkpoint inhibitor treatment and had experienced disease progression while receiving checkpoint inhibitor treatment. Preliminary safety data indicated that MICVO in combination with pembrolizumab was generally well tolerated, with no Grade 3 or Grade 4 ADC payload TRAEs of interest and no Grade 5 events reported. TRAEs were reported in 86% (6/7) of patients. No TRAEs led to treatment discontinuation, and, as of the data cut-off date, no overlapping toxicities between MICVO and pembrolizumab (KEYTRUDA®) had been observed. We believe the totality of our preliminary data supports continued clinical development of both MICVO monotherapy expansion and combination therapy trials. 6 Our Clinical Pipeline The following table summarizes our clinical pipeline: MICVO Monotherapy Pipeline The dose expansion phase of our PYX-201-101 monotherapy study is ongoing with the objective of further evaluating the preliminary safety, efficacy and durability signals observed with MICVO in R/M HNSCC at the 5.4mg/kg dose. We completed target enrollment of approximately 40 patients in the Phase 1 monotherapy dose expansion study of MICVO in 2L+ R/M HNSCC in the first quarter of 2026 and are actively treating patients in two monotherapy R/M HNSCC cohorts at the 5.4 mg/kg IV Q3W dose. The dose expansion phase includes the following R/M HNSCC cohorts across sites in the United States (US), European Union (EU) and other countries: • MICVO monotherapy for 2L and 3L R/M HNSCC patients who have received prior platinum-based chemotherapy and prior PD-(L)1 inhibitor therapy. We expect to enroll approximately 20 patients in this expansion cohort at the 5.4 mg/kg IV Q3W dose and anticipate reporting updated clinical data from this cohort in mid-2026; and • MICVO monotherapy for 2L and 3L R/M HNSCC patients who have received prior epidermal growth factor receptor (EGFR) directed therapy and prior PD-(L)1 inhibitor therapy. We expect to enroll approximately 20 patients in this expansion cohort at the 5.4 mg/kg IV Q3W dose and anticipate reporting updated clinical data from this cohort in mid-2026. MICVO Phase 1 monotherapy data in 2L+ R/M HNSCC expected in mid-year 2026 will include patients dosed at 5.4 mg/kg IV Q3W with a dose cap for patients with higher body weight, as well as patients previously dosed at 5.4 mg/kg IV Q3W based on total body weight. The results are expected to include detailed analyses of the effect of the modified weight-based dosing strategy on safety and efficacy. AIBW dosing, which has demonstrated improved tolerability without apparent loss of activity in clinical studies of other antibody-drug conjugates, is being implemented in ongoing clinical studies as well. During the fourth quarter of 2025, we obtained feedback and alignment from the U.S. Food and Drug Administration (FDA) regarding the clinical trial design for a planned pivotal monotherapy study in 2L+ R/M HNSCC. MICVO Combination Therapy Pipeline Our Phase 1/2 combination study with KEYTRUDA® (PYX-201-102) is ongoing and we are conducting the dose escalation phase of PYX-201-102 across multiple tumor types with the objective of identifying the Recommended Phase 2 Dose (RP2D) of MICVO in combination with pembrolizumab. We are currently enrolling and dosing patients across several dose levels between 3.6 mg/kg and 5.4 mg/kg of MICVO, in combination with pembrolizumab at the fixed dose of 200 mg IV Q3W, in order to accurately characterize the RP2D for MICVO in combination with pembrolizumab, subject to ongoing safety review, enrollment progress, and clinical data evaluation. We expect to report updated data from the PYX-201-102 study in patients with 1L/2L+ R/M HNSCC in the second half of 2026. Our Team Pyxis Oncology was founded in 2018 and began operations in 2019 with a mission to address difficult-to-treat cancers. We have assembled a multidisciplinary team with experience across core oncology research and development functions and corporate and administrative operations. Collectively, our team brings experience spanning early- through late-stage development and, in certain cases, commercialization, across biotechnology and pharmaceutical organizations. 7 Our Strategy Our goal is to improve the lives of patients with difficult-to-treat cancers. Key elements of our strategy include: • Building a leading ADC oncology company. We believe our team, with its deep oncology knowledge, functional biology expertise, ADC modality technical know-how and biologics development capabilities, positions us to build a leading ADC-focused oncology company. • Successfully developing our lead product candidate, MICVO, to address significant unmet need in R/M HNSCC. We are prioritizing development of our lead product candidate, MICVO, for R/M HNSCC, where we believe there is significant unmet need for durable therapeutic options. HNSCC is among the most common cancers, and it has been estimated that approximately one million new cases could occur worldwide annually by 2030. Our prioritization reflects, among other factors, the unmet need in this patient population and the preliminary activity observed to date in the PYX‑201‑101 monotherapy and PYX-201-102 combination program. • Selectively forging alliances to provide strategic or financial support to our lead MICVO program. We intend to seek strategic collaborations to facilitate the capital efficient development of our pipeline. We believe various potential alliance structures including collaborations, licenses and future agreements could potentially provide significant funding to advance our pipeline and could allow us to benefit from the additional resources, development and commercialization expertise of our collaborators. • Maximize value from our intellectual property and technology platforms. We continue to engage in discussions with potential partners regarding opportunities to monetize elements of our intellectual property portfolio, including certain programs that are not currently being actively resourced. We also seek to maximize the value of our biologics technology platforms, including our Flexible Antibody Conjugation Technology (FACT) platform for ADC development and our APXiMAB platform for antibody discovery and development. Unmet Need in Head and Neck Cancer and Treatment Paradigm Head and Neck Cancer (HNC) is the seventh most common cancer in the world (Source: NIH), with 940,000 new cases and 480,000 deaths from HNC per 2022 GLOBOCAN estimates. GLOBOCAN is a cancer surveillance branch of the World Health Organization’s International Agency for Research on Cancer (Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC12507627/). Squamous Cell Carcinoma presents as the most common HNC subtype and is derived from the mucosal lining of the oral cavity, oropharynx, hypopharynx and larynx. It is estimated that by 2030 there will be approximately one million new cases of HNSCC worldwide annually per 2022 GLOBOCAN estimates. HNC accounts for approximately 4.5% of cancer diagnoses and deaths globally with over 90% of cases presenting with squamous cell origin. HNSCC commonly originates in the mouth and throat, from the mucosa of the oral cavity, oropharynx, hypopharynx and larynx. There are approximately 60,000 cases of HNSCC each year in the U.S. with a 13% 5-year survival rate in the R/M (Stage IVC) setting. 15% of HNSCC patients are diagnosed with de novo metastatic disease and almost 50% of locally advanced cases will suffer a recurrence post initial treatment and/or become metastatic. There are approximately 31,000 cases of R/M HNSCC each year in the U.S. with ~67% (~21,000) of patients progressing from 1L to 2L and facing a sharp decline in survival. The median Overall Survival (OS) for patients with 1L R/M HNSCC ranges from 9 months (HPV unrelated) to about 14 months (HPV+). The overall incidence of HNSCC is expected to rise with a predicted 30% increase annually by 2030. The increase has been associated with multiple factors, including but not limited to tobacco use, alcohol consumption, a rise in HPV infections and other environmental catalysts. Approximately 80% of patients in the U.S. with R/M HNSCC are HPV unrelated. Globally, these numbers vary with higher rates of HPV+ cancers in countries such as New Zealand and parts of Northern Europe. The vast majority of HPV+ HNSCC cases are detected in the oropharyngeal cavity versus other locations (oral cavity, pharynx, larynx etc.) with approximately 5,500 cases of virally driven tumors diagnosed in the U.S. each year. Furthermore, HPV+ HNSCC is also on the rise in the U.S. with a greater number of oropharyngeal cancer cases diagnosed every year, suggesting potential shifts in how patients will be diagnosed and treated based on possible HPV segmentation. 8 Current Treatment Paradigm of R/M HNSCC The standard of care (SOC) first line therapy for R/M HNSCC globally is determined by the Combined Positive Score (CPS) which corresponds to the number of PD-L1 positive cells in relation to the total number of viable tumor cells. Patients with high CPS scores tend to respond better to PD-(L)1 checkpoint inhibitors, as observed across multiple tumor types. In R/M HNSCC, pembrolizumab monotherapy (was previously approved for CPS≥20) is recommended for patients with a CPS > 1 post label expansion based on KEYNOTE-048 (KN_048) (~26,000 addressable patients). However, addition of platinum-based chemotherapy is strongly considered in these patients if they are symptomatic or present with aggressive disease. Pembrolizumab combined with platinum and 5-fluorouracil is recommended for patients with any PD-L1 status of CPS≥1 essentially providing a monotherapy or combo option to all patients considered PD-L1+ with different treatment options adopted by region worldwide. While approved, the chemo combination is not always reimbursed by the health authorities in certain parts of Europe but is the most commonly used regimen in the U.S. The addition of chemotherapy to pembrolizumab increases the response rate; however, it also significantly reduces the duration of response while increasing toxicity and leads to roughly equivalent median overall survival (OS) with both treatments. For patients with a CPS<1 and no PD-L1 expression, the typical standard of care is the EXTREME regimen (not in the U.S.), a combination of cetuximab and chemotherapy, which has low response rates and survival (10 months), as well as a difficult tolerability profile. The EXTREME regimen is more commonly used in Europe and other ex-US countries with less than 5% usage in the U.S. Patients with CPS<1 in the US receive a chemotherapy combination consisting of platinum (cisplatin or carboplatin) with 5-fluorouracil to lower toxicity associated with addition of cetuximab. While the 1L R/M HNSCC treatment paradigm is well defined, globally, limited options are available for patients that fail therapy and move into 2L and beyond. If patients are treated with immuno-oncology (IO) in 1L, they are not eligible for re-treatment and the only therapy approved is chemotherapy. Cetuximab (with or without chemo) does not have an approved FDA or EMA label post IO but is recommended by certain clinical practice and regulatory guidelines set forth by some countries including the NCCN in the US. Patients that are platinum refractory or not treated with IO in 1L are eligible for pembrolizumab or nivolumab monotherapy in 2L but progression free survival (mPFS) benefit remains modest at 2-3 months, highlighting need for a more efficacious option in these patients. The Phase 3 KN-048 trial conducted by Merck investigated pembrolizumab as a monotherapy or in combination with chemotherapy, compared to cetuximab with chemotherapy in first line R/M HNSCC. The pembrolizumab monotherapy and pembrolizumab and chemotherapy combination response rates of 19% and 36%, respectively, were comparable to the 36% ORR for cetuximab and chemotherapy combination in patients with CPS > 1. In these patients, pembrolizumab monotherapy and in combination with chemotherapy led to median OS of 12.3 and 13.0 months, respectively, compared to 10.7 months in the active control arm. While this represents a step forward, there remains significant unmet need in R/M HNSCC for more efficacious therapies that can extend survival, especially for chemotherapy-free alternatives with superior tolerability and also differentiated treatment modalities that can serve the emerging unmet need populations as the treatment paradigms may evolve. Patients that are not eligible for 1L pembrolizumab (CPS<1) represent ~3500 patients and lack efficacious treatment options that offer durable survival and quality of life. Furthermore, pembrolizumab was also recently approved in the adjuvant and neo-adjuvant setting allowing subsets of localize/locally advanced patients to benefit from IO in the peri-operative setting. Use of IO in earlier disease may impact use in the R/M setting which may result in additional shifts to the R/M HNSCC landscape. HPV status also does not play a role in patient segmentation and treatment choices based on approved SOC but a shift may occur as emerging therapies may prove to be superior in one patient segment versus another. This could open up newer patient groups with unmet needs that may not be fulfilled by current or emerging therapies, particularly in the 2L+ setting given that HPV+ patients have historically shown poor response rates to EGFR therapies. Emerging Treatment Landscape of R/M HNSCC Currently, several companies are innovating next-generation EGFR assets and bi-specific antibodies to address the needs of HNSCC patients, including Genmab A/S (Genmab) via its acquisition of Merus N.V (Merus), Bicara Therapeutics Inc. (Bicara) and Johnson & Johnson (JNJ). Genmab, Bicara and JNJ have ongoing clinical trials evaluating antibodies targeting EGFR - petosemtamab, ficerafusp alfa (BCA101), and RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj), respectively, as a monotherapy or as a combination therapy with pembrolizumab for the treatment of R/M HNSCC solid tumors, with a focus on combination therapy for 1L. All assets have been granted breakthrough designation (BTD) by the U.S. Food and Drug Administration (FDA) in R/M HNSCC. Genmab has two Phase 3 clinical trials ongoing, 1L treatment of R/M PD-L1+ (CPS≥1) HNSCC in combination with pembrolizumab and 2L/3L R/M HNSCC monotherapy. Bicara has ongoing trials for the treatment of 1L R/M HNSCC, including a Phase 2/3 combination trial with pembrolizumab in HPV unrelated patients only (1L, CPS>1). JNJ also has ongoing trials for the treatment of 1L R/M HNSCC in HPV unrelated patients only. Aside from these next-generation EGFR assets, Corbus Pharmaceuticals has ongoing clinical trials evaluating a Nectin-4 targeting ADC, CRB-701, for the treatment of 2L+ R/M HNSCC with monotherapy and 1L R/M HNSCC in combination with pembrolizumab. Additionally, other agents like Nanobiotix’s radioenhancer, NBTRX3, are in clinical development and may be used earlier in the treatment sequence such as in localized or locally advanced settings. Other modalities including but not limited to T cell engagers may segment market further into HPV+ specific treatments along with other emerging segmentations that may trigger a change in clinical practice. These evolving shifts naturally result in the development of new patient populations (particularly in the R/M setting) that are left with limited treatments and generate a new unmet need. For example, the use of IO in the surgical setting may limit its use in the 1L segments while the use of next-generation of EGFRi in 1L may create a growing need for therapies post IO and EGFRi. Emerging therapies may be potentially limited to specific patient segments such as HPV+ or HPV unrelated patients or CPS>1 only. Furthermore, patients that fail existing and emerging therapies are more likely to have poor performance status, which will necessitate that the next tranche of treatment options be tolerable so patients can stay longer on the treatment and derive a survival benefit. 9 Our Solution: MICVO, a Novel ADC MICVO is an investigational novel ADC that is designed to uniquely target the splice variant of fibronectin, EDB+FN, a non-cellular structural component of the ECM in the TME. The TME is a complex ecosystem consisting of cancer cells, stroma, immune cells, blood vessels and secreted factors like cytokines. The tumor stroma consists of cancer-associated fibroblasts (CAFs) and ECM which is interspersed throughout the TME. The tumor ECM consists of many proteins like fibronectin and some, not all, fibronectin proteins in the tumor ECM are EDB+FN. Fibronectin is a key component of healthy ECM and is involved in the regulation of cell adhesion, migration, differentiation and wound healing. In tumors, fibronectin strands within the ECM, along with other proteins and polysaccharides, form a complex scaffold that gives the tumor shape and play critical roles in the tumor ECM remodeling process to promote progression and metastasis. EDB+FN is an isoform of fibronectin present in tumors and negligibly expressed in normal adult tissues resulting from alternative splicing, a process that occurs when ribonucleic acid (RNA) is re-arranged to produce multiple variants of the same protein. EDB+FN facilitates cancer progression by playing multiple roles including promoting cell proliferation, adhesion, and migration, activating the integrin signaling pathway, stimulating angiogenesis and vascular remodeling, driving epithelial-mesenchymal transition (EMT), and establishing the pre-metastatic niche. The localization of EDB+FN in the tumor ECM is illustrated in Figure 1 below. Figure 1 The tumor ECM can form an effective barrier to entry of therapeutic agents such as some chemotherapies. Although the tumor ECM plays a significant role in the initiation, growth, survival, invasion and drug resistance of solid tumors, few therapeutics specifically target tumor-specific ECM proteins. Our ADC, MICVO, consists of a fully human IgG1 monoclonal antibody that is site-specifically conjugated to a cleavable linker with an optimized auristatin (Aur0101) microtubule polymerization inhibitor payload. MICVO was developed using the Flexible Antibody Conjugation Technology (FACT) Platform, developed by Pfizer, to produce an ADC designed to be highly stable with a predictable and homogenous drug-to-antibody ratio (DAR) of four. The complementarity determining regions of the EDB+FN antibody used in MICVO, which is the part of the antibody responsible for binding to EDB+FN, is well characterized and has been tested clinically in the form of a radiolabel-conjugated antibody for tumor imaging demonstrating a high degree of tumor-directed specificity. Unlike conventional ADCs which bind to an antigen on the surface of a cancer cell, MICVO is designed to bind to EDB+FN in the tumor ECM, where extracellular proteases under acidic conditions cleave the linker to release the Aur0101 payload. The payload diffuses through the membrane of cancer cells to kill them directly, which is the first component of MICVO’s three-pronged MOA. The dying cancer cells release the payload which diffuses into nearby cancer cells and kills them via the bystander effect, representing the second component of MICVO’s MOA. The dying cancer cells also release neoantigens which trigger immunogenic cell death (ICD), the final component of its MOA. Together with its purpose-built design and postulated three pronged MOA, MICVO has the potential for improved stability and anti-tumor activity compared to conventional ADCs. The MOA for MICVO is illustrated in Figure 2 below. 10 Figure 2 EDB+FN is highly expressed in a variety of cancers, including, but not limited to, cancers of the head and neck, breast, lung, ovary, pancreas, and thyroid as compared to a matched set of normal tissues. EDB+FN expression is detectable as early as stage 1 of cancer progression and increases in more advanced stages. Furthermore, EDB+FN expression is maintained in distant metastasis in human cancer. The broad expression of EDB+FN protein in the ECM of the tumor of many cancer types as compared to negligible expression in normal adult tissues is shown in Figure 3 below. 11 Figure 3 We believe EDB+FN is a compelling target for cancer therapeutics as the physiological expression of EDB+FN is very low in healthy adult tissues, yet it is found to be highly expressed in a variety of solid tumors. By targeting EDB+FN in the tumor ECM, our goal is to deliver a cytotoxic payload directly to the tumor and be released extracellularly within the acidic tumor ECM to permeate the tumor, diffuse into and kill cancer cells and stimulate an immune response to further enhance cancer cell killing, all without requiring the ADC itself to reach the cancer cell and be internalized. Additionally, MICVO may also remodel the TME to destabilize the barrier that protects, feeds and provides structure to the tumor while sparing healthy cells. MICVO is designed to exhibit anti-tumor activity through three distinct modes of action: • Direct cancer cell killing activity : MICVO targets EDB+FN within the tumor ECM where active extracellular proteases in an acidic microenvironment cleave the linker and release the cytotoxic chemotherapy payload which then diffuses into and kills the cancer cells. • Additional bystander killing : Dying cancers cells release the free payload which then diffuses into and kills nearby cancer cells via the bystander effect. • Immunogenic cell death : Lastly, dying cancer cells release neoantigens which stimulate immune cell activation and induce immunogenic cell death. Preclinical Data In April 2025, we presented preclinical data at the 2025 American Association for Cancer Research (AACR) Annual Meeting in Chicago, Illinois. We observed broad anti-tumor activity for MICVO across ten solid tumor indications in PDX models. Tumor responsiveness to the optimized cytotoxic Auristatin0101 payload did not correlate with EDB+FN target expression but did associate with gene expression signatures indicative of proteolytic activity for MICVO linker cleavage. The preclinical data are summarized below and shown in Figure 4: • 45% of models demonstrated strong to very strong tumor growth inhibition (TGI%) activity (70%<TGI<90% or TGI>90% respectively), with only 25% of models showing no response (TGI<25%). • PDX models with very strong activity (TGI>90%) were found across nine out of ten solid tumor indications. • Complete responses to MICVO (tumor volume reached 0mm3 for at least two consecutive measurements) were found across several tumor indications, consistent with previous analysis. • MICVO was observed to be well-tolerated (3mg/kg, Q4Dx4). 12 Figure 4 We also performed differential gene expression analysis, which enabled us to identify gene signatures linked to anti-tumor activity consistent with our extracellular linker cleavage ADC hypothesis. We observed that enzyme and tumor stroma gene signatures were the gene sets with the greatest number of differentially expressed genes. Further, the preclinical data showed upregulation of certain proteases that may contribute to increased linker cleavage and subsequent increased anti-tumor activity for MICVO, supporting our extracellular linker cleavage hypothesis. We also conducted preclinical studies combining a mouse analog of MICVO with anti-PD-1 therapy in a syngeneic mouse model of triple negative breast cancer (EMT6) known to be sensitive to PD-1 blockade. The combination of a mouse analog of MICVO with anti-PD-1 therapy inhibited EMT6 tumor growth and improved survival compared to either treatment alone, suggesting potential benefit for combination therapy to deepen anti-tumor responses in solid tumors. The preclinical studies combining a mouse analog of MICVO with anti-PD-1 therapy are summarized below: • Monotherapy of mouse analog of MICVO inhibited dose-dependent tumor outgrowth of EDB+FN expressing EMT6 tumors and was well-tolerated at 6 mg/kg. • The mouse analog of MICVO boosted the immune response by activating dendritic cells and increasing CD45+ immune cell infiltration, including PD-1+ T cells, into tumors, transforming EMT6 tumors into immune-infiltrated, "hot" tumors. • Significant TGI observed with mouse analog of MICVO (TGI=94%) and anti-PD-1 therapy (TGI=54%) as monotherapies. • The combination of the mouse analog of MICVO and anti-PD-1 therapy resulted in TGI of 91% and complete response was seen in 9/15 animals – greater tumor regression and clearance than either treatment alone. • Mouse analog of MICVO in combination with anti-PD-1 therapy induced lasting immunological memory, enhancing tumor clearance and protecting against tumor recurrence in rechallenged mice. The preclinical data indicated MICVO alone may be eliciting immune responses in immune excluded/immunologically cold tumors, as observed with the infiltration of T cells into the tumor, representing potential for MICVO to drive immunogenic cell death (ICD). Together, these preclinical data further support the three-pronged mechanism of action of MICVO driving anti-tumor activity via direct tumor killing, bystander effect and ICD. Recent Translational Data In October 2025, we presented translational data at the European Society of Medical Oncology (ESMO) Congress 2025 in Berlin, Germany and at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, Massachusetts. Data presented build on preclinical data previously presented in April 2025 at AACR Annual Meeting in Chicago. The poster presentations at the ESMO and AACR-NCI-EORTC meetings provide deeper insights into the pharmacodynamic responses of tumors to MICVO as well as MICVO’s unique mechanism of action and its potential to exert anti-tumor activity through three mechanisms: direct cancer cell killing, bystander killing and ICD. These translational findings highlight MICVO’s effects on TME remodeling, immune activation and tumor infiltration, further reinforcing the potential benefit of MICVO as both monotherapy and in combination with anti-PD-1 therapy. 13 Additional data supporting MICVO’s MOA indicate this ADC binds very specifically to EDB+FN in the TME, an important trait for the non-cellular tumor ECM targeting MOA, locally delivering the ADC close to the malignant cells for cancer cell killing after extracellular linker cleavage. Data also indicate MICVO binds strongly to EDB+FN, which enables the ADC to stay anchored in the TME longer allowing more time for extracellular linker cleavage by proteases. In vitro data presented indicate MICVO’s linker can be cleaved extracellularly via specific cathepsins and pH conditions that exist in the TME, which allows the payload to be released extracellularly to then diffuse into cancer cells. Multiple posters supported MICVO’s ability to induce ICD and a mouse analog of MICVO (maMICVO) stimulated an immune response in tumors from a syngeneic triple negative breast cancer model (4T1) that had been refractory to anti-PD-1. Synergistic antitumor activity was observed in this anti-PD-1 refractory model when maMICVO was combined with anti-PD-1. The preclinical studies combining maMICVO with anti-PD-1 therapy in the 4T1 model are summarized below: • Mouse anti-PD-1 alone had no effect on tumor growth, consistent with published studies. • maMICVO alone inhibited 4T1 tumor growth. • Synergistic anti-tumor activity was observed when both treatments were combined. • maMICVO induced the infiltration of progenitor exhausted T cells (Tpex) into 4T1 tumors. Observations of translational data from clinical samples include changes in circulating tumor DNA (ctDNA) tumor fraction (TF) after treatment with MICVO to the vast majority of 37 clinical samples tested from the monotherapy dose escalation study. Notably, reduction in ctDNA TF after treatment with MICVO, particularly in HNSCC and at the 5.4 mg/kg dose, supported a positive molecular response to MICVO and strengthened rationale for continued development of this tumor type and dose in the monotherapy dose expansion study. Analysis of baseline tumor tissues from participants in the monotherapy dose escalation trial showed EDB+FN protein level did not directly correlate with sensitivity to MICVO, which was consistent the preclinical PDX study. However, features observed in nonclinical samples of the stromal architecture detected using digital pathology may correlate with sensitivity to MICVO, a finding that may be unique compared to tumor cell surface targeting ADCs, due to MICVO’s targeting of a non-cellular structural component of the tumor ECM. Preliminary analysis of clinical tumor biopsy samples revealed that MICVO remodeled the TME as well as induced an immune response, consistent with observations in tumors from the preclinical syngeneic EMT6 mouse model. The findings observed from the clinical biopsy studies are summarized below: • Histological evaluation of a limited set of matched pair biopsies from participants treated with MICVO demonstrated pharmacodynamic effects on both cancer cells and stromal remodeling across clinical responses, reflective of the mechanism of action of this novel non-cellular targeting ADC. • MICVO reduced cellular density in both tumor epithelium and stroma compartments after two cycles of treatment but did not deplete EDB+FN expression in the cancer stroma, maintaining target expression. • Pharmacodynamic effects of MICVO on stroma included increased FN fluorescence intensity and changes in stromal cell composition, reflective of stromal remodeling. • MICVO increased the density of non-immunosuppressive T-cells in the tumor parenchyma, with increased infiltration associated with better clinical response (see example in Figure 5 below). • Greater MICVO-induced T-cell infiltration was correlated with longer time on study. • MICVO increased immune gene expression signatures within tumors. Figure 5 14 Figure 5 shows a representative image of multiplex immunofluorescence CD3 density maps on a matched baseline and on-treatment tumor biopsy pair from a MICVO monotherapy trial participant with ovarian cancer showing increased density of CD3 cells in the tumor after treatment with MICVO. Taken together, we believe that MICVO may generate a multi-pronged attack on difficult-to-treat cancers by specifically targeting the ADC to the tumor ECM where the extracellularly released cytotoxic payload can permeate the tumor and directly kill cancer cells, impact ECM remodeling and mobilize an anti-tumor immune response (as illustrated in Figure 2 above). Further, we believe that the non-cellular approach targeting the tumor ECM may potentially avoid the primary cause of drug resistance identified for therapeutics targeting cell surface receptors. Downregulated expression of therapeutic targets on cancer cells such as HER2 and EGFR has been demonstrated to be a resistance mechanism for therapies targeting these cell-surface proteins. Given the non-cellular expression profile of EDB+FN, we believe this resistance mechanism does not apply to MICVO and is supported by the observed maintenance of target expression in on-treatment biopsies evaluated thus far. Upcoming Translational Data In March 2026, we announced the publication of an abstract at the 2026 AACR Annual Meeting describing the anti-tumor activity of a murine analog of MICVO (maMICVO) in the poorly immunogenic and immunotherapy-refractory mouse oral carcinoma 2 (MOC2) syngeneic HNSCC model. The abstract also reported that image analysis suggested modulation of the tumor immune microenvironment following maMICVO treatment, which provided a scientific rationale for evaluating maMICVO in combination with anti-PD-1 in this refractory model. We expect to present this preclinical data at the AACR Annual Meeting in San Diego, CA, in April 2026. Clinical Development of MICVO PYX-201-101 Monotherapy Phase 1 Trial of MICVO We are conducting a multi-part Phase 1 trial of MICVO, referred to as PYX-201-101, which initiated patient dosing in March 2023. The study is evaluating MICVO as a monotherapy in patients with advanced solid tumors known to express EDB+FN. PYX-201-101 (Part 1) is an open-label, multicenter, dose-escalation Phase 1 trial designed to assess the safety and tolerability of MICVO, characterize its PK and PD profile, evaluate preliminary anti-tumor activity, and identify recommended dose levels for further clinical development. Eligible patients include those with relapsed or refractory advanced solid tumors, including patients with R/M HNSCC, hepatocellular carcinoma (HCC), hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer, locally advanced or metastatic non-small cell lung cancer (NSCLC), ovarian cancer, pancreatic ductal adenocarcinoma (PDAC), renal cell carcinoma (RCC), sarcoma, thyroid cancer, and TNBC. Information regarding this clinical trial is available at ClinicalTrials.gov under identifier NCT05720117. PYX-201 -101 Phase 1 Dose Escalation (Part 1) Preliminary Clinical Data In November 2024, we reported positive preliminary data from Part 1 of our Phase 1 dose escalation study of PYX-201-101. A total of 80 patients were enrolled and treated with MICVO in the Part 1 dose-escalation portion of the study, as of the data cut-off of October 4, 2024, at dose levels ranging from 0.3 mg/kg to 8.0 mg/kg IV Q3W across multiple advanced solid tumor types. We identified a therapeutically active dose response range of 3.6 mg/kg – 5.4 mg/kg IV Q3W where we observed clinical benefit and a manageable safety profile. The dose-escalation schema and the number of patients treated at each dose level from trial initiation in March 2023 through the October 4, 2024 data cut-off are summarized in Figure 6 below. Figure 6 15 The preliminary efficacy analysis dataset included 65 patients, of whom 44 patients were treated within the dose range of 3.6 mg/kg to 5.4 mg/kg IV Q3W. As illustrated in Figure 7 below, tumor regression from baseline was observed across all nine tumor types evaluated in the study. Reductions in target lesion measurements were observed in multiple tumor types, with more pronounced responses noted in six tumor types of interest: including R/M HNSCC, HR+/HER2- breast cancer, NSCLC, ovarian, sarcoma and TNBC, at the therapeutically active dose response range of 3.6 mg/kg – 5.4 mg/kg IV Q3W. Figure 7 The R/M HNSCC patients demonstrated the strongest tumor regression response in the dataset. Among the six efficacy-evaluable, heavily pre-treated patients with R/M HNSCC, at the therapeutically active dose response range of 3.6 mg/kg – 5.4 mg/kg IV Q3W, the confirmed ORR was 50% (3/6) as assessed per RECIST v1.1, including one confirmed CR and two confirmed PRs with a DCR of 100%. The R/M HNSCC patients had received a median of four prior lines of systemic therapy in the advanced disease setting. Additionally, clinical activity was observed in patients with either HPV+ or HPV unrelated tumors as illustrated in Figure 8 below. Figure 8 16 PYX-201-101 Phase 1 Dose Expansion (Part 2) Monotherapy Study In January 2025, we initiated the dose expansion portion (Part 2) of the Phase 1 PYX-201-101 monotherapy study (NCT05720117). Part 2 is designed to further evaluate MICVO as a monotherapy at a dose of 5.4 mg/kg IV Q3W and to assess preliminary efficacy in R/M HNSCC. Based on observations from the dose-escalation study, 5.4 mg/kg IV Q3W presented an optimal benefit-risk profile within the efficacious dose range and was selected for dose expansion. Subsequent translational data indicated reduction in ctDNA TF after treatment with MICVO, particularly at the 5.4 mg/kg dose, supported a positive molecular response to MICVO, providing further validation of the dose selection strategy for dose expansion. In February 2025, the FDA granted Fast Track designation to MICVO for the monotherapy treatment of adult patients with R/M HNSCC whose disease has progressed following treatment with platinum-based chemotherapy and an anti-PD-(L)1 antibody. Fast Track designation is intended to facilitate the development and expedite the review of drugs that treat serious conditions and fill an unmet medical need. We completed target enrollment of approximately 40 patients in the Phase 1 monotherapy dose expansion study of MICVO in 2L+ R/M HNSCC in the first quarter of 2026 and are actively treating patients in two monotherapy R/M HNSCC cohorts at the 5.4 mg/kg IV Q3W dose. The dose expansion phase includes the following R/M HNSCC cohorts across sites in the United States (US), European Union (EU) and other countries: • Arm 1: MICVO monotherapy for 2L and 3L R/M HNSCC patients who have received prior platinum-based chemotherapy and prior PD-(L)1 inhibitor therapy. We expect to enroll approximately 20 patients in this expansion cohort at the 5.4 mg/kg IV Q3W dose; and • Arm 2: MICVO monotherapy for 2L and 3L R/M HNSCC patients who have received prior epidermal growth factor receptor (EGFR) directed therapy and prior PD-(L)1 inhibitor therapy. We expect to enroll approximately 20 patients in this expansion cohort at the 5.4 mg/kg IV Q3W dose. The clinical trial design of MICVO monotherapy in R/M HNSCC is summarized in Figure 9 below. Figure 9 PYX-201-101 Phase 1 Dose Expansion Monotherapy Study (Part 2) Preliminary Clinical Data In December 2025, we reported positive preliminary data from our ongoing Phase 1 monotherapy study evaluating MICVO in patients with 2L+ R/M HNSCC, based on a data cut-off date of November 3, 2025, which included all R/M HNSCC patients dosed at 5.4 mg/kg in Part 1 and in Part 2. As of the data cut-off date, 18 patients had been treated at the 5.4 mg/kg IV Q3W dose level, and 13 patients were efficacy-evaluable. All treated patients had received prior systemic therapy, including platinum-based chemotherapy, checkpoint inhibitor therapy, taxanes, and EGFR-targeted therapies. Patients had received a median of three prior lines of systemic therapy in the advanced disease setting. Patient demographics and the prior treatment characteristics of treated patients are illustrated in Figure 10 below. 17 Figure 10 Preliminary Efficacy The preliminary efficacy analysis dataset consisted of 13 efficacy-evaluable Part 1 and Part 2 patients with R/M HNSCC treated at 5.4 mg/kg IV Q3W. Figures 11 and 12 below present waterfall plots depicting the percentage change in target lesion size from baseline for individual patients, including stratification by expansion cohort (Arm 1 and Arm 2) and HPV status. Among the 13 efficacy-evaluable patients with R/M HNSCC treated at 5.4 mg/kg IV Q3W, the confirmed ORR was 46% (6/13) (one patient confirmed response after November 3, 2025 data cut-off), as assessed per RECIST v1.1, including one confirmed complete response. Confirmed responses were observed in both dose-expansion cohorts and in patients regardless of HPV status. The preliminary data also showed a DCR of 92% (12/13). One out of the 13 efficacy-evaluable patients experienced progressive disease. This patient had a verrucous subtype of HNSCC, a histologic variant that is generally managed with surgery and may demonstrate limited responsiveness to systemic therapy. Figure 11 18 Figure 12 Safety and Tolerability The preliminary safety data in Figure 13 summarizes key TRAEs observed as of the November 3, 2025 data cut-off date. Preliminary data indicated that MICVO was generally well tolerated. As of the data cut-off, 18 patients had been treated with MICVO at 5.4 mg/kg IV Q3W. TRAEs were reported in 89% (16/18) of patients. Grade 3 or higher TRAEs were reported in 56% (10/18) of patients. No Grade 4 ADC Payload treatment-related adverse events (TRAEs) of interest were observed, and no Grade 5 events occurred. TRAEs leading to treatment discontinuation occurred in 28% (5/18) of treated patients as of the November 3, 2025 data cut-off date. Figure 13 19 Impact of Body Weight on MICVO Tolerability and Dosing Optimization Strategies We observed a higher discontinuation rate and incidence of Grade ≥3 TRAEs at the 5.4 mg/kg dose level in high body weight patients (defined as at least 10% above AIBW). In the preliminary dataset, all patients (5/5) who experienced TRAEs leading to treatment discontinuation had high body weight, as shown in Figure 14. Several approved ADCs have demonstrated comparable associations among patient body weight, systematic drug exposure, and tolerability profiles. Figure 14 Following the November 3, 2025, data cut-off date and based on an integrated assessment of safety, pharmacokinetic, and exposure-response data, we implemented modified dosing strategies for MICVO in the ongoing study with the goal of mitigating adverse events and improving tolerability in higher body weight patients while preserving clinical efficacy. These strategies include dose capping and AIBW-based dosing, both intended to reduce variability in systemic drug exposure among heavier patients. Such approaches are consistent with precedent established by approved ADCs. For example, Padcev and Adcetris, which both have auristatin payloads similar to MICVO, incorporated dose caps for patients weighing more than 100 kg and have demonstrated improved tolerability while maintaining efficacy. Similarly, Elahere and Pfizer’s PDL1V ADC in clinical development, have implemented AIBW-based dosing to address tolerability findings in higher bodyweight patients. We believe the higher frequency of TRAEs observed in higher bodyweight patients treated with ADCs is primarily attributable to the nonlinear relationship between body weight and drug clearance. Due to this nonlinearity, higher bodyweight patients may experience disproportionately greater systemic exposure, creating an opportunity to enhance the benefit–risk profile through dose reduction without materially compromising efficacy. Preliminary PK/PD modeling presented in Figure 15 below, indicate both dose capping and AIBW dosing for MICVO effectively mitigate exposure in heavier patients. We plan to present clinical data in 2026 that informs this hypothesis with the intention of optimizing MICVO’s benefit-risk profile. 20 Figure 15 MICVO Monotherapy Next Milestone During the fourth quarter of 2025, we received feedback from the U.S. FDA regarding the clinical trial design for a planned pivotal monotherapy study in patients with 2L+ R/M HNSCC. Based on these interactions, we believe we have alignment with the FDA on key elements of the proposed study design. Our Part 2 dose-expansion phase of the PYX-201-101 monotherapy study has completed target enrollment of approximately 40 patients in 2L+ R/M HNSCC in the first quarter of 2026. We are continuing patient follow-up, monitoring clinical outcomes, and conducting related study activities. Updated MICVO Phase 1 monotherapy data in 2L+ R/M HNSCC are expected in mid-year 2026 and will include patients dosed at 5.4 mg/kg IV Q3W with a dose cap for patients with higher body weight, as well as patients previously dosed at 5.4 mg/kg IV Q3W TBW. The results are expected to include detailed analyses of the effect of the modified weight-based dosing strategy on safety and efficacy. AIBW dosing, which has demonstrated improved tolerability without apparent loss of activity in clinical studies of other antibody-drug conjugates, is being implemented in ongoing clinical studies as well. PYX-201-102 Combination Therapy Phase 1/2 Trial In November 2024, we entered into a Clinical Trial Collaboration and Supply Agreement with Merck & Co., Inc. (“Merck”) (known as MSD outside of the United States and Canada), pursuant to which we are conducting a Pyxis Oncology-sponsored clinical study evaluating MICVO in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab). Under the terms of the agreement, we are responsible for conducting and funding the study, and Merck is supplying pembrolizumab for use in the trial with no cost to us. The agreement does not provide Merck with any rights to MICVO outside of the collaboration study. In January 2025, we initiated the Phase 1/2 combination study with KEYTRUDA®, PYX-201-102, and we are actively enrolling patients. PYX-201-102 is a Phase 1/2, open label, global, multicenter, dose-escalation and dose-expansion study to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of MICVO in combination with pembrolizumab in patients with advanced solid tumors. Eligible patients include those with histologically or cytologically confirmed advanced solid tumors, including 1L R/M HNSCC, 2L+ R/M HNSCC, cervical cancer, gastric cancer, HR+/HER2- breast cancer, and locally advanced or metastatic TNBC. The Phase 1 portion of the trial consists of a dose-escalation phase designed to determine the recommended Phase 2 dose of MICVO in combination with pembrolizumab. The Phase 2 portion includes dose-expansion cohorts in selected tumor types to further evaluate safety and preliminary efficacy. Information regarding this study is available at ClinicalTrials.gov under identifier NCT06795412. The clinical trial design of the MICVO combination therapy in R/M HNSCC and other tumor types is summarized in Figure 16 below. 21 Figure 16 We are currently conducting the Part 1 dose-escalation portion of the PYX-201-102 Phase 1/2 study. Part 1 is designed to evaluate escalating dose levels of MICVO administered Q3W in combination with a fixed standard dose of pembrolizumab (200 mg IV Q3W). Three planned dose levels of MICVO are being evaluated in combination with pembrolizumab, ranging from 3.6 mg/kg to 5.4 mg/kg. The primary objective of the dose-escalation portion is to assess safety and tolerability and to identify the RP2D for further evaluation in the Phase 2 dose-expansion cohorts. Dose-escalation decisions are based on an evaluation of safety, dose-limiting toxicities, pharmacokinetics, and other clinical data. The study initiated dose escalation at 3.6 mg/kg of MICVO administered in combination with pembrolizumab 200 mg IV Q3W. The DESC has reviewed available safety data and cleared escalation through the 3.6 mg/kg and 4.4 mg/kg MICVO dose levels, each administered in combination with the fixed 200 mg dose of pembrolizumab. We are currently enrolling and dosing patients across several dose levels between 3.6 and 5.4 mg/kg of MICVO, in combination with pembrolizumab at the fixed dose of 200 mg IV Q3W, in order to accurately characterize the RP2D for MICVO in combination with pembrolizumab, subject to ongoing safety review, enrollment progress, and clinical data evaluation. PYX-201-102 Phase 1/2 Combination Therapy Preliminary Clinical Data In December 2025, we reported positive preliminary data from our ongoing MICVO Phase 1/2 combination study, PYX-201-102, evaluating MICVO at doses of 3.6 mg/kg and 4.4 mg/kg, each administered IV Q3W in combination with a fixed 200 mg dose of pembrolizumab, in patients with 1L/2L+ R/M HNSCC. The data were based on a cut-off date of November 3, 2025. As of the data cut-off, seven patients had been treated in the dose-escalation portion of the study, including four patients treated at 3.6 mg/kg and three patients treated at 4.4 mg/kg of MICVO, each in combination with pembrolizumab 200 mg IV Q3W. All treated patients had received prior systemic therapy. The patient population included: • Four patients with 1L R/M HNSCC, with a median of one prior systemic therapy administered in the neoadjuvant or adjuvant setting and • Three patients with 2L+ R/M HNSCC, with a median of three prior lines of therapy, some of which were received prior to the R/M setting. As shown in Figure 17 below, among the four patients with 1L R/M HNSCC, all had previously received platinum-based therapy administered with radiation in the adjuvant or definitive setting, and one patient had also received a prior taxane in the neoadjuvant setting. Among the three patients with 2L+ R/M HNSCC, all had previously received platinum-based therapy and prior checkpoint inhibitor therapy, and one patient had additionally received prior taxane therapy. 22 Figure 17 Preliminary Efficacy Among the seven response-evaluable patients as of the November 3, 2025 data cut-off, the confirmed ORR was 71% (5/7, one patient confirmed response after November 3, 2025 data cut-off) per RECIST v1.1. Responses were observed across a range of PD-L1 CPS, including patients with CPS≥1 and patients with CPS>20. Responses were also observed in patients who had previously received checkpoint inhibitor therapy and experienced disease progression while receiving checkpoint inhibitor treatment. All seven efficacy-evaluable patients demonstrated tumor regression from baseline measurements. Figures 18 and 19 below present waterfall plots depicting the percentage change in target lesion size from baseline for individual patients, including subgroup stratification by line of therapy (1L or 2L+ R/M HNSCC) and CPS score. Figure 18 23 Figure 19 Safety and Tolerability Figure 20 presents TRAEs reported as of the November 3, 2025 data cut-off date. Based on preliminary safety data from the seven patients treated in the dose-escalation cohorts evaluated at 3.6 mg/kg and 4.4 mg/kg of MICVO in combination with pembrolizumab, TRAEs were reported in 86% (6 of 7) of patients. No Grade 5 adverse events were reported. No Grade 3 or Grade 4 treatment-related adverse events associated with the ADC payload of MICVO were observed as of the data cut-off date. No TRAEs resulted in permanent treatment discontinuation. As of the data cut-off date, no overlapping toxicities between MICVO and pembrolizumab had been observed. Figure 20 24 MICVO Combination Therapy Next Milestone We are currently enrolling and dosing patients across several dose levels between 3.6 mg/kg and 5.4 mg/kg of MICVO, in combination with a fixed 200 mg IV Q3W, in order to accurately characterize the RP2D for MICVO in combination with pembrolizumab, subject to ongoing safety review, enrollment progress, and clinical data evaluation. We expect to report updated data from the PYX-201-102 study in patients with 1L/2L+ R/M HNSCC in the second half of 2026. Assets and Programs Available for Partnership or Collaboration In addition to MICVO, we have certain clinical programs, assets, and preclinical programs that are currently paused. While these programs and assets are paused, we are focusing our development efforts and resources towards the clinical development of MICVO. We are seeking partnership opportunities that maximize potential value of these programs for patients and for our shareholders. PYX-106 is an investigational fully human IgG1 Siglec-15-targeting antibody designed to block Siglec-15 mediated suppression of T-cell proliferation and function. PYX-106 has high binding affinity to a unique epitope and high potency. By binding and blocking Siglec-15 activity on myeloid cells and tumors, our Siglec-15 targeting antibody is designed to enhance immune cell mediated tumor cell killing. We licensed worldwide rights other than in Greater China (mainland China, Hong Kong, Macau and Taiwan) to PYX-106 from Biosion. In December 2024, after analysis of the program, PYX-106 was deprioritized and resources were reallocated toward advancing MICVO. At the time of deprioritization, the Phase 1 study of PYX-106, called PYX-106-101, was not complete. PYX-106-101 enrolled 45 patients with advanced solid tumors, with 41 patients being evaluable, and PYX-106 was observed as generally safe and well-tolerated across all tested doses, ranging from 0.5 mg/kg – 22.5 mg/kg. At the time of deprioritization, MTD had not been established, we decided to suspend further clinical investment in PYX-106 and not to open Part 2 dose expansion phase of the study. Sotigalimab or PYX-107 , acquired as part of the acquisition of Apexigen Inc. (Apexigen), is a CD40 agonist with demonstrated anti-cancer activity in patients with several cancer indications. PYX-107 has been evaluated in more than 500 patients in clinical trials and demonstrated strong activity, including rapid, deep and durable responses and a favorable tolerability profile, across multiple difficult-to-treat tumor types. In a Phase II trial, PYX-107 in combination with nivolumab has demonstrated strong activity in melanoma patients who are refractory to anti-PD-(L)1, with a 15.2% PR rate and a 30.3% stable disease rate along with a favorable tolerability profile. The FDA has granted Orphan Drug Designation for PYX-107 for the treatment of soft tissue sarcoma (STS), esophageal and gastroesophageal junction (EGJ) cancers and PDAC. PYX-203 , licensed from Pfizer, is an investigational ADC that targets and binds to the interleukin-3 receptor, also known as CD123, a rapidly internalizing target that is overexpressed in hematologic cancers by leukemic blasts and stem cells. After internalization, its highly potent cyclopropylpyrroloindoline (CPI) payload is enzymatically released and trafficked to the nucleus, where it crosslinks DNA. CPI is engineered for enhanced tolerability and may allow PYX-203 to reach a broader patient population. CPI is resistant to drug efflux pumps and could confer superior cancer-killing activity. The antibody is also engineered to have a modified Fc region to mitigate off-tumor toxicity. PYX-102 is an investigational immune-therapeutic that targets killer cell lectin-like receptor subfamily G member 1 (KLRG1), an inhibitory receptor expressed on T cells and NK cells. Its ligands, E- and N-cadherin are expressed in numerous solid cancers. By blocking KLRG1 signaling, PYX-102 may relieve immune inhibition in these tumors while rescuing KLRG1-mediated suppression of human CD8+ T cells. PYX-102 has significant potential as a monotherapy and in combination treatment strategies. Our Technology Platforms We are capitalizing on years of industry innovation and advancement in ADC platforms to develop and design our product candidates. Our MICVO product candidate was built utilizing the FACT Platform, initially licensed from Pfizer in December 2020, before securing an exclusive license to the FACT Platform in October 2022. The FACT Platform leverages over a decade of investment by Pfizer in refining the technical components of ADCs to improve the clinical properties of ADCs. Using our expertise in site-specific antibody conjugation, we are developing next-generation ADCs with customized linker-payload combinations aimed at increasing stability and, consequently, a reduced off target side-effect profile potentially enhancing the Therapeutic Index (TI). The acquisition of Apexigen enhanced our ADC capabilities with the addition of Apexigen’s antibody-discovery platform (APXiMAB) Platform, to use with our FACT Platform to support and potentially accelerate our existing ADC initiatives and our end-to-end capabilities to design and produce novel next-generation ADC candidates with improved potency, stability and tolerability. 25 The APXiMAB Platform was used to enable the discovery of multiple protein therapeutic product candidates against a variety of molecular targets, including targets that are difficult to generate antibodies with conventional antibody technologies. In addition to certain product candidates that we wholly own, several product candidates that were discovered through the use of the APXiMAB Platform are in clinical development by our licensees. The most advanced of these programs is Novartis’ Beovu® (brolucizumab-dbll) product, which received FDA approval in 2019 and is marketed in over 70 countries. For the Simcere suvemcitug/Enzeshu® program, during the year, the Company has sold its royalty rights under Simcere Royalty Agreement. Other than already approved programs (i.e. Simcere’s Enzeshu®, Novartis’ Beovu®) there is no guarantee that any of the other product candidates discovered using our APXiMAB Platform, whether developed by us or our licensees, will receive regulatory approval. Target Catalog and Discovery Efforts We have a large proprietary target catalog that we have assembled through both our own discovery activities and through an exclusive license from the University of Chicago for the work on immunotherapy targets out of Dr. Thomas Gajewski’s laboratory. We are also building a large “cold” tumor target discovery database leveraging several human tumor databases. The target catalog is based upon findings from an in vivo mouse model system which examined tumor tissue for functional and dysfunctional T cells based on the ability of the T cells to produce the cytokine IL-2. Furthermore, since 4-1BB and LAG3 positive T cells do not secrete IL-2, the CD8+ T cells were sorted based on cell surface marker expression i.e., 4-1BB and LAG3, which further defined functional or dysfunctional T cells. Gene expression analysis identified upregulated cell surface molecules in dysfunctional cells which included well established markers such as PD1, CTLA4, and TIM3 and many other novel targets were identified based on bioinformatics and deep biological rationale. Our cold tumor target discovery database used RNA-seq transcriptome analysis of human tumor databases to identify potential novel targets involved in regulation of T cell function and/or infiltration leading to cold tumors. We have supplemented this database with additional resources which we continue to mine to identify additional novel targets for immunomodulation. These cold tumor targets are potentially dominant immune suppressors that are expressed across a variety of tumor associated cells, including immune cells, tumors cells, and stroma, offering the potential to uncover novel immuno-oncology (IO) mechanisms and additional novel targets for our ADC platform. We have large opportunities to advance product candidates based on the target catalog, however, we have chosen not to conduct additional discovery efforts to refocus our development efforts and resources toward clinical development of MICVO. Competition The development and commercialization of therapeutic biological products is highly competitive. We compete with a variety of multinational biopharmaceutical companies and specialized biotechnology companies, as well as technology being developed at universities and other research institutions. Our competitors have developed, are developing or will develop product candidates and processes competitive with our product candidate. Competitive therapeutic treatments include those that have already been approved or licensed and accepted by the medical community and any new treatments that enter the market. We believe that a significant number of products are currently under development, and may become commercially available in the future, for the treatment of conditions for which we may try to develop product candidates. Biotechnology and pharmaceutical industries, including the oncology subsector, are characterized by rapidly evolving technologies, intense competition and strong defense of intellectual property and proprietary technologies. Any product candidate that we successfully commercialize may be competitive with currently marketed therapies and any new therapies commercialized in the future. We are aware of several companies that are developing cancer immunotherapies and ADCs. Many of these companies are well-capitalized, have significant clinical experience, and may include our existing or future collaborators. In addition, these companies compete with us in recruiting scientific and managerial talent and the patient pool available for participation in clinical trials which could negatively impact our ability to execute our business plan. If our product candidate is licensed, it will compete with a range of therapeutic treatments that are either in development or currently marketed. Many companies are active across various stages of development in the oncology subsector and are marketing and developing products that employ similar ADC and immunotherapy approaches. As of February 2026, there were approximately 900+ ADCs in clinical or preclinical development worldwide, of which the vast majority are being developed for the treatment of various cancer indications. Additionally, there are several large and small companies working on various immunotherapy approaches for treatment of cancer. Multiple companies are also involved in the development of ADC therapeutics and immunotherapies, including, but not limited to, AbbVie Inc., Abcure, Inc., ADC Therapeutics SA, Alligator Bioscience AB, Astellas Pharma, Inc., AstraZeneca plc, Celldex Therapeutics, Inc., Daiichi Sankyo Company, Ltd., Eucure Biopharma, a subsidiary of Biocytogen, Genentech, Inc., Gilead Sciences, Inc, GlaxoSmithKline, plc, Johnson & Johnson, Lyvgen Biopharma, Nextcure, Inc., Pfizer, Philogen S.p.A., Merck Sharpe & Dohme (MSD), Corbus Pharmaceuticals, and Rakuten Medical, Inc. 26 We may also face competition from alternative therapeutic modalities, such as cell therapies, bispecific antibodies, vaccines, radiopharmaceuticals and small molecules that are being developed for the same cancer types that we are targeting with our pipeline candidate. These approaches could achieve regulatory approval before our product candidate or prove to be more effective, safer, or convey other advantages over any products resulting from our technology. They could potentially result in shifts in treatment paradigms eroding or reducing the addressable market available to our product candidate. We could also face competition with respect to specific targets, including the target of our ADC, MICVO, EDB+FN, by Philogen S.p.A., a Swiss based Biotechnology company, focused on generating antibody-cytokine fusions (immunocytokines) against cancers, using the L19 antibody specific to the EDB domain of Fibronectin fused to TNF, a potent inflammatory cytokine, which could pursue similar indications targeting EDB and stand out as the first non-ADC therapy pursuing EDB+FN. There are other emerging agents in key indications of interest including R/M HNSCC. Genmab’s EGFR and LGR5 targeting biclonal, petosemtamab, Bicara’s EGFR/TGF-beta targeting bifunctional, ficerafusp alfa (BCA101), and Johnson and Johnson’s EGFR and cMET bispecific antibody, amivantamab, are notable competitors that are targeting patient populations of interest to MICVO and pose a potentially significant threat to our clinical development strategy. Additionally, Corbus Pharmaceutical’s nectin-4 targeting ADC, CRB-701 has shown preliminary efficacy data and is a direct competitor given similarity in payload (MMAE) to MICVO, and comparable patient populations and clinical development timelines in R/M HNSCC. Other competitors may also include agents targeting specific segments such as HPV+ HNSCC, namely NeoTrail Therapeutics (formerly Hookipa)’s and PDS Biotech’s vaccines and agents such as Nanobiotix’s radioenhancer that may be used earlier in the treatment sequence. With the approval of pembrolizumab in the peri-operative setting based on Keynote-689, use of IO in the neoadjuvant and adjuvant settings may shift how HPV patients are treated in earlier lines of therapy. The implementation of using IO in the earlier disease settings could impact patient segmentation and treatment choices in the R/M setting. Furthermore, ADCs such as Gilead’s TROP-2 ADC, sacituzumab govitecan, Pfizer’s Nectin-4 targeting ADC, enfortumab vedotin and AZ’s AZD9592, a dual targeting ADC against EGFR and cMET are in clinical development in HNSCC. Enfortumab vedotin is currently pursuing a 1L HNSCC trial in combination with pembrolizumab thus adding to the crowded landscape of combo studies in the frontline setting. Additional competition may arise from other combination regimens being evaluated including but not limited to ficlatuzumab + cetuximab (2L), ivonescimab + ligufalimab (1L, CPS>1) and LN-145 + pembrolizumab (1L). Additionally, there is a wide array of activity in the development of immunotherapies for oncology which may be competitive with our preclinical discovery programs. Furthermore, if our product candidate is approved in oncology indications such as breast cancer, hematological and other cancers, they may compete with existing approaches to treating cancer including surgery, radiation, and drug therapy, including conventional chemotherapy, biological products, and targeted drug small molecule therapies. Our competitors may possess greater scientific, research and development capabilities, as well as greater financial, technical, manufacturing, marketing, sales and supply resources or experience than we do. These competitors may compete with us on the basis of establishing clinical trial sites and patient registration, recruiting and retaining qualified scientific and management personnel, and acquiring new technologies that may be complementary to, or necessary for, our programs. If we achieve regulatory approval, commercial opportunity for our product candidate may be dependent on the ability of our competitors to develop new products that may be more effective, safer, or less expensive than any products that we may develop. Our competitors may succeed in developing competing products before we do, obtaining marketing approval for products and gaining acceptance for such products in the same markets that we are targeting. Smaller or earlier-stage companies that seek collaborative arrangements with large and established companies, may prove to be significant competitors. In addition, our ability to compete may be affected by the availability of reimbursement from government and other third party payors. Competitive factors affecting the success of our programs, if approved, will likely be based on their safety and effectiveness, the timing and scope of marketing approvals, the availability and cost of supply, the depth of marketing and sales capabilities, and reimbursement coverage, among other considerations. Competitive products may make any products we develop obsolete owing to treatment paradigm shifts or noncompetitive, reducing the addressable market before we recover the expense of developing and commercializing our product candidate. Such competitors could also recruit our employees, which could negatively impact our level of expertise and our ability to execute our business plan. We believe that our ability to successfully compete will depend on, among other things: • our ability to develop and protect therapeutics that are more effective and safer than competing products; • our ability to innovate with rapidly evolving technologies; • the ease with which our products can be administered and the extent to which patients accept relatively new routes of administration; • the timing and scope of regulatory licenses for these products; 27 • the price of our product candidate and whether coverage and adequate levels of reimbursement are available under health insurance plans; • our ability to utilize any abbreviated licensure pathways; and • the length of time we are granted market exclusivity for any product candidate we may develop that is licensed as a biological product under a Biologics License Application (BLA). Chemistry, Manufacturing and Controls The manufacture of our ADCs and monoclonal antibodies requires significant scientific expertise, specialized technical capabilities, and substantial financial and operational resources. We do not own or operate any current Good Manufacturing Practice (cGMP)-compliant manufacturing facilities and currently have no plans to establish such facilities. Accordingly, we rely, and expect to continue to rely, on third-party contract development and manufacturing organizations (CDMOs) for the manufacture of our product candidates for preclinical and clinical development and, if approved, for commercial supply. Our reliance on third-party manufacturers limits our direct control over manufacturing capacity, production schedules, costs, and compliance with cGMP and other regulatory requirements. Although we maintain quality agreements and technical oversight processes, we are dependent on the performance and compliance of our CDMOs. If any of our third-party manufacturers fail to comply with applicable regulatory requirements, experience quality or performance issues, encounter capacity constraints, or cease operations, our development timelines and potential commercialization efforts could be materially and adversely affected. In addition, certain raw materials, components, and intermediates used in the manufacture of our product candidates may be sourced from single suppliers, and we may not maintain fully qualified alternate suppliers for all materials or manufacturing steps. Any interruption in the supply of such materials, including due to manufacturing failures, regulatory actions, business disruptions, or geopolitical events, could delay development activities or increase costs. The manufacture of ADCs, in particular, involves complex multi-step processes, including monoclonal antibody production, linker and payload synthesis, and conjugation. Variability in process performance, including deviations in raw material specifications or process parameters, may result in reduced yields, batch failures, or the need for investigations and corrective actions. Such events could require additional manufacturing runs, process optimization, or comparability analyses and may necessitate regulatory notifications or submissions. As part of our product development strategy, we rely on our internal scientific expertise and proprietary know-how, as well as the technical capabilities and trade secrets of our third-party manufacturing partners. We maintain agreements with our CDMOs that include customary confidentiality, intellectual property, and quality provisions designed to protect our proprietary rights and ensure compliance with applicable regulatory standards. We believe that outsourcing manufacturing enables us to maintain a capital-efficient and flexible operating model by avoiding the significant investment required to build and operate our own manufacturing facilities and infrastructure. At the same time, we have established internal personnel and governance processes with experience in technical development, manufacturing sciences, analytical development, quality assurance, cGMP compliance, and project management to oversee our CDMOs and to manage manufacturing data and regulatory documentation in support of our development and potential commercialization activities. Commercialization Plans We currently retain worldwide rights to our lead product and while we intend to commercialize this asset upon FDA approval in the US, we may have opportunities to leverage partnerships to extend the reach of our products into geographies outside the US. We currently have no sales, marketing, or commercial product distribution capabilities. We intend to build our own specialized sales and marketing organization over time to support the commercialization of any approved product candidate. We may also pursue collaboration, co-promotion, distribution and/or other marketing arrangements with one or more third parties to commercialize our product candidate in the United States, and potentially other regions. We may also pursue these arrangements for situations in which a larger sales and marketing organization is necessary to realize the full commercial value of any approved wholly owned or collaboration product candidate. Licensing and Collaboration Agreements The University of Chicago Agreement In April 2020, we entered into a license agreement (the University License Agreement) with the University of Chicago (the University) to obtain an exclusive license under certain patents resulting from research performed, in-part, by our scientific founder, Dr. Thomas Gajewski, as well as a non-exclusive license to certain know-how and materials. Under the terms of the license, we have the exclusive global right to develop and commercialize products that are covered by a valid claim of a licensed patent, incorporate or use the licensed know-how and materials or are known to assess, modulate or utilize the activity of certain specified biological targets. 28 In partial consideration for the license from the University, we issued to the University 48,919 shares of our common stock in 2020. Pursuant to the University License Agreement, we are obligated to pay to the University an annual maintenance fee of $10,000 commencing on the third anniversary of the effective date, potential development and commercial milestones of up to an aggregate of $7.7 million as well as running royalties on net sales of licensed products at varying rates ranging from less than a percent to the low single digits, subject to a minimum annual royalty ranging from $1.0 million to $3.0 million during certain years following the first commercial sale of a licensed product. The Company assessed the milestone and royalty events under the University License Agreement as of December 31, 2025 and 2024, and determined that no such amounts were required. Our royalty obligations apply on a licensed product-by-licensed product and country-by-country basis until: (1) for licensed products covered by a valid claim of a licensed patent in a given country, the expiration of such valid claims; and (2) for all other licensed products, 10 years from the first commercial sale of a licensed product in a given country. We are also obligated to pay the University a percentage of certain sublicensing revenue ranging from low- to mid-teens based on the date of entering into the applicable sublicense. Under the University License Agreement, we are obligated to use commercially reasonable efforts to develop and bring licensed products to market, meet certain preclinical and clinical development milestones by specific dates, and promote and sell licensed products after receipt of regulatory approval, subject to certain free and payment-based extensions. The University controls prosecution of the licensed patents at our cost and we have the first right to enforce the licensed patents subject to the University’s backup enforcement rights. The University License Agreement will remain in effect on a licensed product-by-licensed product basis until the expiration of all royalty obligations with respect to a licensed product, unless terminated in accordance with the following: (1) by the University upon 30 days’ prior written notice for any uncured payment breaches or 90 days’ prior written notice for all other uncured breaches; (2) by the University upon certain insolvency events or dissolution by us or any affiliate; or (3) by us in full or with respect to a particular licensed product at the end of the calendar quarter following the calendar quarter when we provide written notice of termination. Pfizer Inc. Agreement In December 2020, the Company entered into a license agreement (as amended, the “Pfizer License Agreement”) with Pfizer Inc. (“Pfizer”) for worldwide development and commercialization rights to ADC product candidates directed to certain licensed targets, including MICVO and PYX-203, and products containing the ADC product candidates. The Company’s rights are exclusive with respect to certain patents owned or controlled by Pfizer covering the licensed ADCs. The initial licensed targets include CD123 and EDB+FN and the Company has the option to expand the scope of its license to add additional licensed targets that have not been licensed to a third party or are not the subject of a Pfizer ADC development program. The Pfizer License Agreement became effective in March 2021 and the Company paid a combined $25.0 million for the license fee, consisting of an upfront cash payment of $5.0 million and issued 12,152,145 shares of Series B convertible preferred stock, which was converted into 1,911,015 shares of its common stock upon the initial public offering (“IPO”) in October 2021, with a value of $20.0 million to Pfizer. On October 6, 2022, the Company entered into an amended and restated license agreement (the “A&R License Agreement”) with Pfizer, which amends and restates the Pfizer License Agreement. Pursuant to the A&R License Agreement, Pfizer granted to the Company exclusive worldwide rights under Pfizer’s FACT Platform technology to develop and commercialize ADC product candidates directed to certain licensed targets, including MICVO and PYX-203, and products containing the ADC product candidates. Additional ADC targets may be licensed for a nominal upfront payment and milestones. In accordance with the terms of the A&R License Agreement, the Company issued 2,229,654 shares of its common stock to Pfizer in October 2022, paid $8.0 million to Pfizer in January 2023 and issued 1,811,594 shares of its common stock to Pfizer in March 2023. Further, pursuant to the A&R License Agreement, the Company is obligated to pay future contingent payments including development, regulatory and commercial milestones as well as running royalties on net sales of licensed products at varying rates. The Company assessed the milestone and royalty events under the A&R License Agreement as of December 31, 2025 and 2024, and determined that no such amounts were required. We are also obligated to pay future contingent payments, including development, regulatory, and commercial milestone up to an aggregate of $665 million for the first four licensed ADCs. In addition, we are required to pay future contingent payments including development, regulatory and commercial milestones for ADCs to each additional licensed target beyond the first four licensed ADC targets developed and commercialized via the FACT Platform. Additionally, if ADC licensed products are launched, we will pay Pfizer tiered royalties on net sales of licensed products in varying royalty rates ranging from low single digits to mid-teens. Our royalty obligations apply on a licensed product-by-licensed product and country-by-country basis from first commercial sale until the latest to occur of: (1) 12 years from first commercial sale; (2) the expiration of all regulatory or data exclusivity; and (3) the expiration of the last valid claim of a licensed patent covering the licensed product in a country. We are also obligated to pay Pfizer a percentage of certain sublicensing revenue ranging from low-double digits to twenty percent based on the stage of development of the licensed product at the time of entering into the applicable sublicense. 29 Under the Pfizer License Agreement, we are obligated to use commercially reasonable efforts to nominate a clinical candidate within four years of a target becoming a licensed target. We are also required to use commercially reasonable efforts to develop and seek regulatory approval for at least one licensed product directed to each licensed target in the United States and at least one other major market country (France, Germany, Italy, Japan, Spain and the United Kingdom), and to commercialize any licensed product in each such country after receiving regulatory approval. We control prosecution and enforcement with respect to any exclusively licensed patents, and Pfizer has prosecution and enforcement rights if we elect not to exercise such rights. The Pfizer License Agreement will remain in effect until the expiration of the last to expire royalty term, unless terminated in accordance with the following: (1) by either party for the other party’s material breach if such party fails to cure such breach within the specified cure period; (2) by either party upon certain insolvency events of the other party; or (3) prior to receipt of the first regulatory approval for a licensed product, by us for any reason upon 90 days’ prior written notice, or after receipt of the first regulatory approval for a licensed product, by us for any reason upon one year’s prior written notice. License Agreement with Biosion USA, Inc. On March 28, 2022, we entered into a license agreement (the Biosion License Agreement) with Biosion USA, Inc. (Biosion) pursuant to which we obtained an exclusive, worldwide (other than Greater China (mainland China, Hong Kong, Macau and Taiwan)), license for development, manufacturing and commercialization rights for BSI-060T, a Siglec-15 targeting antibody, an IO product candidate (now referred to as PYX-106), and products containing the licensed compound. Under the terms of the Biosion License Agreement, each party granted to the other party a right of first offer to obtain an exclusive license in the other party’s territory (Greater China for Biosion and the rest of the world for us) to develop, manufacture and commercialize any bi-specific or multi-specific antibody any antibody-drug conjugate controlled by a party or its affiliate that inhibits, modulates or binds to Siglec-15 as an intended mechanism of action. Pursuant to the Biosion License Agreement, we paid an upfront fee of $10.0 million in March 2022 and are obligated to pay future contingent payments including development, regulatory and commercial milestones up to an aggregate of $217.5 million in case of normal approval and $222.5 million in case of Accelerated Approval. Additionally, if products are launched, we will pay Biosion tiered royalties on net sales of licensed products in varying royalty rates ranging from low single digits to low teens. In December 2024, the Company paused the clinical development of PYX-106. The Company assessed the milestone and royalty events involving the Biosion License Agreement as of December 31, 2025 and 2024, and determined that no such amounts were required. Our royalty obligations apply on a licensed product-by-licensed product and country-by-country basis from first commercial sale until the latest to occur of: (1) 12 years from first commercial sale; (2) the expiration of all regulatory or data exclusivity; and (3) the expiration of the last valid claim of a licensed patent covering the licensed product in a country. We are also obligated to pay Biosion a percentage of certain sublicensing revenue ranging from low-double to mid-double digits based on the stage of development of the licensed product at the time of entering into the applicable sublicense. Under the Biosion License Agreement, we are obligated to use commercially reasonable efforts to clinically develop and seek regulatory approval for at least one licensed product in the licensed territory, and to commercialize such licensed product following receipt of regulatory approval. We control prosecution and enforcement with respect to the licensed patents in the licensed territory. The Biosion License Agreement will remain in effect on a licensed product-by-licensed product and country-by-country basis until the expiration of the applicable royalty term, unless terminated in accordance with the following: (1) by either party for the other party’s material breach if such party fails to cure such breach within the specified cure period; (2) by either party upon certain insolvency events of the other party; (3) by us for scientific or safety reasons; (4) any time following completion of our first clinical trial for a licensed product, by us for convenience; or (5) by Biosion if we cease development and commercialization activities for licensed products for a specified period of time, subject to certain exceptions. Out-License Relationships In August 2023, we completed the acquisition of Apexigen contemplated by the Merger Agreement, with Apexigen surviving as a wholly owned subsidiary of the Company. Upon the Merger Agreement, we assumed all out-licensing agreements of Apexigen. The assumed agreements consist of licenses with several biopharmaceutical companies that are developing product candidates that were discovered using our APXiMAB platform, which has been important to prosecuting the full value of our platform. We believe the licenses for the programs for the development of product candidates we have generate and demonstrate the productivity and utility of our platforms and position us to receive meaningful milestone and royalty payments if those product candidates are approved and successfully commercialized. Described below are the out-license relationships and the related agreements under which we may receive milestone or royalty payments. 30 Simcere License and Collaboration Agreement In December 2008, Epitomics (Apexigen’s predecessor) and Jiangsu Simcere Pharmaceutical R&D Co., Ltd. (Simcere) entered into a license and collaboration agreement (the Simcere Agreement) for the development and commercialization of suvemcitug (BD0801) for oncology in China. Suvemcitug is a humanized anti-VEGF monoclonal antibody molecule derived from APXiMAB technology. Simcere is responsible for conducting the development and commercialization of suvemcitug in China at its cost. Under the terms of the Simcere Agreement, Apexigen had, and now we have, reserved the right to develop and commercialize suvemcitug outside of China at our discretion. If we develop and commercialize suvemcitug outside of China, we will share with Simcere costs incurred and revenue earned outside of China. Under the Simcere Agreement, Simcere has an exclusive, royalty-bearing license (without the right to sublicense) to Apexigen's rights in certain intellectual property to develop and commercialize suvemcitug in the field of oncology therapeutics in China. Simcere granted Apexigen a non-exclusive, royalty-free, worldwide license (without the right to sublicense) to improvements derived from suvemcitug using the intellectual property licensed to Simcere for any purpose outside of China and for purposes outside of oncology therapeutics in China. Intellectual property created in the collaboration program with Simcere is jointly owned by Apexigen and Simcere. In January 2024, Simcere announced that the Phase 3 clinical trial of suvemcitug for injection combined with chemotherapy in patients with recurrent, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer met its primary endpoints of the progression-free survival. In March 2024, Simcere announced the New Drug Application (NDA) for suvemcitug for injection was accepted by the China National Medical Products Administration (NMPA). On June 30, 2025, the National Medical Products Administration (NMPA) of China (formerly SFDA) granted final regulatory approval for suvemcitug in China. Upon suvemcitug approval by the NMPA, the Company received a $3 million regulatory approval milestone under the Simcere Agreement. On December 2025, we entered into an amendment to the License and Collaboration Agreement (the Simcere Royalty Agreement) with Simcere, pursuant to which we relinquished our rights to future royalties on the net sales of Enzeshu® to Simcere for a one-time amount of $11.0 million and four semi-annual installments of $175,000 each. Notwithstanding the foregoing amendment, the Simcere Agreement otherwise remains in full force and effect. T-Mab/Mabwell Agreement In May 2008, Epitomics and Jiangsu T-Mab Biotechnology Ltd., Co. (T-Mab) entered into a license, co-development and contract manufacture agreement (the T-Mab Agreement) for the development and commercialization of therapeutic candidates in two therapeutic programs, each directed to a specified target for specified fields, including VEGF for the treatment of ocular diseases, in China. The Company assessed the milestone and royalty events involving Mabwell as of December 31, 2025 and determined that no such amounts were receivable. Mabwell (Shanghai) Bioscience Co., Ltd. (Mabwell) acquired T-Mab in 2015. Mabwell is responsible for conducting the development and commercialization of the therapeutic candidates in China. We may, at our discretion, develop and commercialize such therapeutic candidates outside of China; however, we must pay Mabwell a royalty on sales of such therapeutic candidates made outside of China if we do so. Under the T-Mab Agreement, Mabwell was granted an exclusive, royalty-bearing, perpetual license (without the right to sublicense) to its rights in certain intellectual property that it licensed from Epitomics to develop and commercialize such therapeutic candidates. Mabwell is obligated to pay us a mid-single-digit percentage royalty on net sales of such therapeutic candidates in China. If we choose to commercialize such therapeutic candidates outside of China, we would be obligated to pay Mabwell a mid-single-digit percentage royalty on net sales of such therapeutic candidates outside of China that we sell directly to end users and a mid-single-digit percentage of revenue we receive as sublicense fees, milestone payments and royalties related to the sale of such therapeutic candidate. Each party’s obligations to pay royalties to the other party continue until 15 years after the first commercial sale of licensed product in each party’s respective territory. The term of the T-Mab Agreement expired in May 2013; however, Mabwell’s royalty payment obligations under the agreement survive expiration. The royalty term for 9MW0211, an anti-VEGF antibody licensed under the T-Mab Agreement, will begin with the first commercial sale in China and end after a low two-digit number of years. Mabwell is currently in Phase 3 development of 9MW0211. Toray Sublicense Agreement In May 2012, Apexigen and Toray Industries, Inc. (Toray), entered into a non-exclusive sublicense agreement (the Toray Agreement) under which Apexigen granted Toray a non-exclusive, worldwide sublicense, with the right to grant further sublicenses, to develop and commercialize drug product candidates that Toray developed using antibodies created using the APXiMAB platform that target certain molecules to use in the development of its drug product candidates. Under the Toray Agreement, Toray paid an upfront fee and agreed to pay certain development- and regulatory-related milestone payments and a low single-digit percentage royalty on net sales of licensed products by Toray or its affiliates. The Company assessed the milestone and royalty events involving Toray as of December 31, 2025 and determined that 31 no such amounts were receivable. Toray is also obligated to pay us a mid-teens percentage of certain payments Toray receives from sublicensees under the Toray Agreement, which payments may limit Toray’s obligations to pay the milestone payments described above. Subject to certain termination rights, including Toray’s right to terminate the agreement for convenience upon 60 days’ prior written notice, the Toray Agreement continues on a product-by-product and country-by-country basis until 10 years after the first commercial sale of such product in such country. Upon expiration or early termination of the agreement, Toray’s sublicense and any further sublicenses granted by Toray will automatically terminate. Toray is currently in Phase 2 development of TRK-950, an antibody licensed under the Toray Agreement. Intellectual Property Our intellectual property is critical to our business, and we strive to protect it, including by obtaining and maintaining patent protection in the U.S. and internationally for our product candidates, new therapeutic approaches, platform technologies, potential methods of use in our indications of interest and other inventions that are important to our business. We also rely on trade secrets and proprietary know-how to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection. Our patent portfolio includes patents and patent applications that are exclusively licensed from the University of Chicago, Pfizer and Biosion, and patents and patent applications that are wholly owned by us. Our patent portfolio includes patents and patent applications that cover our product candidates MICVO (formerly PYX-201), PYX-203, PYX-106, PYX-107 and PYX-102, and the use of these candidates for therapeutic purposes in certain territories. Our proprietary technology has been developed primarily through internal development efforts and relationships with academic institutions, Pfizer, Biosion and contract research organizations. For our product candidates, we will, in general, initially pursue patent protection covering compositions of matter and methods of use. Throughout the development of our product candidates, we seek to identify additional means of obtaining patent protection that would potentially enhance commercial success, including through additional methods of use for particular indications, process of making, formulation and dosing regimen-related claims. For all patent applications, we determine claiming strategy on a case-by-case basis. Advice of counsel and our business model and needs are always considered. We file patent applications containing claims for protection of useful applications of our proprietary technologies and any products, as well as new applications and/or uses we discover for existing technologies and products, assuming these are strategically valuable. We continuously reassess the number and type of patent applications, as well as the existing patent claims to ensure that maximum coverage and value are obtained for our processes and compositions, given existing patent office rules and regulations. Further, claims may be modified during patent prosecution to meet our intellectual property and business needs. We recognize that the ability to obtain patent protection and the degree of such protection depends on a number of factors, including the extent of the prior art, the novelty and non-obviousness of the invention, and the ability to satisfy the enablement requirement of the patent laws. The patent positions of immuno-oncology companies like ours are generally uncertain and involve complex legal, scientific and factual questions. Consequently, we may not obtain or maintain adequate patent protection for any of our current or future product candidates or for our platform technologies. We cannot predict whether the patent applications we are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient proprietary protection from competitors. Any patents that we hold may be challenged, circumvented or invalidated by third parties. Regardless of the coverage we seek under our existing patent applications, there is always a risk that an alteration to the product or process may provide sufficient basis for a competitor to avoid infringement claims. In addition, the coverage claimed in a patent application can be significantly reduced before a patent is issued, and courts can reinterpret patent scope after issuance. Moreover, many jurisdictions, including the United States, permit third parties to challenge allowed or issued patents in administrative proceedings, which may result in further narrowing or even cancellation of patent claims. Moreover, we cannot provide any assurance that any patents will be issued from our pending or any future applications or that any current or future issued patents will adequately protect our products. In total, our patent portfolio, including patents licensed from the University of Chicago, Pfizer and Biosion, and patents owned by us, comprises 29 different patent families, filed in various jurisdictions worldwide, including families directed to compositions of matter for antibodies and antibody-drug conjugates, families directed towards the compositions, manufacture, and use, of antibodies and antibody-drug conjugates generally, families directed towards methods of identifying patients for treatment with compositions of antibodies and antibody-drug conjugates and subsequently treating said patients, and families directed to methods of treating cancer and identifying potential targets. 32 MICVO (formerly PYX-201) Patent Families, Status, and Potential Expiration MICVO is covered by a growing portfolio of patent families, some of which are in-licensed from Pfizer, some of which we have sole ownership of, and one of which we co-own. Details, status, and potential expiration dates of MICVO patent families are summarized below: MICVO Antibody-Drug Conjugate Composition of Matter (Drug Product) Patent Coverage MICVO Related Patent Families – Constructs, Methods, and Components MICVO Anti-EDB+FN Antibody-Drug Conjugate Composition of Matter and Methods of Using the Same . We have exclusively licensed from Pfizer a patent family for antibodies and antibody-drug conjugates that bind to the extra domain B splice variant of fibronectin, including the composition of matter for MICVO and methods of using MICVO in treating certain cancer including NSCLC, colorectal cancer, PDAC and generic breast cancer, that includes granted patents in Australia, Austria, Belgium, Brazil, Bulgaria, China, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Great Britian, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Latvia, Lithuania, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Russia, Serbia, Singapore, Slovak Republic, Slovenia, South Korea, Spain, Sweden, Switzerland, Turkey, and the United States, and pending applications in Australia, Brazil, Canada, China, European Patent Organization (Europe), Hong Kong, Israel, Japan, Mexico, Singapore, South Africa, and the United States. The 20-year term of the patents in this family runs through 2037, absent any available patent term adjustments or extensions. 33 Methods of using MICVO - Constructs and Compositions for Treating EDB+FN Expressing Disease and Disorders in Certain Cancer Indications. We have sole ownership of a patent family for constructs, compositions, and methods of treating EDB+FN expressing diseases and disorders, including but not limited to HNSCC, sarcoma, TNBC, HR+ breast cancer, ovarian cancer, and thyroid cancer, with MICVO and similar constructs, that includes a pending PCT application. The 20-year term of this patent family runs through 2045, absent any available patent term adjustments or extensions. Dosage and Treatment Regimens of MICVO. We have sole ownership of a patent family for dosage and treatment regimens of MICVO and similar constructs, that includes a pending PCT application. The 20-year term of this patent family runs through 2045, absent any available patent term adjustments or extensions. Combination Therapies including MICVO . We have sole ownership of two patent families for certain drug combinations with MICVO, that include four provisional patent applications. The 20-years terms for these patent families run through 2046, absent any available patent term adjustments or extensions. Combination of MICVO and Pembrolizumab. We have joint ownership of a patent family for the combination of MICVO and pembrolizumab in certain cancer indications at certain dose levels. The 20-year term of this patent family runs through 2046, absent any available patent term adjustments or extensions. Cytotoxic Peptides and Antibody-Drug Conjugates Thereof . We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward cytotoxic pentapeptides, including the auristatin 0101 (Aur0101) payload and MC-VC-PABC-Aur0101 linker-payload (vc0101, pelidotin) found in MICVO, and to antibody-drug conjugates thereof, that includes granted patents in Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Czech Republic, Denmark, Finland, France, Germany, Great Britain, Greece, Hong Kong, Hungary, Iceland, India, Indonesia, Ireland, Israel, Italy, Japan, Luxembourg, Malaysia, Mexico, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Portugal, Romania, Russia, Saudi Arabia, Singapore, Slovak Republic, Slovenia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey, and the United States. The 20-year term of the patents in this family runs through 2032, absent any available patent term adjustments or extensions. Antibodies and Antibody Fragments for Site-Specific Conjugation . We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward polypeptides, antibodies, and antigen-binding fragments thereof, that comprise a engineered cysteine for site-specific conjugation, including the K290C engineered cysteine found in MICVO, that includes granted patents in Australia, Canada, Colombia, India, Israel, Malaysia, Mexico, Saudi Arabia, South Africa, and Taiwan, and a pending application in Europe. The 20-year term of the patents in this family runs through 2036, absent any available patent term adjustments or extensions. Engineered Antibody Constant Regions for Site-Specific Conjugation and Methods and Uses Therefor . We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward antibodies, and antigen-binding portions thereof, engineered to introduce amino acids for site-specific conjugation, including the kK183C engineered cysteine found in MICVO, that includes granted patents in Canada, EPO (Unitary Patent), France, Germany, Great Britain, Ireland, Italy, Japan, Spain, Switzerland, and the United States, and a pending application in Canada and Japan. The 20-year term of the patents in this family runs through 2032, absent any available patent term adjustments or extensions. Composition of Matter Patents for Additional Assets (excluding MICVO) PYX-203 Anti-CD123 Antibody-Drug Conjugate . We have exclusively licensed from Pfizer a patent family for antibodies and antibody-drug conjugates that specifically bind to CD123, that includes granted patents in Australia, Canada, China, Colombia, Hong Kong, India, Israel, Japan, Mexico, Russia, South Korea, Taiwan, and the United States, and pending applications in Brazil, China, Europe, Japan, New Zealand, Singapore, South Africa, and the United States, that claim the composition of matter and certain methods of use with respect to PYX-203. The 20-year term of the patents in this family runs through 2038, absent any available patent term adjustments or extensions. PYX-106 Anti-Siglec-15 Antibody . We have exclusively licensed from Biosion USA, Inc. a patent family for monoclonal antibodies that specifically bind human Siglec15, including PYX-106, that includes granted patents in Australia, Canada, China, Israel, Japan, Malaysia, New Zealand, Russia, Saudi Arabia, South Korea, and the United States, and pending applications in Australia, Brazil, Egypt, Europe, Hong Kong, India, Indonesia, Mexico, New Zealand, Philippines, Singapore, South Africa, United Arab Emirates, and the United States. The 20-year term of the patents in this family runs through 2041, absent any available patent term adjustments or extensions. 34 PYX-107A/B “Sotigalimab” CD40 Agonist Antibodies . Through our acquisition of Apexigen, Inc. we have acquired sole ownership of two patent families for high affinity CD40 agonist monoclonal antibodies and related compositions, including PYX-107 (also known as sotigalimab) which may be used in any of a variety of therapeutic methods for the treatment of cancer and other diseases. The first patent family includes granted patents in Australia, Belgium, Brazil, Canada, China, France, Germany, Great Britain, Hong Kong, India, Italy, Japan, Mexico, New Zealand, Russia, Singapore, South Africa, South Korea, Spain, Switzerland, and the United States, with a pending application in Israel. The 20-year term of this first patent family runs through 2032, absent any available patent term adjustments or extensions. The second patent family includes granted patents in Australia, Belgium, China, Denmark, France, Germany, Great Britain, Hong Kong, India, Ireland, Italy, Japan, Netherlands, New Zealand, Norway, South Africa, South Korea, Spain, Sweden, Switzerland, and the United States, with pending applications in Canada, Europe, and the United States. The 20-year term of this second patent family runs through 2033, absent any available patent term adjustments or extension. PYX-102 Anti-KLRG1 Antibody. We have sole ownership of a patent family for monoclonal antibodies that specifically bind human KLRG1, that includes a pending applications in Australia, Canada, China, Europe, Japan, and the United States. The 20-year term of this patent family runs through 2044, absent any available patent term adjustments or extensions. PYX-205 Antibody-drug Conjugates and Methods of Use. We have sole ownership of a patent family for certain ADC compositions with payload optionality, that includes a pending provisional application in the United States. The 20-year term of this patent family, if converted, runs through 2047, absent any available patent term adjustments or extensions. Certain Methods Patents Related to Compositions of Matter PYX-107D Methods of Treating Cancer with CD-40 Agonists . Through our acquisition of Apexigen we have acquired sole ownership of a patent family for methods of identifying a sub-population of cancer patients amenable for a combination therapy with a CD40 agonist and one or more chemotherapy drugs and subsequently treating the sub-population of cancer patients with said combination therapy, that includes pending patent applications in Canada, China, Europe, Japan, and the United States. The 20-year term of the patents in this family runs through 2042, absent any available patent term adjustments or extensions. PYX-107F Biomarkers for CD40 Agonist Therapy . Through our acquisition of Apexigen we have acquired sole ownership of a patent family for biomarkers and other characteristics for predicting tumor responsiveness to CD40 agonist therapy in melanomas, and related kits, compositions, and methods of treating said melanomas, including PD-(L)1 refractory melanomas, that includes pending applications in Europe and the United States. The 20-year term of the patents in this family runs through 2042, absent any available patent term adjustments or extensions. PYX-002 Site Specific Ligand-Payload Conjugates . We have sole ownership of a patent family for ligand-payload conjugates, and compositions and use thereof for treating diseases, disorders, or conditions, such as cancers, autoimmune diseases, or infectious diseases, that includes pending applications in Europe and the United States. The 20-year term of the patents in this family runs through 2043, absent any available patent term adjustments or extensions. Antibody-Drug Candidate Patent Rights Purification of Antibody-Drug Conjugates Using a Sodium Phosphate Gradient . We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture useful in antibody-drug conjugates generally, directed toward methods of removing high molecular weight species, in particular aggregates, from antibody-drug conjugate preparations, by contacting preparations of the antibody-drug conjugate reaction mixture with a hydroxyapatite resin and selectively eluting the antibody-drug conjugate from the resin using a gradient comprising sodium phosphate, that includes granted patents in France, Germany, Great Britain, Ireland, Italy, Spain, and the United States, and a pending application in the United States. The 20-year term of the patents in this family runs through 2036, absent any available patent term adjustments or extensions. Platform Patent Rights Stability-Modulating Linkers for Use with Antibody-Drug Conjugates . We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward stability-modulating linker components used to make these stability-modulated antibody-drug conjugates, that includes granted patents in Australia, Brazil, Canada, China, France, Germany, Great Britain, India, Italy, Japan, Mexico, Russia, South Korea, Spain, and the United States, and a pending application in Mexico. The 20-year term of the patents in this family runs through 2035, absent any available patent term adjustments or extensions. 35 Synergistic Auristatin Combinations . We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward combinations of an auristatin or an auristatin-based antibody-drug conjugate with second active agents including PI3K/mTOR inhibitors, MEK inhibitors, taxanes, or other anti-cancer agents, that includes granted patents in the United States and Japan. The 20-year term of the patents in this family runs through 2035, absent any available patent term adjustments or extensions. Capped and Uncapped Antibody Cysteines, and Their Use in Antibody-Drug Conjugation . We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward antibody production process in which engineered unpaired cysteine residues are post-translationally modified and capped with particular chemical entities, which capped antibodies are well suited to further site-specific conjugation steps to form antibody-drug conjugates, that includes granted patents in Australia, Brazil, China, France, Germany, Great Britain, India, Ireland, Israel, Italy, Japan, Mexico, Russia, South Korea, Spain, Switzerland, and the United States, and pending applications in Canada and Europe. The 20-year term of the patents in this family runs through 2036, absent any available patent term adjustments or extensions. Large Scale Production Process for Capped and Uncapped Antibody Cysteines and Their Use in Therapeutic Protein Conjugation . We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward optimizing production of selectively capped, and uncapped, cysteines on antibodies by manipulation of cell growth conditions, that includes granted patents in South Korea and the United States, and no pending applications. The 20-year term of the patents in this family runs through 2038, absent any available patent term adjustments or extensions. Bifunctional Cytotoxic Agents . We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward cytotoxic dimers comprising CBI-based and/or CPI-based sub-units, and antibody-drug conjugates comprising such dimers, that includes granted patents in Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Czech Republic, Denmark, Finland, France, Germany, Great Britain, Greece, Hong Kong, Hungary, Iceland, India, Indonesia, Ireland, Israel, Italy, Japan, Luxembourg, Malaysia, Mexico, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Portugal, Romania, Russia, Saudi Arabia, Singapore, Slovak Republic, Slovenia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey, the United States and Venezuela, and a pending application in Argentina. The 20-year term of the patents in this family runs through 2035, absent any available patent term adjustments or extensions. Engineered Polypeptide Conjugates and Methods for Making Thereof Using Transglutaminase . We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward engineered polypeptide conjugates comprising acyl donor glutamine-containing tags and amine donor agents, that includes granted patents in Canada, Japan, and the United States, and a pending application in Europe. The 20-year term of the patents in this family runs through 2031, absent any available patent term adjustments or extensions. Antibody-Drug Conjugates with High Drug Loading . We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward transglutaminase-mediated antibody-drug conjugates with high anti-body-drug ratio, that includes granted patents in Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, Denmark, Finland, France, Germany, Great Britain, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Luxembourg, Mexico, Netherlands, Poland, Portugal, Romania, Russia, Slovak Republic, Slovenia, South Korea, Spain, Sweden, Switzerland, Turkey, and the United States, and no pending application. The 20-year term of the patents in this family runs through 2035, absent any available patent term adjustments or extensions. Methods in Immuno-Oncology Methods and Compositions Related to T-Cell Activity . We have exclusively licensed from the University of Chicago a patent family for methods for treating patients with immunotherapy based on the identification of the patient as having non-anergic T cells after measuring expression levels of various genes that includes granted and pending patents in the United States. The 20-year term for patents in this family runs through 2034, absent any available patent term adjustments or extensions. Beta-catenin Inhibitors in Cancer Immunotherapy . We have exclusively licensed from the University of Chicago a patent family for methods for treating solid tumor cancers that includes granted patents in the United States, and no pending applications. The 20-year term for patents in this family runs through 2036, absent any available patent term adjustments or extensions. Dysfunctional Antigen-specific CD8+ T Cells in the Tumor Microenvironment . We have exclusively licensed from the University of Chicago a patent family for methods of treating cancer comprising administering an agent that specifically targets dysfunctional tumor antigen-specific CD8+T cells that includes pending applications in Canada, and Europe, and a granted patent in the United States. The 20-year term for patents in this family runs through 2038, absent any available patent term adjustments or extensions. 36 Patent Term and Term Extensions Individual patents have terms for varying periods depending on the date of filing of the patent application or the date of patent issuance and the legal term of patents in the countries in which they are obtained. Generally, utility patents issued for applications filed in the United States, and most countries around the world, are granted a term of 20 years from the earliest effective filing date of a non-provisional patent application. In addition, in certain instances, the term of a U.S. patent can be extended to recapture a portion of the United States Patent and Trademark Office (USPTO) delay in issuing the patent as well as a portion of the term effectively lost as a result of the FDA regulatory review period. However, as to the FDA component, the restoration period cannot be longer than five years, and is typically less, and the restoration period cannot extend the patent term beyond 14 years from FDA approval. In addition, only one patent applicable to an approved drug is eligible for the extension, and only those claims covering the approved drug, a method for using it, or a method of manufacturing may be extended. Similar provisions are available in Europe and other foreign jurisdictions to extend the term of a patent that covers an approved drug. We will, in general, pursue available patent term extensions in the U.S. and in foreign jurisdictions that provide for patent term extensions, however, there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of whether such extensions should be granted, and if granted, the length of such extensions. All taxes, annuities or maintenance fees for a patent, as required by the USPTO and various foreign jurisdictions, must be timely paid in order for the patent to remain in force during this period of time. The actual protection afforded by a patent may vary on a product-by-product basis, from country to country, and can depend upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions and the availability of legal remedies in a particular country and the validity and enforceability of the patent. Our patents and patent applications may be subject to procedural or legal challenges by others. We may be unable to obtain, maintain and protect the intellectual property rights necessary to conduct our business, and we may be subject to claims that we infringe or otherwise violate the intellectual property rights of others, which could materially harm our business. For more information, see the section titled “Risk Factors—Risks Related to Our Intellectual Property.” Trademarks and Know-How In connection with the ongoing development and advancement of our product candidate in the United States and various international jurisdictions, we seek to create protection for our marks and enhance their value by pursuing trademarks where available and when appropriate. In addition to patent and trademark protection, we rely upon trade secrets and know-how and continuing technological innovation to develop and maintain our competitive position. We seek to protect our proprietary information, in part, using confidentiality agreements with our commercial partners, collaborators, employees and consultants and invention assignment agreements with our employees and selected consultants. We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems. While we have confidence in these individuals, organizations and systems, agreements or security measures may be breached, and our trade secrets and other proprietary information may be disclosed. We may not have adequate remedies for any breach and could lose our trade secrets and other proprietary information through such a breach. In addition, our trade secrets may otherwise become known or be independently discovered by competitors. To the extent that our consultants, contractors or collaborators use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting trade secrets, know-how and inventions. Our commercial success will also depend in part on not infringing the proprietary rights of third parties. In addition, we have licensed rights under proprietary technologies of third parties to develop, manufacture and commercialize specific aspects of our future products and services. It is uncertain whether the issuance of any third party patent would require us to alter our development or commercial strategies, alter our processes, obtain licenses or cease certain activities. The expiration of patents or patent applications licensed from third parties or our breach of any license agreements or failure to obtain a license to proprietary rights that we may require to develop or commercialize our future technology may have a material adverse impact on us. If third parties prepare and file patent applications in the United States that also claim technology to which we have rights, we may have to participate in interference proceedings in the USPTO to determine priority of invention. For more information regarding the risks related to our intellectual property, please see “Risk Factors—Risks Related to Our Intellectual Property.” 37 Government Regulation The research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record keeping, serialization and tracking, promotion, advertising, distribution and marketing, post approval or licensure monitoring and reporting, and export and import, among other things, of our product candidates are extensively regulated by governmental authorities in the United States and in other countries and jurisdictions, including the EU. In the United States, the FDA regulates biological products under the Federal Food, Drug, and Cosmetic Act (FDCA) and its implementing regulations, and the Public Health Service Act (PHSA) and its implementing regulations. Failure to comply with the applicable U.S. requirements may subject us to administrative or judicial sanctions, such as the FDA’s refusal to approve a Biologics License Application (BLA), warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions and/or criminal prosecution. Preclinical Studies Before testing any biologic product candidate in humans, the product candidate undergoes preclinical testing. Preclinical tests, also referred to as non-clinical studies, include laboratory evaluations of the product chemistry, pharmacology, toxicity and formulation, as well as animal studies to assess the pharmacokinetics, metabolism, bio-distribution, elimination and toxicity of the product candidate. The conduct of the preclinical tests and formulation of the compounds for testing must comply with federal regulations and requirements and certain preclinical trials must conform to the FDA’s Good Laboratory Practice requirements (GLP). The results of preclinical testing, manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, among other things, must be submitted to the FDA as part of an IND that must be reviewed and cleared by the FDA before clinical testing can begin. The IND will become effective 30 days after the FDA receives the application, unless the FDA raises concerns or questions related to the investigations in the application and places the trial on clinical hold. In this situation, the IND sponsor must resolve any outstanding FDA concerns before clinical trials can proceed. As a result, submission of an IND may or may not result in the FDA authorizing clinical trials to commence. Clinical Development The FDA and comparable regulatory agencies in state and local jurisdictions and in foreign countries impose substantial requirements upon the clinical development, manufacture and marketing of pharmaceutical products. These agencies and other federal, state and local entities regulate, among other things, research and development activities and the testing, manufacture, export, import, quality control, marketing approval, safety, effectiveness, labeling, storage, record keeping, promotion, advertising, distribution and marketing and post-marketing safety reporting. The process required by the FDA before product candidates may be marketed in the U.S. generally involves the following: • non-clinical laboratory and animal tests, some of which must be conducted in accordance with GLP ; • submission of an Investigational New Drug (IND) application, which contains results of non-clinical studies (e.g., laboratory evaluations of the chemistry, formulation, stability and toxicity of the product candidate), together with Investigator’s Brochure, manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, and must become effective before human clinical trials may begin; • approval by an independent Institutional Review Board (IRB) or ethics committee for each clinical trial site before each trial may be initiated; • adequate and well-controlled human clinical trials conducted in accordance with the protocol and Good Clinical Practice (GCP) to establish the safety and efficacy of the product candidate for its proposed intended use; • for drug products, submission of a New Drug Application (NDA) to the FDA for commercial marketing, or generally of a supplemental New Drug Application (sNDA), for approval of a new indication if the product is already approved for another indication; • for biotherapeutic products, submission of a Biologics License Application (BLA) to the FDA for commercial marketing, or generally a supplemental Biologics License Application (sBLA) for approval of a new indication if the product is already approved for another indication; • pre-approval inspection of manufacturing facilities and selected clinical investigators, clinical trial sites and/or Pyxis Oncology as the clinical trial sponsor for their compliance with cGMP and GCP, respectively; • payment of user fees for FDA review of an NDA or BLA unless a fee waiver applies; 38 • agreement with the FDA on the final labeling for the product and design and implementation of any required Risk Evaluation and Mitigation Strategy; • if the FDA convenes an advisory committee, satisfactory completion of the advisory committee review; and • FDA approval of the NDA or sNDA, or BLA or sBLA. Clinical Trials Clinical trials involve the administration of the biologic product candidate to volunteers or patients under the supervision of qualified investigators in accordance with GCP requirements, which include the requirement that all research patients provide their informed consent for their participation in any clinical trial. Clinical trials are conducted under protocols detailing the objectives of the study, dosing procedures, inclusion and exclusion criteria, study procedures, parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. Further, the study protocol and informed consent information for patients in clinical trials must also be submitted to an IRB for approval covering each institution at which the clinical trial will be conducted. The IRB will consider, among other requirements, rationale for conducting the trial, clinical trial design, patient informed consent, ethical factors, the safety and rights of human patients and the possible liability of the institution. The FDA can temporarily or permanently halt a clinical trial at any time, or impose other sanctions, if it believes that the clinical trial is not being conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical trial patients. The IRB may also require the clinical trial at a particular site be halted, either temporarily or permanently, or impose other conditions, for failure to comply with GCP or the IRB’s requirements. For purposes of NDA or BLA approval, human clinical trials are typically conducted in three sequential phases that may overlap or be combined: • Phase 1 clinical trials, which involve the initial introduction of a new drug product candidate into humans, are initially conducted in a small number of volunteers or patients to assess the product candidate for early tolerability, safety, pattern of drug absorption, distribution and metabolism, the mechanism of action in humans, and may include studies where investigational drugs are used as research to explore biological phenomena or disease processes. • Phase 2 clinical trials typically are conducted in a limited patient population with a specific disease in order to provide enough data to evaluate the preliminary efficacy, optimal dosage, and common short-term side effects and risks associated with the drug. Multiple phase 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive phase 3 clinical trials. • Phase 3 clinical trials typically are larger scale, multicenter, well-controlled trials conducted on patients with a specific disease to gather additional information about effectiveness and safety across a higher number of patients and evaluate the overall benefit-risk relationship of the product candidate following earlier phase evaluations, which will have provided preliminary evidence suggesting an effective dosage range and acceptable safety profile for the product candidate. Phase 3 trials are also intended to provide an adequate basis for the product labeling if it is approved. Post approval clinical trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These clinical trials may be conducted to fulfill mandatory conditions of product approval or used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up. The mandatory studies are used to confirm clinical benefit in the case of drugs approved under the accelerated approval regulations or to provide additional clinical safety or efficacy data for “full” approvals. Failure to promptly conduct and complete mandatory Phase 4 clinical trials could result in withdrawal of approval for products approved under accelerated approval regulations. A therapeutic product candidate being studied in clinical trials may be made available for treatment of individual patients, intermediate-size patient populations, or for widespread treatment use under an expanded access protocol, under certain circumstances. Pursuant to the 21st Century Cures Act, or Cures Act, which was signed into law in December 2016, the manufacturer of one or more investigational products for the diagnosis, monitoring, or treatment of one or more serious diseases or conditions is required to make available, such as by posting on its website, its policy on evaluating and responding to requests for individual patient access to such investigational product. Additionally, on May 30, 2018, the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 was signed into law. The law, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase 1 clinical trial and that are undergoing investigation for FDA approval. Under certain circumstances, eligible patients can seek treatment without enrolling in clinical trials and without obtaining FDA authorization under an FDA expanded access program; however, manufacturers are not obligated to provide investigational new drug products under the current federal right to try law. 39 Disclosure of Clinical Trial Information Under the PHSA, sponsors of certain clinical trials of FDA-regulated products are required to register and disclose certain clinical trial information. Information related to the product, patient population, phase of investigation, trial sites and investigators, and other aspects of the clinical trial are then made public as part of the registration on a public registry (clinicaltrials.gov) maintained by the U.S. National Institutes of Health (the NIH). Sponsors are also obligated to disclose the results of their clinical trials after completion. Competitors may use this publicly available information to gain knowledge regarding the progress of development programs. Information for certain clinical trials also must be publicly disclosed within certain time limits on the clinical trial registry and results databank maintained by the NIH. Expedited Development and Review Programs The FDA has a number of programs intended to expedite the process for developing and reviewing promising drugs, or to provide for the approval of a drug on the basis of a surrogate endpoint. Generally, drugs that are eligible for these programs are those for serious or life-threatening conditions, those with the potential to address unmet medical needs and those that offer meaningful benefits over existing treatments. Examples of such programs include Fast Track Designation, Breakthrough Therapy Designation, Priority Review designation and Accelerated Approval, and the eligibility criteria of and benefits of each program vary: • Fast Track is a process designed to facilitate the development and expedite the review of drugs intended to treat a serious or life-threatening conditions that demonstrate the potential to address unmet medical needs, by providing, among other things, potential actions to expedite development and review, and rolling review, which allows submission of individually completed sections of an NDA for FDA review before the entire submission is completed. The FDA may revoke the Fast Track Designation if it believes that the designation is no longer supported by data emerging in the clinical trial process. • Breakthrough Therapy Designation is a process designed to expedite the development and review of drugs intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence demonstrates that the drug may have substantial improvement on one or more clinically significant endpoints over existing therapies. Drugs designated as breakthrough therapies are also eligible for other actions to expedite review. The FDA will seek to ensure the sponsor of a Breakthrough Therapy product candidate receives intensive guidance on an efficient drug development program, intensive involvement of senior managers and experienced staff on a proactive, collaborative and cross-disciplinary review, and rolling review. • Priority Review is designed to shorten the review period for drugs that are intended to treat a serious conditions and, if approved or licensed, would provide a significant improvement in safety or effectiveness. The FDA intends to take action on a Priority Review marketing application within six months of receipt, compared to 10 months for regular review submissions. • Accelerated Approval provides for an earlier approval of a new drug intended to treat a serious or life-threatening disease or condition and that provides a meaningful therapeutic benefit over existing treatments and demonstrates an effect on a surrogate endpoint, or an intermediate clinical endpoint, which is considered reasonably likely to predict a clinical benefit. As a condition of approval, the FDA requires that a sponsor of a product candidate receiving Accelerated Approval perform post-marketing clinical trials or provide data on established clinical endpoints from the same trial to confirm the clinical benefit as predicted by the surrogate marker trial and may require that these studies be underway prior to approval. In addition, the FDA requires, as a condition for Accelerated Approval, the submission of promotional materials in advance, which could adversely impact the timing of the commercial launch of the product. The FDA can also withdraw an Accelerated Approval on an expedited basis provided it follows certain procedures. Fast Track Designation, Breakthrough Therapy Designation, Priority Review and Accelerated Approval do not change the standards for licensure but may expedite the review process. In February 2025, the FDA granted Fast Track Designation for use of MICVO for the treatment of adults with R/M HNSCC whose disease has progressed following treatment with platinum-based chemotherapy and an anti-PD-(L)1 antibody. Additionally, with respect to oncology products, the FDA may review applications under the Real-Time Oncology Review (RTOR) program established by the FDA’s Oncology Center of Excellence. The RTOR program, which allows an applicant to pre-submit components of the NDA or BLA to allow the FDA to review clinical data before the complete filing is submitted, aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible, while maintaining and improving review quality. Drugs considered for review under the RTOR program must be likely to demonstrate substantial improvements over available 40 therapy, which may include drugs previously granted breakthrough therapy designation for the same or other indications and must have straight-forward study designs and endpoints that can be easily interpreted. Orphan Drugs Under the Orphan Drug Act, the FDA may grant orphan drug designation to therapeutic candidates (drugs or biological products) intended to treat a disease or condition that affects fewer than 200,000 individuals in the U.S. (or for which there is no reasonable expectation that the cost of developing and making available in the U.S. for such disease or condition will be recovered from sales in the U.S.). To be eligible for orphan drug designation, the FDA must not have previously approved a drug considered the “same drug,” as defined in the FDA’s orphan drug regulations, for the same orphan-designated indication or the sponsor of the subsequent drug must provide a plausible hypothesis of clinical superiority over the previously approved same drug. Upon receipt of Orphan Drug Designation, the sponsor is eligible for tax credits for certain clinical trial expenses, waiver of pediatric studies, and an exemption from the BLA application fee. In addition, upon marketing approval, an Orphan Drug Designation could be eligible for seven years of market exclusivity if no drug considered the same drug was previously approved for the same orphan condition (or if the subsequent drug is demonstrated to be clinically superior to any such previously approved same drug). Such orphan drug exclusivity, if awarded, would only block the approval of any drug considered the same drug for the same orphan indication. Orphan drug exclusivity does not prevent the FDA from approving a different biological product for the same disease or condition, or the same biological product for a different disease or condition. In May 2023, the FDA granted Orphan Drug Designation for use of MICVO in the treatment of pancreatic cancer. Additional controls for biologics To help reduce the increased risk of the introduction of adventitious agents, the PHSA emphasizes the importance of manufacturing controls for products whose attributes cannot be precisely defined. The PHSA also provides authority to the FDA to immediately suspend biologics licenses in situations where there exists a danger to public health, to prepare or procure products in the event of shortages and critical public health needs, and to authorize the creation and enforcement of regulations to prevent the introduction or spread of communicable diseases within the United States. After a BLA is approved, the product may also be subject to official lot release as a condition of approval. As part of the manufacturing process, the manufacturer is required to perform certain tests on each lot of the product before it is released for distribution. If the product is subject to official release by the FDA, the manufacturer submits samples of each lot of product to the FDA together with a release protocol showing a summary of the lot manufacturing history and the results of all of the manufacturer’s tests performed on the lot. The FDA may also perform certain confirmatory tests on lots of some products, such as viral vaccines, before allowing the manufacturer to release the lots for distribution. In addition, the FDA conducts laboratory research related to the regulatory standards on the safety, purity, potency, and effectiveness of biological products. As with drugs, after approval of a BLA, biologics manufacturers must address any safety issues that arise, are subject to recalls or a halt in manufacturing, and are subject to periodic inspection after approval. FDA Review of BLAs After completion of the required clinical testing, a BLA is prepared and submitted to the FDA. FDA approval of the BLA is required before marketing of the product may begin in the United States. The BLA must include the results of all preclinical, clinical and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture and controls. The cost of preparing and submitting a BLA is substantial. The submission of most BLAs is additionally subject to a substantial application user fee, currently $4,682,003 for BLAs requiring clinical data for fiscal year 2026, and the manufacturer and sponsor under an approved BLA are also subject to annual program fees, currently $442,213 (fiscal year 2026) for each prescription product. Sponsors of applications for drugs granted Orphan Drug Designation are exempt from these user fees. The FDA has 60 days from its receipt of a BLA to determine whether the application will be accepted for filing based on the Agency’s threshold determination that it is sufficiently complete to permit substantive review. The FDA may request additional information rather than accept a BLA for filing. In this event, the application must be resubmitted with the additional information. The resubmitted application is also subject to review before the FDA accepts it for filing. If the application is accepted for review, the FDA reviews the application to determine, among other things, whether a product is safe and effective for its intended use and whether the manufacturing controls are adequate to assure and preserve the product's identity, strength, quality, and purity. The FDA has agreed to certain performance goals in the review of BLAs to encourage timeliness. Applications for standard review biological products are meant to be reviewed within ten months; applications for Priority Review drugs are meant to be reviewed in six months. Priority Review can be applied to biological products that the FDA determines offer major advances in treatment or provide a treatment where no adequate therapy exists. The review process for both standard and Priority Review may be extended by the FDA for three additional months (“major amendment”) to consider certain late-submitted information, or information intended to clarify information already provided in the submission. 41 The FDA is required to refer an application for a novel biological product to an advisory committee or explain why such referral was not made. An advisory committee is typically a panel that includes clinicians and other experts—for review, evaluation and a recommendation as to whether the application should be approved. The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations. Before approving a BLA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. Additionally, the FDA will inspect the facility or the facilities at which the drug is manufactured. The FDA will not license the product unless compliance with cGMP is satisfactory, and the application meets the appropriate standard. A BLA must include data that demonstrate that the biological product is safe, pure and potent. After the FDA evaluates the BLA and accompanying information and the manufacturing facilities, it issues either an approval letter or a complete response letter. An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing, or information, in order for the FDA to reconsider the application. If, or when, those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the BLA, the FDA will issue an approval letter. The FDA has committed to reviewing such re-submissions in two or six months depending on the type of information included. Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval. If the FDA approves a product, it may limit the approved indications for use for the product; require that contraindications, warnings or precautions be included in the product labeling; require that post-marketing studies, including Phase 4 clinical trials, be conducted to further assess the drug’s safety after licensure; require testing and surveillance programs to monitor the product after commercialization; or impose other conditions, including distribution restrictions or other risk management mechanisms, which can materially affect the potential market and profitability of the product. As a condition of BLA licensure, the FDA may require a risk evaluation and mitigation strategy (REMS) to help ensure that the benefits of the biological product outweigh the potential risks. REMS can include medication guides, communication plans for healthcare professionals and elements to assure safe use (ETASU). ETASU can include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring and the use of patient registries. The requirement for a REMS can materially affect the potential market and profitability of the drug. Moreover, product licensure may require substantial post approval testing and surveillance to monitor the drug’s safety or efficacy. Once granted, product licenses may be withdrawn if compliance with regulatory standards is not maintained, or problems are identified following initial marketing. The FDA may prevent or limit further marketing of a product based on the results of post-market studies or surveillance programs. Changes to some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and FDA approval, as applicable, of a new BLA or supplement before the change can be implemented. A BLA supplement for a new indication typically requires similar non-clinical and CMC data to that in the original application, and the FDA uses the same procedures and actions in reviewing supplements as it does in reviewing BLAs. Post-Licensure FDA Requirements Following approval of a new product, the manufacturer and the approved product are subject to continuing regulation by the FDA, including, among other things, monitoring and record keeping activities, reporting of adverse experiences, complying with promotion and advertising requirements, which include restrictions on promoting products for unapproved uses or patient populations (known as “off-label use”) and limitations on industry sponsored scientific and educational activities. Although physicians may prescribe legally available products for off-label uses, manufacturers may not market or promote such uses. Prescription drug and biologic promotional materials must be submitted to the FDA in conjunction with their first use. Further, if there are any modifications to the biologic, including changes in indications, labeling or manufacturing processes or facilities, the applicant may be required to submit and obtain FDA approval of a new BLA or sBLA, which may require the development of additional data or preclinical studies and clinical trials. The FDA may also place other conditions on approvals including the requirement for a REMS to assure the safe use of the product. If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS. The FDA will not approve the BLA without an approved REMS, if required. A REMS could include medication guides, physician communication plans or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products. Product approvals may be withdrawn for non-compliance with regulatory standards or if problems occur following initial marketing. 42 FDA regulations require that products be manufactured in specific facilities and in accordance with cGMP regulations. We rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of our products in accordance with cGMP regulations. These manufacturers must comply with cGMP regulations that require, among other things, quality control and quality assurance, the maintenance of records and documentation and the obligation to investigate and correct any deviations from cGMP. Manufacturers and other entities involved in the manufacture and distribution of approved drugs or biologics are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP requirements and other laws, including applicable product tracking and tracing requirements. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain cGMP compliance. The discovery of violations, including failure to conform to cGMP regulations, could result in enforcement actions, and the discovery of post approval problems with a product may result in restrictions on a product, manufacturer or holder of an approved BLA, including recall. Biosimilars and Reference Product Exclusivity The Biologics Price Competition and Innovation Act of 2009 (BPCIA) created an abbreviated approval pathway for biological product candidates shown to be highly similar (“biosimilar”) to or interchangeable with an FDA licensed reference biological product. Biosimilarity, which requires there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, can generally be shown through analytical studies, animal studies, and a clinical study or studies. Interchangeability requires that a product is biosimilar to the reference product, and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for products that are administered multiple times to an individual, the interchangeable biosimilar and the reference biological product may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biological product. A product shown to be biosimilar or interchangeable with an FDA-approved reference biological product may rely in part on the FDA’s previous determination of safety and effectiveness for the reference product for approval, which can potentially reduce the cost and time required to obtain approval to market the product. Complexities associated with the larger, and often more complex, structures of biological products, as well as the processes by which such products are manufactured, pose significant hurdles and have slowed implementation of the BPCIA by the FDA. Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years following the date that the reference product was first licensed by the FDA. In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date on which the reference product was first licensed. During this 12-year period of reference product exclusivity, another company may obtain FDA licensure and market a competing version of the reference product if the FDA approves a full BLA for the competing product containing that applicant’s own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of its product. The BPCIA also created certain exclusivity periods for biosimilars approved as interchangeable products. At this juncture, it is unclear whether products deemed “interchangeable” by the FDA will, in fact, be readily substituted by pharmacies, which are governed by state pharmacy law. The BPCIA is complex and continues to be interpreted and implemented by the FDA. In addition, government proposals have sought to reduce the 12-year reference product exclusivity period. Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation. As a result, the ultimate implementation of the BPCIA remains subject to significant uncertainty. Patent Term Extension Depending upon the timing, duration, and specifics of the FDA approval and BLA licensure of the use of product candidates, some U.S. patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Amendments. The Hatch-Waxman Amendments permit a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process. The patent term restoration period is typically one-half the time between the effective date of an IND and the submission date of a BLA, plus the time between the submission date and approval of that application. The total patent term after the extension may not exceed 14 years from the product date of product licensure. Only one patent applicable to a licensed biological product is eligible for extension and the application for the extension must be submitted prior to the expiration of the patent and within 60 days of the product’s approval. The U.S. Patent and Trademark Office, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration. Some, but not all, foreign jurisdictions possess patent term extension or other additional patent exclusivity mechanisms that may be more or less stringent and comprehensive than those of the United States. 43 Other Regulatory Matters Manufacturing, sales, promotion, and other activities of product candidates following product approval, where applicable, or commercialization are also subject to regulation by numerous regulatory authorities in the U.S. in addition to the FDA, which may include the Centers for Medicare & Medicaid Services (CMS), other divisions of the Department of Health and Human Services, the Department of Justice, the Drug Enforcement Administration, the Consumer Product Safety Commission, the Federal Trade Commission, the Occupational Safety & Health Administration, the Environmental Protection Agency, and state and local governments and governmental agencies. Numerous state, federal and foreign laws and regulations govern the collection, dissemination, use, access to, privacy and security of personal information (including health-related information). Such laws and regulations that could apply to our operations or the operations of our partners include health information privacy and security laws (HIPAA), federal and state consumer protection laws and regulations (Section 5 of the Federal Trade Commission Act), state privacy laws, data breach notification laws, and the EU General Data Protection Regulation (GDPR). In addition to regulations in the United States, we will be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our product candidate to the extent we choose to sell any products outside of the United States. Whether or not we obtain FDA approval for a product, we must obtain the requisite approvals from regulatory authorities and, if required, from independent ethics committees in foreign countries before we can commence clinical trials as well as regulatory approvals prior to marketing the product candidate in those countries. The approval processes vary from country to country and the time may be longer or shorter than that required for FDA approval. The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country. As in the United States, post approval regulatory requirements, such as those regarding product manufacture, marketing, or distribution would apply to any product that is approved outside the United States. Any drug candidates that we develop must be approved by the FDA before they may be legally marketed in the United States and by the appropriate foreign regulatory agency before they may be legally marketed in those foreign countries. Generally, our activities in other countries will be subject to regulation that is similar in nature and scope as that imposed in the United States, although there can be important differences. Additionally, some significant aspects of regulation in the European Union (EU) are addressed in a centralized way, but country-specific regulation remains essential in many respects. Healthcare and Data Privacy Regulation Federal and state healthcare laws and regulations, including fraud and abuse and health information privacy and security laws, also govern our business. These laws and regulations are constantly evolving, may conflict with each other to complicate compliance efforts, and can result in investigations, proceedings, or actions that lead to significant civil and/or criminal penalties and restrictions on data processing. Although we do not currently have any products on the market, in addition to FDA restrictions on marketing of pharmaceutical products, we are also subject to healthcare statutory and regulatory requirements and enforcement by the U.S. federal and state governments. Pharmaceutical companies and their products are subject to extensive regulation and enforcement. These laws include, without limitation: • the federal Anti-Kickback Statute, a criminal statute which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, paying, receiving or providing any remuneration (including any kickback, bribe, or certain rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid; a person or entity need not have actual knowledge of the federal Anti-Kickback Statute or specific intent to violate it in order to have committed a violation; • the federal civil and criminal false claims laws, including the civil False Claims Act (the FCA), which prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment or approval that are false, fictitious or fraudulent; knowingly making, using, or causing to be made or used, a false statement or record material to a false or fraudulent claim or obligation to pay or transmit money or property to the federal government; or knowingly concealing or knowingly and improperly avoiding or decreasing an obligation to pay money to the federal government; • manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. In addition, the government may assert that a claim that includes items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the FCA. The FCA also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the FCA and to share in any monetary recovery; 44 • the federal civil monetary penalties laws, which impose civil fines for, among other things, the offering or transfer or remuneration to a Medicare or state healthcare program beneficiary if the person knows or should know it is likely to influence the beneficiary’s selection of a particular provider, practitioner, or supplier of services reimbursable by Medicare or a state health care program, unless an exception applies; • the federal criminal statute enacted under HIPAA, which imposes criminal and civil liability for knowingly and willfully executing a scheme, or attempting to execute a scheme, to defraud any healthcare benefit program, including private payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, or falsifying, concealing or covering up a material fact or making any materially false statements in connection with the delivery of or payment for healthcare benefits, items or services. Similar to the federal Anti-Kickback Statute, a person or entity need not have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • HIPAA, as amended, and the respective implementing regulations, which imposes, among other things, specified requirements on covered entities and their business associates relating to the privacy and security of individually identifiable health information including mandatory contractual terms and required implementation of technical safeguards of such information; • the federal Physician Payments Sunshine Act, which requires manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, to monitor and report annually certain transfers of value made to U.S.-licensed physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, anesthesiologist assistants, certified nurse midwives, and U.S. teaching hospitals, as well as ownership and investment interests held by U.S.-licensed physicians and their immediate family members; and • analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third party payors, including private insurers, and may be broader in scope than their federal equivalents; state and foreign laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers; state and foreign laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers, and restrict marketing practices or require disclosure of marketing expenditures and pricing information; state and local laws that require the registration of pharmaceutical sales representatives; and state and foreign laws that govern the privacy and security of health information in some circumstances. Violations of any of these laws or any other applicable laws or regulations may result in significant penalties, including, without limitation, administrative, civil, and criminal penalties, damages, fines, disgorgement, the curtailment or restructuring of operations, integrity oversight and reporting obligations to resolve allegations of noncompliance; exclusion from participation in federal and state healthcare programs, such as Medicare and Medicaid; and imprisonment. Ensuring business arrangements comply with applicable healthcare laws, as well as responding to possible investigations by government authorities, can be time- and resource-consuming and can divert a company’s attention from its business. Coverage and Reimbursement Sales of any pharmaceutical product depend, in part, on the extent to which such product will be covered by third party payors, such as federal, state, and foreign government healthcare programs, commercial insurance and managed healthcare organizations, and the level of reimbursement for such product by third party payors. Decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a payor-by-payor basis. These third party payors are increasingly reducing coverage and reimbursement for healthcare items (including drugs) and services. Moreover, for products administered under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because of the higher prices often associated with such drugs. Additionally, separate reimbursement for the product itself may or may not be available. Instead, the hospital or administering physician may be reimbursed only for providing the treatment or procedure in which our product is used. Decreases in third party reimbursement for any drug product or a decision by a third party payor not to cover a product could reduce physician usage and patient demand for the product and also have a material adverse effect on sales. Healthcare Reform The U.S. and some foreign countries are considering proposals or have enacted legislative and regulatory changes to the healthcare system that could affect our ability to sell our products profitably. Among policy makers and payers in the U.S. and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access. 45 For example, in 2010, the U.S. enacted the ACA, which among other things, increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program; extended the Medicaid Drug Rebate program to utilization of prescriptions of individuals enrolled in Medicaid managed care organizations; subjected manufacturers to new annual fees and taxes for certain branded prescription drugs; and provided incentives to programs that increase the federal government’s comparative effectiveness research. Current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and additional downward pressure on the price for any approved products. Since the enactment of the ACA, there have been, and continue to be, numerous legal challenges and Congressional actions to repeal and replace provisions of the law. For example, with enactment of the Tax Cuts and Jobs Act of 2017 (TCJA), Congress repealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effective in 2019. Further, on June 17, 2021, the U.S. Supreme Court dismissed a judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA. Litigation and legislation over the ACA are likely to continue, with unpredictable and uncertain results. In August 2022, former President Biden signed the Inflation Reduction Act of 2022 (IRA), which introduced substantial changes to drug pricing, reimbursement and access support in the U.S., including enabling CMS to establish a “maximum fair price” for a fixed number of high expenditure pharmaceutical and biological products covered under Medicare Parts B and D following a price negotiation process with CMS (the Medicare Drug Price Negotiation Program). The IRA contains a limited exception for small biotech drug manufacturers, which applies on a drug-specific basis, and qualifying drugs will be exempt from possible pricing negotiation through 2028 and eligible for a lower limit (i.e., a price floor) on the potential maximum fair price in 2029 and 2030, if the manufacturers of those drugs continue to qualify each year (small biotech exception). Separately, in November 2023, CMS released final guidance on another program, the Medicare Part D Manufacturer Discount Program (Part D Discount Program), which will require manufacturers to take on more of the beneficiary cost previously subsidized by the federal government through the application of increased drug discounts. The IRA also imposes additional rebates for certain Part B and Part D drugs where relevant pricing metrics associated with the products increase faster than inflation. However, it is unclear how the IRA will be effectuated or changed under the new Trump Administration and the degree of impact that the IRA will ultimately have upon our business similarly remains unclear. At the state level, legislatures and regulatory agencies have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biotherapeutic product pricing, including restrictions on pricing or reimbursement at the state government level, limitations on discounts to patients, advance notices of price increases, marketing cost disclosure and transparency measures, and, in some cases, policies to encourage importation from other countries (subject to federal approval) and bulk purchasing. These laws may affect our sales, marketing, and other promotional activities by imposing administrative and compliance burdens on us. In addition, given the lack of clarity with respect to these laws and their implementation, our reporting actions could be subject to the penalty provisions of the pertinent state and federal authorities. Employees and Human Capital Management Our values of “Be Clever,” “Be of Service,” “Be Gutsy,” “Be Tenacious,” and “Be You,” are the foundation of our organization and drives our mission to improve the quality of life for patients and their families. We believe that our continued success is directly due to the commitment, engagement and performance of our employees. We strive to attract and retain experienced operators, oncology experts, clinicians, and biopharma veterans with deep market knowledge and insights with an uncompromising vision of delivering solutions for patients. In order to achieve this, we provide an inclusive and empowering work environment, foster a culture that reward performance and leadership skills, and by offering competitive compensation and benefits programs. Employees As of March 20, 2026, we had 56 full-time permanent employees. Of these employees, 80% were engaged in research and development activities and 46% had advanced degrees including Ph.D., M.D., M.B.A. and J.D. More than half of our workforce is comprised of women. None of our employees are represented by a labor union or covered by a collective bargaining agreement. We consider our relationship with our employees to be good. Culture and Employee Engagement We place a high value in the experience and expertise of our team, to foster our culture of innovation. Our employees are guided by our Code of Conduct, which sets basic requirements for business conduct and serves as a foundation for our policies, procedures and guidelines, all of which provide additional guidance on expected employee behaviors. 46 Hiring & Retention Risk We compete with biotechnology and pharmaceutical companies for qualified personnel, particularly in clinical development, regulatory affairs and technical operations. We may not be able to attract or retain personnel on acceptable terms or in a timely manner, which could affect our ability to execute our development strategy. Compensation, Benefits and Ongoing Professional Development Drug development is a complex endeavor which requires deep expertise and experience across a broad array of disciplines. Biotechnology and pharmaceutical companies both large and small compete for a limited number of qualified applicants to fill specialized positions. As part of our total rewards philosophy, we offer competitive compensation and benefits to attract and retain top talent. We are committed to fair and equitable treatment in our compensation and benefits for employees at all levels. We provide our employees with compensation packages that include competitive base salaries, incentive bonuses, and new hire and long-term incentive equity awards. We believe that providing employees with the opportunity to earn ownership interest in the company encourages employees to act in our long-term best interests, aligns the interests of our stockholders with our employees, and further strengthens the level of employee engagement. Employees can also participate in our Employee Share Purchase Plan (ESPP) which provides our employees with an opportunity to purchase shares of our common stock at a discount. Our total rewards offerings also include an array of programs to support our employees' financial well-being, including retirement savings programs with matching contributions for eligible employees, health and welfare benefits, and paid time off. We have also created a flexible work policy to allow our employees to work remotely. For our facility-dependent employees, including those needed to maintain our research and development activities, we implemented comprehensive safety protocols designed to ensure a healthy environment. We also provide reimbursement and time for employees to attend professional development courses ranging from technical training, competency-based workshops, and leadership development programs. Direct managers also take an active role in identifying individualized development plans to assist their employees in realizing their full potential and creating opportunities for promotions and added responsibilities that enhance the engagement and retention of our workforce. We are committed to maintaining and increasing our investment in our workforce as we grow, including improvements in the way we hire, develop, motivate and retain employees. Board of Directors Oversight Our Board of Directors (the Board) recognizes the critical importance of our team and innovative work environment that is centered around a values-based culture. Our Board meets regularly with management to discuss issues impacting our employees, and to focus on ways to support our workforce. Our focus on culture comes from our Board and flows throughout our company. In evaluating our Chief Executive Officer and management team, significant emphasis is placed on their contributions to our overall culture. Our Board’s Compensation Committee is responsible for reviewing with management our human resources activities, which include, among other things, matters relating to employee development, management and engagement, pay equity, and our demographics. Our Board’s Nominating and Corporate Governance Committee is responsible for developing and recommending to the Board any company program relating to corporate responsibility and sustainability, including environmental, social and governance matters. The Board receives periodic updates regarding workforce planning and organizational capability. Corporate Information We were incorporated in the state of Delaware on June 11, 2018, and launched with our first employee and Series A funding in July 2019. Our principal executive offices are located at 321 Harrison Avenue, Boston, MA 02118, and our telephone number is (617) 453-3596. Our website address is www.pyxisoncology.com. Our common stock is listed on The Nasdaq Global Market under the ticker symbol “PYXS.” The information in, or that can be accessed through, our website is not a part of this Annual Report on Form 10-K. Our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and amendments to those reports filed or furnished pursuant to Section 12(a) or 15(d) of the Exchange Act are available, free of charge, on or through our website as soon as reasonably practicable after such reports and amendments are electronically filed with or furnished to the U.S. Securities and Exchange Commission (SEC). The SEC maintains an Internet site that contains, reports, proxy and information statements and other information regarding our filings at sec.gov. The contents of these websites are not incorporated into this filing. Further, references to the URLs for these websites are intended to be inactive textual references only. 47 Item 1A. Ris k Factors. Our business involves a high degree of risk. You should consider and read carefully all of the risks and uncertainties described below, as well as other information included in this Annual Report on Form 10-K, including our financial statements and related notes appearing at the end of this Annual Report on Form 10-K. The risks described below are not the only ones facing us. The occurrence of any of the following risks or additional risks and uncertainties not presently known to us or that we currently believe to be immaterial could materially and adversely affect our business, financial condition or results of operations. In such case, the trading price of our common stock could decline, and you may lose all or part of your investment. This Annual Report on Form 10-K also contains forward-looking statements and estimates that involve risks and uncertainties. Our actual results could differ materially from those anticipated in the forward-looking statements as a result of specific factors, including the risks and uncertainties described below. Risks Related to Our Financial Position and Need for Additional Capital We are a clinical stage oncology company with a limited operating history and have incurred significant losses since our inception and anticipate that we will continue to incur losses over at least the next several years and may never achieve or maintain profitability. Since our inception, we have incurred significant operating losses. We reported net losses of $79.6 million and $77.3 million for the years ended December 31, 2025 and 2024, respectively. As of December 31, 2025, we had an accumulated deficit of $443.2 million. To date, we have not generated any revenues from product sales and have financed our operations primarily through equity offerings. As such, we expect that it will be several years, if ever, before we have a product candidate ready for regulatory licensure and commercialization. We may never succeed in these activities and, even if we do, may never generate revenues that are significant enough to achieve profitability. To become and remain profitable, we must succeed in developing, obtaining marketing licensure for and commercializing products that generate significant revenue. This will require us to be successful in a range of challenging activities, including, without limitation, procuring clinical- and commercial-scale manufacturing, successfully completing preclinical studies and clinical trials of our product candidate, establishing arrangements with third parties for the conduct of our clinical trials, obtaining marketing licensure for our product candidate, manufacturing, marketing and selling any products for which we may obtain marketing licensure, discovering or obtaining rights to additional product candidates, identifying collaborators to develop product candidates we identify or additional uses of our existing product candidate and successfully completing development of our product candidate for our collaboration partners. We expect to continue to incur significant expenses and increasing operating losses for at least the next several years. We anticipate that our expenses will increase substantially if and as we: • continue to develop, conduct clinical trials and seek regulatory approvals for MICVO; • scale up external manufacturing capabilities for later stage trials and to commercialize our products; • expand, maintain and protect our intellectual property portfolio; • ultimately establish a sales, marketing and distribution infrastructure for which we may obtain marketing licensure; • hire additional clinical, regulatory, scientific, operational, financial and management information personnel; and • continue to operate as a public company. Our expenses could increase beyond our expectations if we are required by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) or other comparable regulatory authorities to perform trials in addition to those that we currently expect to perform, or if we experience any delays in establishing appropriate manufacturing arrangements for completing our clinical trials or the clinical development of our product candidate. Because of the numerous risks and uncertainties associated with pharmaceutical product development, we are unable to accurately predict the timing or amount of increased expenses we will incur or when, if ever, we will be able to achieve profitability. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable would depress the value of our company and could impair our ability to raise capital, expand our business, maintain our research and development efforts or continue operations. A decline in the value of our company, or in the value of our common stock, could also cause investors to lose all or part of their investment. Even if we are able to generate revenues from the sale or out-licensing of any approved products, we may not become profitable and may need to obtain additional funding to continue operations. 48 We have substantial doubt about our ability to continue as a going concern and we will require substantial additional capital to finance our operations. If we are unable to raise such capital when needed, or on acceptable terms, we may not be able to continue as a going concern or we may be forced to delay, reduce or eliminate one or more of our research and product development programs or future commercialization efforts. Our recurring losses from operations raise substantial doubt about our ability to continue as a going concern. As a result, the financial statements accompanying this Annual Report on Form 10-K include a statement that there is substantial doubt about our ability to continue as a going concern for one year after the date the financial statements were issued, and these financial statements do not include any adjustments that might result from the outcome of this uncertainty. The development of biopharmaceutical products, including conducting preclinical studies and clinical trials, is a very time-consuming, expensive and uncertain process that takes years to complete. Our operations have consumed substantial amounts of cash since inception, and we expect our expenses to increase in connection with our ongoing and planned activities, particularly as we continue our clinical trials for MICVO. As of December 31, 2025, we had approximately $68.3 million in cash, cash equivalents, restricted cash and marketable debt securities. We believe that our cash, cash equivalents and marketable debt securities as of December 31, 2025, will be sufficient to fund our operations into the fourth quarter of 2026. However, we have based this estimate on assumptions that may prove to be wrong, and our operating plan may change as a result of many factors currently unknown to us. In addition, we could utilize our available capital resources sooner than we expect. Even if our product candidate is approved for commercial sale, we anticipate incurring significant costs associated with sales, marketing, manufacturing and distribution activities. Our expenses could increase beyond expectations if we are required by the FDA, the EMA or other comparable regulatory authorities to perform clinical trials or preclinical studies in addition to those that we currently anticipate. Other unanticipated costs may also arise. Because the design and outcome of our planned and anticipated clinical trials are highly uncertain, we cannot reasonably estimate the actual amount of resources and funding that will be necessary to successfully complete the development and commercialization of any product candidate we develop. Accordingly, we will need to obtain substantial additional funding in order to continue our operations. Our estimate as to how long we expect to be able to continue to fund our operations is based on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we currently expect. Changing circumstances, some of which may be beyond our control, including market volatility resulting from global economic developments, political unrest, high inflation and other factors, could cause us to consume capital significantly faster than we currently anticipate, and we may need to seek additional funds sooner than planned. We intend to use our cash and cash equivalents for development and regulatory activities relating to our product candidate, and other general corporate purposes. Advancing the development of our product candidate will require a significant amount of capital. Our cash and cash equivalents will not be sufficient to fund our product candidate through regulatory licensure. Because the length of time and activities associated with successful research and development of any individual product candidate are highly uncertain, we are unable to estimate the actual funds we will require for development, marketing licensure and commercialization activities. The timing and amount of our operating expenditures will depend largely on: • the cost associated with dose escalation and dose expansion mono and combo clinical trials for our product candidate; • the manufacture of drug products and drug substance for our product candidate; • the timing and progress of our other preclinical and clinical development activities; • the costs and timing of future commercialization activities, including product manufacturing, marketing, sales and distribution, for our product candidate for which we receive marketing licensure; • our ability to maintain our current licenses and research and development programs and to establish new collaboration arrangements; • the costs involved in prosecuting, maintaining, enforcing and expanding patent and other intellectual property rights; • the cost and timing of regulatory licenses; and • insurance, legal and other regulatory compliance expenses to operate as a public company. 49 If we are unable to obtain funding on a timely basis or on acceptable terms, we may not be able to continue as a going concern, we may have to delay, reduce or terminate our clinical trials, limit strategic opportunities or undergo reductions in our workforce or other corporate restructuring activities. We also could be required to seek funds through arrangements with collaborators or others that may require us to relinquish rights to some of our technologies or our product candidate that we would otherwise pursue on our own. We will be required to seek additional funding in the future and our ability to raise additional funds will depend on financial, economic and other factors, many of which are beyond our control. Additional funds may not be available to us on acceptable terms or at all. For example, market volatility resulting from global economic developments, political unrest, high inflation and other factors could adversely impact our ability to access capital as and when needed. If we raise additional funds by issuing equity securities, our stockholders will suffer dilution and the terms of any financing may adversely affect the rights of our stockholders. In addition, as a condition to providing additional funds to us, future investors may demand, and may be granted, rights superior to those of existing stockholders. Adverse developments affecting the financial services industry, including events or concerns involving liquidity, defaults or non-performance by financial institutions or transactional counterparties, could adversely affect our business, financial condition or results of operations. Events involving limited liquidity, defaults, non-performance or other adverse developments that affect financial institutions, transactional counterparties or other companies in the financial services industry or the financial services industry generally, or concerns or rumors about any events of these kinds or other similar risks, have in the past and may in the future lead to market-wide liquidity problems. Although we assess our banking and customer relationships as we believe necessary or appropriate, our access to funding sources and other credit arrangements in amounts adequate to finance or capitalize our current and projected future business operations could be significantly impaired by factors that affect us, the financial services industry or economy in general. These factors could include, among others, events such as liquidity constraints or failures, the ability to perform obligations under various types of financial, credit or liquidity agreements or arrangements, disruptions or instability in the financial services industry or financial markets, or concerns or negative expectations about the prospects for companies in the financial services industry. In addition, investor concerns regarding the U.S. or international financial systems could result in less favorable commercial financing terms, including higher interest rates or costs and tighter financial and operating covenants, or systemic limitations on access to credit and liquidity sources, thereby making it more difficult for us to acquire financing on acceptable terms or at all. Any decline in available funding or access to our cash and liquidity resources could, among other risks, adversely impact our ability to meet our operating expenses, financial obligations or fulfill our other obligations, result in breaches of our contractual obligations or result in violations of federal or state wage and hour laws. Any of these impacts, or any other impacts resulting from the factors described above or other related or similar factors not described above, could have material adverse impacts on our liquidity and our business, financial condition or results of operations. In addition, changes in global macroeconomic conditions and government trade policies could further increase our operating costs and accelerate our need for additional capital. New or increased tariffs, trade restrictions, retaliatory measures, or other limitations on the movement of goods and services, whether imposed by the United States or other jurisdictions, could increase the cost of materials, equipment and services used in our research, development and manufacturing activities. Such measures could also disrupt global supply chains, increase transportation and logistics costs, and create delays in the delivery of clinical supplies. Any of these developments could materially increase our cash burn, delay development timelines, and adversely affect our ability to obtain additional financing on acceptable terms, or at all. Risks Related to the Development of our Product Candidate Clinical testing and product development is a lengthy and expensive process with an uncertain outcome. We may incur unexpected costs or experience delays in completing, or ultimately be unable to complete, the clinical testing and the development and commercialization of our product candidate. Before obtaining marketing approval from regulatory authorities for the sale of our product candidate, we or our collaborators must conduct extensive trials to demonstrate the safety and efficacy of the product candidate. Clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to the timing and outcome. A failure of one or more clinical trials can occur at any stage of the process. We may experience numerous unforeseen events during, or as a result of, clinical trials, which could delay or prevent our ability to receive marketing licensure or commercialize our product candidate, including: • delays in reaching, or the failure to reach, a consensus with regulators on clinical trial design; • the supply or quality of our product candidate or other materials necessary to conduct clinical trials of our product candidate may be insufficient or inadequate, including as a result of delays in the testing, validation, manufacturing and delivery of product candidate to the clinical sites by us or by third parties with whom we have contracted to perform certain of those functions; • delays in reaching, or the failure to reach, agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites; 50 • the failure of regulators or institutional review boards to authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site; • difficulty in designing clinical trials and in selecting endpoints for diseases that have not been well studied and for which the natural history and course of the disease is poorly understood; • the selection of certain clinical endpoints that may require prolonged periods of clinical observation or analysis of the resulting data; • we may receive feedback from regulatory authorities that requires us to modify the design of our clinical trials; • the number of patients required for clinical trials of our product candidate may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate, participants may fail during screening or drop out of these clinical trials at a higher rate than we anticipate or fail to return for post-treatment follow-up or the failure to recruit suitable patients to participate in our clinical trials; • our product candidate may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators or institutional review boards to suspend or terminate our clinical trials; • we may have to suspend or terminate clinical trials of our product candidate for various reasons, including a finding that the participants are being exposed to unacceptable safety risks or that the benefit-risk ratio is negative; • the third parties with whom we contract may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; • the requirement from regulators or institutional review boards that we or our investigators suspend or terminate clinical trials for various reasons, including noncompliance with regulatory requirements or unacceptable safety risks; • clinical trials of our product candidate may produce negative or inconclusive results and we may decide, or regulators may require us, to conduct additional clinical trials or abandon product candidate development and discovery programs; • the cost of clinical trials of our product candidate may be greater than we anticipate; • imposition of a clinical hold by regulatory authorities as a result of a serious adverse event, concerns with the class of our product candidate or after an inspection of our clinical trial operations, trial sites or manufacturing facilities; • occurrence of serious adverse events associated with the product candidate that are viewed to outweigh its potential benefits; • regulators may revise the requirements for approving our product candidate, or such requirements may not be as we anticipate; and • delays in developing and validating any companion diagnostic to be used in the trial, to the extent we are required to do so. The FDA may modify or enhance clinical trial requirements which may affect enrollment and retention of patients and may increase costs and delay clinical programs. If we are required to conduct additional clinical trials or other testing of our product candidate beyond those that we currently contemplate, if we are unable to successfully complete clinical trials of our product candidate or other testing, if the results of these trials or tests are not positive or are only modestly positive or if there are safety concerns, we may: • be delayed in obtaining marketing licensure for our product candidate; • not obtain marketing licensure at all; • obtain licensure for indications or patient populations that are not as broad as intended or desired; • obtain licensure with labeling that includes significant use or distribution restrictions or safety warnings; • be required to perform additional clinical trials to support marketing licensure; • have regulatory authorities withdraw or suspend their license, or impose restrictions on distribution of the product candidate in the form of a modified REMS; • be subject to additional post-marketing testing requirements or changes in the way the product is administered; • fail to receive approval of any companion diagnostics that may be required by the FDA or comparable foreign regulatory authorities in connection with approval of our therapeutic product candidate; or • have our product removed from the market after obtaining marketing licensure. 51 Our product development costs also will increase if we experience delays in preclinical studies or clinical trials or in obtaining marketing licensure. We do not know whether any of our preclinical studies or clinical trials will need to be restructured or will be completed on schedule, or at all. Significant preclinical study or clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our product candidate, or could allow our competitors to bring products to market before we do and impair our ability to successfully commercialize our product candidate, which may harm our business, results of operations, financial condition and prospects. Further, cancer therapies sometimes are characterized as first line, second line or third line. The FDA often approves or licenses new oncology therapies initially only for third line or later use, meaning for use after two or more other treatments have failed. When cancer is detected early enough, first line therapy, usually hormone therapy, surgery, radiation therapy, immunotherapy or a combination of these, is sometimes adequate to cure the cancer or prolong life without a cure. Second line and third line therapies are administered to patients when prior therapy is not effective. Our clinical trials are, and any future clinical trials will be, with patients with difficult to treat cancer. We expect that we would initially seek regulatory licensure for use of this product candidate in appropriate treatment settings. Subsequently, for those products that prove to be sufficiently beneficial, if any, we would expect to seek licensure potentially as a first line therapy, but any product candidate we develop, even if approved for second line or third line therapy, may not be approved for first line therapy and, prior to seeking and/or receiving any licensures for first line therapy, we may have to conduct additional clinical trials. We are heavily dependent on the success of our product candidate, MICVO, which is in the early stages of clinical development. If MICVO is not successful in clinical trials or does not receive regulatory approval or licensure or is not successfully commercialized, our business will be materially and adversely affected. To date, we have invested a significant portion of our efforts and financial resources in the development of MICVO. Our future success is substantially dependent on our ability to successfully initiate and complete clinical development for, obtain regulatory licensure for, and successfully commercialize MICVO, which may never occur. We currently have no products that are approved or licensed for commercial sale and may never be able to develop a marketable product. We expect that a substantial portion of our efforts and expenditures over the next few years will be devoted to the clinical development, management of clinical and manufacturing activities, regulatory licensure, establishing commercial scale manufacturing, and significant sales, marketing, and distribution efforts related to MICVO before we can generate any revenues from any commercial sales. We cannot be certain that we will be able to successfully complete any of these activities or that, even if MICVO receives regulatory licensure, such product will be able to successfully compete against therapies and technologies offered by other companies. The research, testing, manufacturing, labeling, licensure, sale, packaging, marketing, and distribution of biological products are subject to extensive regulation by the FDA and comparable regulatory authorities in other countries. We are not permitted to market MICVO in the U.S. until we receive licensure of a BLA or NDA from the FDA for such product candidate, as appropriate. Further, we are not permitted to market MICVO in any foreign countries until we receive the requisite licensure or approvals from such countries. We have not submitted a BLA or NDA to the FDA or comparable applications to any other comparable regulatory authorities for MICVO. We will not be in a position to do so for several years, if ever. If we are unable to obtain the necessary regulatory licensure or approvals for MICVO, our financial position will be materially adversely affected, and we may not be able to generate sufficient revenues to continue our business. Evolving regulatory expectations for oncology drug development could require additional studies and delay or prevent approval of our product candidate. Regulatory expectations for oncology drug development continue to evolve. In recent years, regulatory authorities, including the U.S. Food and Drug Administration, have placed increased emphasis on dose optimization and dose selection to balance efficacy and safety. These evolving expectations may require additional dose-ranging studies, expanded clinical trial designs, or generation of additional data beyond what we currently anticipate. If regulatory authorities impose additional requirements on our development program, we may incur substantial additional expense, experience delays in enrollment or completion of clinical trials, or be required to modify our development plans. Any of these outcomes could delay or prevent regulatory approval and materially adversely affect our business and prospects. 52 Our product candidate may fail in development or suffer delays that materially and adversely affect its commercial viability. If we or our existing or future collaborators are unable to initiate and complete clinical development of, obtain regulatory approval or licensure for or commercialize our product candidate or experience significant delays in doing so, our business will be materially harmed. Our ability to achieve and sustain profitability depends on obtaining regulatory licensure for and successfully commercializing our product candidate, either alone or with third parties. Before obtaining regulatory licensure for the commercial distribution of our product candidate, we or an existing or future collaborator must conduct extensive preclinical studies and clinical trials to demonstrate the safety, purity and potency in humans of our product candidate. We may not have the financial resources to continue development of, or to modify existing or enter into new collaborations for, a product candidate if we experience any issues that delay or prevent regulatory licensure of, or our ability to commercialize, a product candidate, including: • negative or inconclusive results from preclinical studies or clinical trials leading to a decision or requirement to conduct additional preclinical studies or clinical trials or abandon a program; • product-related side effects experienced by participants in our clinical trials or by individuals using therapeutic biological products similar to our product candidate; • failure in obtaining the necessary approvals from regulators to commence a clinical trial, or a suspension or termination of a clinical trial once commenced; • conditions imposed by the FDA, the EMA or other comparable authorities regarding the scope or design of our clinical trials; • delays in enrolling patients in clinical trials; • high drop-out rates of patients; • inadequate supply or quality of product candidate components or materials or other supplies necessary for the conduct of our clinical trials; • greater than anticipated clinical trial costs; • poor effectiveness of our product candidate during clinical trials; • unfavorable FDA or other comparable regulatory agency inspection and review of a clinical trial site; • failure of our third party contractors or investigators to comply with regulatory requirements or otherwise meet their contractual obligations in a timely manner, or at all; • delays and changes in regulatory requirements, policy and guidelines, including the imposition of additional regulatory oversight around clinical testing generally or with respect to our technology in particular; • varying interpretations of data by the FDA, the EMA and other comparable foreign regulatory authorities; or • landscape changes around market access and pricing policies that may impact reimbursement and product sales. If any of the foregoing circumstances occur, we could experience significant delays or an inability to successfully commercialize our product candidate, which could materially harm our business. Moreover, if we do not receive regulatory approvals, we may not be able to continue our operations. 53 We have no experience as a company completing a clinical trial or submitting a BLA or NDA and may be unable to successfully do so for MICVO. The conduct of a clinical trial is a long, expensive, complicated and highly regulated process. Although certain of our employees have conducted successful clinical trials and made regulatory submissions in the past across many therapeutic areas while employed at other companies, we, as a company, have not completed any clinical trials, or submitted a BLA or NDA, and as a result may require more time and incur greater costs than we anticipate. Failure to commence or complete, or delays in, our clinical trials or planned regulatory submissions would prevent us from, or delay us in, obtaining regulatory approval of and commercializing MICVO, which would adversely impact our financial performance. Large-scale clinical trials would require significant additional financial and management resources and heavier reliance on third party clinical research organizations (CROs) and consultants. Relying on third party CROs and consultants may cause us to encounter delays or other operational issues that are outside of our control. Although our third parties are required to comply with good laboratory practice (GLP) and good clinical practice (GCP) for any studies or trials we plan to submit to a regulatory authority, and have historically complied, relying on third parties in the conduct of our preclinical studies or clinical trials exposes us to a risk that they may not adequately comply with GLP or GCP in the future. We may be unable to identify and contract with sufficient investigators, CROs and consultants on terms that are acceptable to us on a timely basis or at all. We may not be able to submit INDs to commence additional clinical trials on the timelines we expect and, even if we are able to, the FDA may not permit us to proceed. We may submit additional INDs in the future. We may experience manufacturing delays or other delays with IND-enabling studies. Moreover, we cannot be sure that submission of an IND will result in the FDA allowing us to commence clinical trials or that, once begun, issues will not arise that lead to the suspension or termination of our clinical trials. Additionally, even if the applicable regulatory authorities agree with the design and implementation of the clinical trials set forth in our INDs, we cannot guarantee that those regulatory authorities will not change their requirements in the future, or that circumstances will not arise under which FDA or other regulatory authorities may place our clinical trials on partial or full clinical hold. These considerations apply to the INDs described above and also to new clinical trials we may submit as amendments to existing INDs or as part of new INDs in the future. Any failure to submit INDs on the timelines we expect or to obtain authorization to proceed with our trials may prevent us from completing our clinical trials or commercializing our products on a timely basis, if at all. Our preclinical studies and clinical trials may fail to demonstrate adequately the safety, purity and potency of our product candidate, which would prevent or delay development, regulatory approval or licensure and commercialization. Before obtaining regulatory licensure for the commercial sale of our product candidate we must demonstrate through lengthy, complex and expensive preclinical studies and clinical trials that our product candidate is safe, pure, and potent, as required under a BLA. Preclinical and clinical testing is expensive and can take many years to complete and the outcome of these activities is inherently uncertain. Failure can occur at any time during the preclinical studies and clinical trial processes and, because our product candidate is in an early stage of development, there is a high risk of failure. In addition, any failures or adverse outcomes in preclinical or clinical testing seen by other developers of a similar product candidate could materially impact the success of our program. We may never succeed in developing marketable products. It is also possible that the results of preclinical studies and early clinical trials of our product candidate may not be predictive of the results of later-stage clinical trials. Although our product candidate may demonstrate promising results in preclinical studies and early clinical trials, it may not prove to be effective in subsequent clinical trials. For example, testing on animals occurs under different conditions than testing in humans and, therefore, the results of animal studies may not accurately predict human experience. There is typically an extremely high rate of attrition from the failure of a product candidate proceeding through preclinical studies and clinical trials. A product candidate in later stages of clinical trials may fail to show the desired safety, purity, and potency profile despite having progressed successfully through preclinical studies and/or initial clinical trials. Likewise, early, smaller-scale clinical trials may not be predictive of eventual safety, purity and potency in large-scale pivotal clinical trials. Many companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of potency, insufficient durability of potency or unacceptable safety issues, notwithstanding promising results in earlier trials. Most product candidates that commence preclinical studies and clinical trials are never approved or licensed for commercialization. In addition, preclinical studies or clinical trials we conduct may contradict, undermine or otherwise not replicate or advance the results of the research programs and preclinical studies that were completed prior to our in-licensing or acquisition of our product candidate, which may materially and adversely affect our business, results of operations and prospects. 54 Additionally, our PYX-201-101 Phase 1 clinical trial is an open label study, where both the patient and investigator know whether the patient is receiving the investigational product candidate. Most typically, open label clinical trials test only the investigational product candidate and sometimes do so at different dose levels. Open-label clinical trials are subject to various limitations that may exaggerate any therapeutic effect as patients in open label clinical trials are aware when they are receiving treatment. In addition, open label clinical trials may be subject to an “investigator bias” where those assessing and reviewing the physiological outcomes of the clinical trials are aware of which patients have received treatment and may interpret the information of the treated group more favorably given this knowledge. For instance, the FDA may also not consider open label clinical trials to be adequate and well controlled trials sufficient to support BLA licensure. Any preclinical studies or clinical trials that we may conduct may not demonstrate the safety, purity, and potency necessary to obtain regulatory licensure to market our product candidate. If the results of our ongoing or future preclinical studies and clinical trials are inconclusive with respect to the safety, purity, and potency of our product candidate, if we do not meet the clinical endpoints with statistical and clinically meaningful significance or if there are safety concerns associated with our product candidate, we may be prevented or delayed in obtaining marketing licensure for the product candidate. In some instances, there can be significant variability in safety, purity, and potency results between different preclinical studies and clinical trials of the same product candidate due to numerous factors, including changes in trial procedures set forth in protocols, differences in the size and type of the patient populations, changes in and adherence to the clinical trial protocols and the rate of dropout among clinical trial participants. Results of our trials could reveal a high and unacceptable severity and prevalence of these or other side effects. If that were to occur, or if other developers of similar products were to find an unacceptable severity or prevalence of side effects with their candidates, our trials could be suspended or terminated, and the FDA or comparable foreign regulatory authorities could order us to cease further development of or deny licensure of our product candidate for any or all targeted indications. Product-related side effects could also affect patient recruitment or the ability of enrolled patients to complete an ongoing trial or result in potential product liability claims. Any of these occurrences may significantly harm our business, financial condition and prospects. Further, our product candidate could cause undesirable side effects in clinical trials related to on-target toxicity. If an unacceptable safety profile is observed or if our product candidate has characteristics that are unexpected, we may need to abandon its development or limit development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective. Many compounds that initially showed promise in early stage testing for treating cancer have later been found to cause side effects that prevented further development of the compound. Interim top-line and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes to the final data. From time to time, we may publish interim top-line or preliminary data from our clinical trials. For example, in December 2025, we announced preliminary data from our dose expansion phase of Phase 1 clinical trial of MICVO. Preliminary data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available. Preliminary or top-line data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. Preliminary or top-line data may include, for example, data regarding a small percentage of the patients enrolled in a clinical trial, and such preliminary data should not be viewed as an indication, belief or guarantee that other patients enrolled in such clinical trial will achieve similar results or that the preliminary results from such patients will be maintained. As a result, interim and preliminary data should be viewed with caution until the final data is available. Differences between preliminary or interim data and final data could significantly harm our business prospects and may cause the trading price of our common stock to fluctuate significantly. We are parties to and may in the future enter into additional agreements with third parties under which those parties have or will be granted a license to develop product candidates discovered using our APXiMAB Platform. If any such programs are not successful or if disputes arise related to such programs, we may not realize the full commercial benefits from such programs. Our APXiMAB Platform has enabled the discovery of several product candidates with potential utility in multiple therapeutic areas and has resulted in several programs that have been licensed to third parties, including larger global biopharmaceutical companies and mid-sized regional or China-focused companies. Such arrangements generally allow the licensing parties to control the amount and timing of resources that they dedicate to the development or potential commercialization of any product candidates they develop from the technology we have licensed to them, subject to any territorial or field of use restrictions in the license. Apexigen typically negotiated milestone payments and royalty fees from the licensees that will require various levels of success with their product candidate development program in order for us to generate revenue from them. Our ability to generate revenue from these licensing arrangements will depend on our counterparties’ abilities to successfully develop and commercialize the product candidates they are developing. We cannot predict the success of any licensing program that we enter into or whether such program will lead to any meaningful milestone or royalty revenue to us. 55 We may expend our resources to pursue a particular product candidate and fail to capitalize on product candidates that may be more profitable or for which there is a greater likelihood of success. As a result of our limited financial and managerial resources, we must make strategic decisions as to which targets and product candidate to pursue and may forego or delay pursuit of opportunities with other targets or product candidates or for other indications that later prove to have greater commercial potential. Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities. Failure to properly assess a potential product candidate could result in our focus on a product candidate with low market potential, which would harm our business, financial condition, results of operations and prospects. Our spending on current and future research, our product candidate and discovery programs for specific targets or indications may not yield any commercially viable products. If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidate. The market may not be receptive to MICVO because it is based on our novel therapeutic modality, and we may not generate any future revenue from the sale or licensing of this product candidate. Even if regulatory licensure is obtained for our product candidate, we may not gain sufficient market acceptance among physicians, patients, healthcare payors and others in the medical community. MICVO is based on the FACT Platform. Our future success depends on the successful development of this novel therapeutic approach. Additionally, the regulatory licensure process for a novel product candidate such as ours can be more expensive and take longer than for other, better-known or extensively-studied product candidates. No regulatory authority has granted licensure for any therapeutic using the FACT Platform. As a result of these factors, it is more difficult for us to predict the time and cost of product candidate development. Any development problems we experience in the future related to our program may cause significant delays or unanticipated costs or may prevent the development of a commercially viable product. Advancing our products creates significant challenges for us, including educating medical personnel regarding the potential potency and safety benefits, as well as the challenges, of incorporating our product candidate, if approved, into treatment regimens and establishing the sales and marketing capabilities to gain market acceptance, if approved. Any of these factors may prevent us from commercializing our product candidate we may develop on a timely or profitable basis, if at all. Market acceptance of our product candidate will depend on, among other factors: • the timing of our receipt of any marketing and commercialization licensures; • the terms of any licensures and the countries in which licensures are obtained; • the safety, purity, and potency of our product candidate; • the prevalence and severity of any adverse side effects associated with our product candidate; • the limitations or warnings contained in any labeling approved by the FDA, or other comparable foreign regulatory authorities; • the relative convenience and ease of administration of our product candidate; • the willingness of patients to accept any new methods of administration; • the success of our physician education programs; • the availability of adequate government and third party payor reimbursement; • the pricing of our products, particularly as compared to alternative treatments; and • the availability of alternative effective treatments for the disease indications our product candidate is intended to treat and the relative risks, benefits and costs of those treatments. If any product candidate we commercialize fails to achieve market acceptance, it could have a material and adverse effect on our business, financial condition, results of operations and prospects. 56 We are early in our development efforts. Our lead product candidate, MICVO, is in the early stages of clinical development. The results of preclinical studies and early stage clinical trials may not be predictive of future results in later studies or trials. Initial success in clinical trials may not be indicative of results obtained when these trials are completed or in later-stage clinical trials. The results of preclinical studies may not be predictive of the results of clinical trials, and the results of any early stage clinical trials that are continuing may not be predictive of the results of the later stage clinical trials. In addition, initial success in clinical trials may not be indicative of results obtained when such trials are completed on in later stage clinical trials. In particular, the small number of patients in our Phase 1 clinical trial may make the result of this trial less predictive of the outcome of later clinical trials. Moreover, preclinical and clinical data often are susceptible to varying interpretations and analyses, and many companies that have believed their product candidate performed satisfactorily in preclinical studies and clinical trials nonetheless have failed to obtain marketing licensure of their products. Our clinical trials may not ultimately be successful or support further clinical development of MICVO. There is a high failure rate for a product candidate proceeding through clinical trials. Many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in clinical development even after achieving encouraging results in earlier studies. Any such setbacks in our clinical development could materially harm our business, results of operations, financial condition and prospects. If we or our collaborators experience delays or difficulties in the enrollment of patients in our clinical trials, these clinical trials could be delayed or prevented. We may not be able to continue clinical trials for our product candidate if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials, as required by the FDA or other comparable foreign regulatory authorities. Our ability to identify sites who will enroll eligible patients for clinical trials may turn out to be limited or we may be slower in enrolling these trials than we anticipate. In addition, some of our competitors have ongoing clinical trials for product candidates that treat the same indications as our product candidate and, as a result, patients who would otherwise be eligible for our clinical trials may instead elect to enroll in clinical trials of our competitors’ product candidates. Patient enrollment in clinical trials is also affected by other factors including: • the severity of the disease under investigation; • the size and nature of the patient population; • the eligibility criteria for the trial in question; • the competing clinical trials or approved therapies which present an attractive alternative to patients and their physicians; • the perceived risks and benefits of the product candidate under study, including as a result of adverse effects observed in similar or competing therapies; • the efforts to facilitate timely enrollment in clinical trials; • the patient referral practices of physicians; • the burden on patients due to the scope and invasiveness of required procedures under clinical trial protocols, some of which may be inconvenient and/or uncomfortable; • the ability to monitor patients adequately during and after treatment; • the proximity and availability of clinical trial sites for prospective patients; • the risk that a high number of patients fail during screening or enrolled patients will drop out or die before completion of the trial; • patients failing to complete a clinical trial or returning for post-treatment follow-up; and • our ability to manufacture the requisite materials for a patient and clinical trial. Our or our collaborators inability to timely enroll a sufficient number of patients for our clinical trials, based on the above factors or others, could result in significant delays and could require us to abandon one or more clinical trials altogether. Enrollment delays in our clinical trials may result in increased development costs for our product candidate, which would cause the value of our company to decline and limit our ability to obtain additional financing. 57 Our product candidate may cause undesirable and unforeseen side effects or have other properties impacting safety that could halt its clinical development, delay or prevent its regulatory licensure, limit its commercial potential or result in significant negative consequences. Undesirable side effects caused by our product candidate could cause regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory licensure or approval by the FDA or other regulatory authorities. As is the case with oncology drugs, it is likely that there may be side effects associated with their use. Results of our trials could reveal a high and unacceptable severity and prevalence of these or other side effects. In such an event, our trials could be suspended or terminated, and the FDA or comparable foreign regulatory authorities could order us to cease further development of or deny licensure or approval of our product candidate for any or all targeted indications. Such side effects could also affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Any of these occurrences may materially and adversely affect our business, financial condition, results of operations and prospects. Further, clinical trials by their nature utilize a sample of the potential patient population. With a limited number of patients and limited duration of exposure, rare and severe side effects of our product candidate may only be uncovered with a significantly larger number of patients exposed to the product candidate. In the event that our product candidate receives regulatory licensure or approval and we or others later identify undesirable side effects, any of the following adverse events could occur, which could result in significant negative consequences: • regulatory authorities may withdraw their licensure or approval of the product or seize the product; • we may be required to recall the product or change the way the product is administered to patients; • additional restrictions may be imposed on the marketing of the particular product or the manufacturing processes for the product or any component thereof; • we may be subject to fines, injunctions or the imposition of civil or criminal penalties; • regulatory authorities may require the addition of labeling statements, such as a “black box” warning or a contraindication; • we may be required to create a medication guide outlining the risks of such side effects for distribution to patients; • we could be sued and held liable for harm caused to patients; • the product may become less competitive; and • our reputation may suffer. If we do not achieve our projected development goals in the timeframes we announce and expect, the commercialization of our products may be delayed and, as a result, our stock price may decline. From time to time, we estimate the timing of the anticipated accomplishment of various scientific, clinical, regulatory and other product development goals, which we sometimes refer to as milestones. These milestones may include the commencement or completion of preclinical studies and clinical trials and the submission of regulatory filings and may be associated with payments from collaborators. From time to time, we may publicly announce the expected timing of some of these milestones. All of these milestones are and will be based on numerous assumptions. The actual timing of these milestones may vary dramatically compared to our estimates, in some cases for reasons beyond our control. If we do not meet these milestones as publicly announced, or at all, our revenue may be lower than expected, the commercialization of our products may be delayed or never achieved and, as a result, our stock price may decline. We may face significant competition from other oncology-focused biotechnology and pharmaceutical entities, and our operating results will suffer if we fail to compete effectively. The development and commercialization of therapeutic biological products is highly competitive. We compete with a variety of multinational biopharmaceutical companies and specialized biotechnology companies, as well as technology being developed at universities and other research institutions. Our competitors have developed, are developing or will develop product candidates and processes competitive with our product candidate. Competitive therapeutic treatments include those that have already been approved or licensed and accepted by the medical community and any new treatments that enter the market. We believe that a significant number of products are currently under development, and may become commercially available in the future, for the treatment of conditions for which we may try to develop a product candidate. The biotechnology and pharmaceutical industries, including the oncology subsector, are characterized by rapidly evolving technologies, intense competition and strong defense of intellectual property and proprietary technologies. Any product candidate that we successfully commercialize may be competitive with currently marketed therapies and any new therapies commercialized in the future. 58 We are aware of several companies that are developing cancer immunotherapies and ADCs. Many of these companies are well-capitalized and, in contrast to us, have significant clinical experience, and may include our existing or future collaborators. In addition, these companies compete with us in recruiting scientific and managerial talent and the patient pool available for participation in clinical trials which could negatively impact our ability to execute our business plan. Our success will partially depend on our ability to develop and protect therapeutics that are more safe, pure, and potent than competing products. Our commercial opportunity and success will be reduced or eliminated if competing products that are safer, more effective, or less expensive than the therapeutics we develop are commercialized. If our product candidate is licensed, it will compete with a range of therapeutic treatments that are either in development or currently marketed. Many companies are active across various stages of development in the oncology subsector and are marketing and developing products that employ similar ADC and immunotherapy approaches. As of February 2026, there were approximately 900+ ADCs in clinical or preclinical development worldwide, of which the vast majority are being developed for the treatment of various cancer indications. Additionally, there are several large and small companies working on various immunotherapy approaches for treatment of cancer. Multiple companies are also involved in the development of ADC therapeutics and immunotherapies, including, but not limited to, AbbVie Inc., Abcure, Inc., ADC Therapeutics SA, Alligator Bioscience AB, Astellas Pharma, Inc., AstraZeneca plc, Celldex Therapeutics, Inc., Daiichi Sankyo Company, Ltd., Eucure Biopharma, a subsidiary of Biocytogen, Genentech, Inc., Gilead Sciences, Inc, GlaxoSmithKline, plc, Johnson & Johnson, Lyvgen Biopharma, Nextcure, Inc., Pfizer, Philogen S.p.A., Merck Sharpe & Dohme (MSD), Corbus Pharmaceuticals, and Rakuten Medical, Inc. We could also face competition with respect to specific targets, including the target of our ADC, MICVO, EDB+FN, by Philogen S.p.A., a Swiss based Biotechnology company, focused on generating antibody-cytokine fusions (immunocytokines) against cancers, using the L19 antibody specific to the EDB domain of Fibronectin fused to TNF, a potent inflammatory cytokine, which could pursue similar indications targeting EDB and stand out as the first non-ADC therapy pursuing EDB+FN. There are other emerging agents in key indications of interest including R/M HNSCC. Genmab’s EGFR and LGR5 targeting biclonal, petosemtamab, Bicara’s EGFR/TGF-beta targeting bifunctional, ficerafusp alfa (BCA101), and Johnson and Johnson’s EGFR and cMET bispecific antibody, amivantamab, are notable competitors that are targeting patient populations of interest to MICVO and pose a potentially significant threat to our clinical development strategy. Additionally, Corbus Pharmaceutical’s nectin-4 targeting ADC, CRB-701 has shown preliminary efficacy data and is a direct competitor given similarity in payload (MMAE) to MICVO, and comparable patient populations and clinical development timelines in R/M HNSCC. Other competitors may also include agents targeting specific segments such as HPV+ HNSCC, namely NeoTrail Therapeutics (formerly Hookipa)’s and PDS Biotech’s vaccines and agents such as Nanobiotix’s radioenhancer that may be used earlier in the treatment sequence. With the approval of pembrolizumab in the peri-operative setting based on Keynote-689, use of IO in the neoadjuvant and adjuvant settings may shift how HPV patients are treated in earlier lines of therapy. The implementation of using IO in the earlier disease settings could impact patient segmentation and treatment choices in the R/M setting. Furthermore, ADCs such as Gilead’s TROP-2 ADC, sacituzumab govitecan, Pfizer’s Nectin-4 targeting ADC, enfortumab vedotin and AZ’s AZD9592, a dual targeting ADC against EGFR and cMET are in clinical development in HNSCC. Enfortumab vedotin is currently pursuing a 1L HNSCC trial in combination with pembrolizumab thus adding to the crowded landscape of combo studies in the frontline setting. Additional competition may arise from other combination regimens being evaluated including but not limited to ficlatuzumab + cetuximab (2L), ivonescimab + ligufalimab (1L, CPS>1) and LN-145 + pembrolizumab (1L). Additionally, there is a wide array of activity in the development of immunotherapies for oncology which may be competitive with our preclinical discovery programs. Furthermore, if our product candidate is approved in oncology indications such as breast cancer, hematological and other cancers, they may compete with existing approaches to treating cancer including surgery, radiation, and drug therapy, including conventional chemotherapy, biological products, and targeted drug small molecule therapies. Many of our competitors have significantly greater scientific, research and development capabilities, as well as greater financial, technical, manufacturing, marketing, sales and supply resources or experience than we do. Competitive products may make any products we develop obsolete owing to treatment paradigm shifts or noncompetitive, reducing the addressable market before we recover the expense of developing and commercializing our product candidate. Such competitors could also recruit our employees, which could negatively impact our level of expertise and our ability to execute our business plan. We believe that our ability to successfully compete will depend on, among other things: • our ability to develop and protect therapeutics that are more effective and safer than competing products; • our ability to innovate with rapidly evolving technologies; 59 • the ease with which our products can be administered and the extent to which patients accept relatively new routes of administration; • the timing and scope of regulatory licenses for these products; • the price of our product candidate and whether coverage and adequate levels of reimbursement are available under health insurance plans; • our ability to utilize any abbreviated licensure pathways; and • the length of time we are granted market exclusivity for any product candidate we may develop that is licensed as a biological product under a Biologics License Application (BLA). Our business entails a significant risk of product liability, and if we are unable to obtain sufficient insurance coverage, such failure could have a material and adverse effect on our business, financial condition, results of operations and prospects. We expect to be exposed to significant product liability risks inherent in the development, testing and manufacturing of our product candidate and products, if approved. Product liability claims could delay or prevent completion of product candidate development programs. If we succeed in marketing products, such claims could result in an FDA investigation of the safety and effectiveness of our products, our third party manufacturer’s processes and facilities or our marketing programs and potentially a recall of our products or more serious enforcement action, including limitations on the approved indications for which our product candidate may be used or suspension or withdrawal of licenses. Regardless of the merits or eventual outcome, liability claims may also result in decreased demand for our products, injury to our reputation, costs to defend the related litigation, a diversion of management’s time and our resources, substantial monetary awards to trial participants or patients and a decline in our stock price. In addition, we may be subject to liability based on the actions of our existing or future collaborators in connection with their development of products using the FACT Platform or the APXiMAB Platform. Furthermore, clinical trial and product liability insurance is becoming increasingly expensive. As a result, we may be unable to maintain sufficient insurance at a reasonable cost to protect us against losses caused by product liability claims that could have a material and adverse effect on our business, financial condition, results of operations and prospects. Risks Related to Regulatory Licensure or Approval and Other Legal Compliance Matters The regulatory licensure and approval processes of the FDA and other comparable foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable and, if we are unable to obtain marketing licensure or approval for our product candidate, our business will be substantially harmed. The time required to obtain approval or licensure by the FDA and other comparable foreign regulatory authorities is unpredictable but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities. In addition, approval and licensure policies, regulations or the type and amount of clinical data necessary to gain approval or licensure may change during the course of a product candidate’s clinical development and may vary among jurisdictions. We have not obtained marketing approval or licensure for any product candidate, and it is possible that our existing product candidate, or any product candidate we may seek to develop in the future, will never obtain marketing approval or licensure. Our product candidate could fail to receive marketing licensure in the U.S. for many reasons, including the following: • the FDA may disagree with the design or implementation of our clinical trials; • we may be unable to demonstrate to the satisfaction of the FDA that the product candidate is safe, pure, and potent; • results of clinical trials may not meet the level of statistical significance required by the FDA for licensure; • we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; • the FDA may disagree with our interpretation of data from preclinical studies or clinical trials; • data collected from clinical trials of our product candidate may not be sufficient to support the submission of a BLA to the FDA or other submission or to obtain marketing licensure in the U.S.; • the FDA may find deficiencies with or fail to approve the manufacturing processes or facilities of third party manufacturers with which we contract for clinical and commercial supplies; and • the licensure policies or regulations of the FDA may significantly change in a manner rendering our clinical data insufficient for licensure. 60 This lengthy licensure process as well as the unpredictability of future clinical trial results may result in our failing to obtain regulatory licensure to market our product candidate, which would significantly harm our business, results of operations, financial condition and prospects. The FDA has substantial discretion in the licensure process and determining when or whether regulatory licensure will be obtained for our product candidate. Even if we believe the preliminary data collected from clinical trials of our product candidate is promising, such preliminary data may not be sufficient to support licensure by the FDA. In addition, even if we were to obtain licensure, regulatory authorities may approve our product candidate for fewer or more limited indications than we request, may grant a license contingent on the performance of costly post-marketing clinical trials, or may approve or license a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that product candidate. Any of the foregoing scenarios could materially harm the commercial prospects for our product candidate. Even if we receive regulatory licensure of our product candidate, we will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expense, and we may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our product candidate. If our product candidate is licensed or approved by regulatory authorities, they will be subject to ongoing regulatory requirements for manufacturing, labeling, packaging, storage, advertising, promotion, sampling, record-keeping, conduct of post-marketing studies, track and trace, serialization, post-market adverse event reporting, and submission of safety, purity, potency, efficacy and other post-market information, including both federal and state requirements in the United States and requirements of comparable foreign regulatory authorities. The FDA and foreign regulatory authorities will continue to monitor closely the safety profile of any product even after approval. If the FDA or foreign regulatory authorities become aware of new safety information after approval of a product candidate, they may require labeling changes or establishment of a Risk Evaluation and Mitigation Strategies (REMS), if not already established in pre-approval, or similar strategy, impose significant restrictions on its indicated uses or marketing, or impose ongoing requirements for potentially costly post approval studies or post-market surveillance. The FDA and comparable foreign regulatory authorities may conduct periodic inspections for compliance with regulatory requirements and standards. Later discovery of previously unknown problems with our product candidate, may result in consequences including, among other things: • restrictions and warnings on the labeling of a product; • restrictions on product distribution or use; • requirements to conduct post-marketing studies or clinical trials; • damage to relationships with any potential collaborators; • unfavorable press coverage and damage to our reputation; • restrictions on the marketing or manufacturing of our products, withdrawal of the product from the market or voluntary or mandatory product recalls; • fines, warning letters or holds on clinical trials; • refusal by the FDA and comparable foreign regulatory authorities to approve pending applications or supplements to approved applications filed by us or suspension or revocation of licenses; • product seizure or detention or refusal to permit the import or export of our product candidate; and • injunctions or the imposition of civil or criminal penalties. We, and any collaborators, must comply with requirements concerning advertising and promotion for our product candidate for which we or they obtain marketing licensure. Promotional communications with respect to prescription biological products are subject to a variety of legal and regulatory restrictions and must be consistent with the information in the product’s approved labeling. Thus, we, and any collaborators, will not be able to promote any products we develop for indications or uses for which the biological product is not licensed. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses and a company that is found to have improperly promoted off-label uses may be subject to significant liability. However, physicians may, in their independent medical judgment, prescribe legally available products for off-label uses. The FDA does not regulate the behavior of physicians in their choice of treatments. 61 If we decide to seek additional Breakthrough Therapy Designation and/or Fast Track Designation by the FDA, even if granted for any of our product candidate, may not lead to a faster development or regulatory review or licensure process and it does not increase the likelihood that our product candidate will receive marketing licensure. We may seek additional Breakthrough Therapy Designation and/or Fast Track Designation for our product candidate. For example, in February 2025, the FDA granted Fast Track Designation for use of MICVO in the treatment of adult patients with R/M HNSCC whose disease has progressed following treatment with platinum-based chemotherapy and an anti-PD-(L)1 antibody. The FDA may withdraw the Fast Track Designation if the clinical development program no longer meets the criteria for Fast Track Designation. There is no assurance that the FDA will grant these designations to any of our current or future product candidates. A Breakthrough Therapy is defined as a drug that is intended, alone or in combination with one or more other drugs or biological products, to treat a serious or life-threatening disease or condition and for which preliminary clinical evidence indicates that the drug or biological products may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. For product candidates that have been designated as Breakthrough Therapies, increased interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens. Drugs designated as Breakthrough Therapies by the FDA may also be eligible for other expedited approval programs, including Accelerated Approval and Priority Review, if they meet regulatory requirements for those other programs. Marketing applications submitted by sponsors of products in Fast Track development may qualify for Priority Review under the policies and procedures offered by the FDA, but the Fast Track Designation does not assure any such qualification. The FDA may withdraw any Fast Track Designation at any time. In any event, the receipt of a Breakthrough Therapy Designation and/or Fast Track Designation for a product candidate may not result in a faster development process, review or licensure compared to standard review and do not assure ultimate licensure by the FDA. In addition, even if our product candidate qualifies as a Breakthrough Therapy, the FDA may later decide that the product no longer meets the conditions for qualification. Additionally, the FDA may withdraw Fast Track Designation if it believes that the designation is no longer supported by data from our clinical development program. The FDA may withdraw any Fast Track Designation at any time. If we decide to seek Orphan Drug Designation for any of our current or future product candidates, we may be unsuccessful or may be unable to maintain the benefits associated with Orphan Drug Designation, including the potential for supplemental market exclusivity. We may seek Orphan Drug Designation for one or more of our current or future product candidates. For example, in May 2023, the FDA granted Orphan Drug Designation for MICVO in pancreatic cancer. Regulatory authorities in some jurisdictions, including the U.S. and Europe, may designate drugs or biological products for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biological product intended to treat a rare disease or condition, defined as a disease or condition with a patient population of fewer than 200,000 in the U.S., or a patient population greater than 200,000 in the U.S. when there is no reasonable expectation that the cost of developing and making available the drug in the U.S. will be recovered from sales in the U.S. for that drug or biological product. In the U.S., Orphan Drug Designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers. After the FDA grants Orphan Drug Designation, the identity of the drug or biological product and its potential orphan use are disclosed publicly by the FDA. Orphan Drug Designation does not convey any advantage in, or shorten the duration of, the regulatory review and licensure process. If a product that has Orphan Drug Designation subsequently receives the first FDA approval or licensure for a particular active ingredient for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including an NDA or BLA, to market the same drug or biological product for the same indication for seven years, except in limited circumstances such as a showing of clinical superiority to the product with orphan drug exclusivity or if the FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the biological product was designated. As a result, even if our product candidate receives orphan exclusivity, the FDA can still approve or license other drugs or biological products that have a different active ingredient for use in treating the same indication or disease. Further, the FDA can waive orphan exclusivity if we are unable to manufacture sufficient supply of our product. We may seek Orphan Drug Designation for our product candidate in additional orphan indications in which there is a medically plausible basis for the use of this product candidate. Even if we obtain Orphan Drug Designation, exclusive marketing rights in the U.S. may be limited if we seek licensure for an indication broader than the orphan designated indication and may be lost if the FDA later determines that the request for designation was materially defective or if we, through our manufacturer, are unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition. In addition, although we intend to seek Orphan Drug Designation for other product candidates, we may never receive these designations. 62 It is also possible that current or future litigation or action by Congress could change the scope of available orphan exclusivity. Any changes to the orphan drug provisions could change our opportunities for, or likelihood of success in obtaining, orphan drug exclusivity and would materially adversely affect our business, financial condition, results of operations, cash flows and prospects. Accelerated Approval by the FDA, even if granted, may not lead to a faster development or regulatory review or approval process and it does not increase the likelihood that our product candidate will receive marketing licensure. If not granted, we may be required to conduct additional non-clinical and clinical studies and trials beyond those that we currently contemplate. Even if we receive Accelerated Approval, if our confirmatory post-marketing trial does not verify clinical benefit, or if we do not comply with rigorous post-marketing requirements, the FDA may seek to withdraw Accelerated Approval. We plan to seek Accelerated Approval of MICVO and may seek approval of future product candidates through the FDA’s Accelerated Approval Program. For any licensure to market a biological product, we must provide the FDA and comparable foreign regulatory authorities with clinical data that adequately demonstrate the safety, purity, and potency of the product for the indication applied for in the NDA or BLA or other respective regulatory filings. The Accelerated Approval Program is one of several approaches used by the FDA to make prescription drugs or biological products more rapidly available for the treatment of serious or life-threatening diseases. Section 506(c) of the FDCA provides that the FDA may grant Accelerated Approval to “a product for a serious or life-threatening condition upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.” Licensure through the Accelerated Approval Program is subject, however, to the requirement that a sponsor perform adequate and well controlled post-marketing clinical trials to verify and describe the drug’s clinical benefit, where there is uncertainty as to the relationship of the surrogate endpoint to the clinical benefit, or of the observed clinical endpoint to ultimate outcome. Typically, clinical benefit is verified when post-marketing clinical trials show that the biological products provide a clinically meaningful positive therapeutic effect, that is, an effect on how a patient feels, functions, or survives. If required, these confirmatory trials must be underway prior to Accelerated Approval, pursuant to the Food and Drug Omnibus Reform Act of 2022 (FDORA) enacted in 2022 and under FDA’s draft guidance on “Accelerated Approval and Considerations for Determining Whether a Confirmatory Trial is Underway” made available in January 2025. In addition, Section 506(c) of the FDCA provides FDA authority to impose specific conditions on Accelerated Approval, including requiring post-approval study(ies) to verify and describe clinical benefit, and requiring submission of promotional materials during the pre-approval review period and, following approval and for such period thereafter as FDA determines appropriate, at least 30 days prior to dissemination. The statute also requires FDA, by no later than the date of Accelerated Approval, to specify conditions for required post-approval studies, which may include enrolment targets, protocol, and milestones (including a target completion date), and FDA may require such studies to be underway prior to approval or within a specified time period after approval. If such confirmatory post-marketing trials fail to confirm the product’s clinical profile or risks and benefits, or if we fail to conduct any required confirmatory trial with due diligence, or other evidence shows the product is not safe and effective under the conditions of use, the FDA may withdraw Accelerated Approval of the product. The FDA has broad discretion with regard to licensure through the Accelerated Approval Program and even if we believe that the Accelerated Approval Program is appropriate for one of our products, we cannot assure you that the FDA will ultimately agree. The FDA may also change its policies with respect to over Accelerated Approval over time. For example, in March 2023, the FDA announced the availability of draft guidance on “Clinical Trial Considerations to Support Accelerated Approval of Oncology Therapeutics,” in which the Agency outlined, and invited public comment on, its “preferred approach” of randomized controlled trials, including those that provide for longer term follow-up that could fulfill a post-marketing requirement to verify clinical benefit. The draft guidance, while not finalized, included statements where the FDA acknowledged that historically, single-arm trial designs and response endpoints have most commonly been used in oncology, but noted that such trials have limitations. Furthermore, even if we do obtain licensure through the Accelerated Approval Program, we may not experience a faster development process, review, or licensure compared to conventional FDA procedures. Even if the FDA reviews a BLA seeking Accelerated Approval, there can be no assurance that licensure will be granted on a timely basis, or at all. The FDA may disagree that the design of, or results from, our studies support Accelerated Approval. Additionally, the FDA could require us to conduct further studies or trials prior to granting licensure of any type, including by determining that licensure through the Accelerated Approval Program is not appropriate and that our clinical trials may not be used to support licensure through the conventional pathway. We might not be able to fulfill the FDA’s requirements in a timely manner, which would cause delays, or licensure might not be granted because our submission is deemed incomplete by the FDA. There also can be no assurance that after subsequent FDA feedback we will continue to pursue licensure through the Accelerated Approval Program. A failure to obtain licensure through the Accelerated Approval Program could result in a longer time period to obtain licensure of our products, could increase the cost of our products’ development, could delay our ability to commercialize our products and could significantly harm our financial position and competitive position in the marketplace. 63 Even if we receive licensure for one of our products through the Accelerated Approval Program, we will be subject to rigorous post-marketing requirements, including the completion of one or more confirmatory post-marketing trials as the FDA may require, to verify the clinical benefit of the product, and submission to the FDA of all promotional materials prior to their dissemination. These requirements could adversely impact the timing of the commercial launch of the product. Even if we do receive Accelerated Approval, we may not experience a faster development or regulatory review or licensure process. Further, receiving Accelerated Approval does not provide assurance of ultimate full FDA licensure. The FDA could seek to withdraw Accelerated Approval for multiple reasons, including if we fail to conduct any required confirmatory post-marketing trial with due diligence, our confirmatory post-marketing trial does not confirm the predicted clinical benefit, other evidence shows that the product is not safe, pure, or potent under the conditions of use, or we disseminate promotional materials that are found by the FDA to be false and misleading. Further description of the expedited withdrawal process was released by the FDA in the recent draft guidance Expedited Program for Serious Conditions – Accelerated Approval of Drugs and Biologics (December 2024). Moreover, Congress is considering potential changes to the Accelerated Approval Program that could impact our ability to obtain Accelerated Approval, or increase the burdens associated with post-marketing requirements in the event we do obtain Accelerated Approval. In particular, the FDA must specify certain conditions for required post approval studies for products that receive Accelerated Approval, which may include enrollment targets and milestones, including the target date for study completion, by the time the drug is approved. The FDA may also require post approval studies to be underway at the time of Accelerated Approval or within a specified time period following Accelerated Approval for such drugs, and must explain any instances where it does not require such studies. FDA’s January 2025 draft guidance on Accelerated Approval and Considerations for Determining Whether a Confirmatory Trial is Underway , while not finalized, suggests that FDA generally intends to consider a confirmatory trial to be "underway" prior to Accelerated Approval if (1) the trial has a target completion date that is consistent with diligent and timely conduct of the trial, considering the nature of the trial’s design and objectives, (2) the sponsor’s progress and plans for post approval conduct of the trial provide sufficient assurance to expect timely completion of the trial, and (3) enrollment of the confirmatory trial has been initiated. Any delay in obtaining, or inability to obtain, licensure through the Accelerated Approval Program, or any issues in maintaining approval granted under the Accelerated Approval Program, would delay or prevent commercialization of our products, and would materially adversely affect our business, financial condition, results of operations, cash flows and prospects. If foreign regulatory authorities approve biosimilar versions of our product candidate that receive marketing approval, or such authorities do not grant our product candidate appropriate periods of data or market exclusivity before approving generic versions of our product candidate, the sales of our product candidate could be adversely affected. In the EU and the UK, innovative medicinal products are authorized based on a full marketing authorization application and conditional authorization (as opposed to an application for marketing authorization that relies on data in the marketing authorization dossier for another, previously approved medicinal product). Applications for marketing authorization for innovative medicinal products must contain, inter alia , the results of pharmaceutical tests, preclinical tests and clinical trials conducted with the medicinal product for which marketing authorization is sought. A marketing authorization can be obtained via the centralized procedure or the national procedure. The centralized procedure results in a single marketing authorization, issued by the European Commission (based on the opinion of the EMA), which is valid across the entire European Economic Area (EEA) which comprises the EU, Iceland, Liechtenstein and Norway. The centralized procedure is compulsory for human drugs that are (i) derived from biotechnology processes, such as genetic engineering; (ii) contain a new active substance indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative diseases, autoimmune and other immune dysfunctions and viral diseases; (iii) designated orphan medicines; and (iv) advanced-therapy medicines, such as gene therapy, somatic cell therapy or tissue-engineered medicines. The centralized procedure may at the request of the applicant also be used in certain other cases. The centralized procedure would be mandatory for the product candidate we are developing. 64 Where an applicant for a marketing authorization submits a full dossier containing its own pharmaceutical, preclinical tests and clinical trials data, and where the application does not fall within the ‘global marketing authorization’ of an existing medicinal product, reference product candidates may receive eight years of data exclusivity and an additional two years of market exclusivity, upon grant of the marketing authorization. If granted, during the data exclusivity period, applicants for approval of biosimilars cannot rely on data contained in the marketing authorization dossier submitted for the already authorized, or reference product candidate, to support their application. The market exclusivity period prevents a successful biosimilar applicant from commercializing its product in the EU until 10 years have elapsed from the initial marketing authorization of the reference product in the EU, but a biosimilar marketing authorization application can be submitted during this time. The overall 10-year market exclusivity period can further be extended by one more year if, during the first eight years of those 10 years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies. However, even if a compound is considered to be a new active substance and the innovator is able to gain the period of data and market exclusivity, provided that no other intellectual property or regulatory exclusivities apply, another unrelated company could also apply for a marketing authorization and market another competing medicinal product for the same therapeutic indication if such company obtained its own marketing authorization based on a separate marketing authorization application based on a full self-standing scientific data package supporting the application. In the EU, there is a special regime for biosimilars, or biological medicinal products that are similar to a reference medicinal product but that do not meet the definition of a generic medicinal product, for example, because of differences in raw materials or manufacturing processes. For such products, the results of appropriate preclinical testing or clinical trials must be provided, and guidelines from the EMA detail the type of quantity of supplementary data to be provided for different types of biological products. There are currently no such guidelines for complex biological products such as gene or cell therapy medicinal products, and so in the short term it is unlikely that biosimilars of those products will be approved in the EU. However, guidance from the EMA states that they will be considered in the future in light of the scientific knowledge and regulatory experience gained at the time. In the EU, the criteria for designating an “orphan medicinal product” are similar in principle to those in the U.S. A medicinal product may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition (2) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the EU to justify investment and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those affected by the condition. The application for Orphan Drug Designation must be submitted before the marketing authorization application. Orphan Drug Designations entitle a party to financial incentives such as reduction of fees or fee waivers and are, upon grant of a marketing authorization, entitled to 10 years of market exclusivity. During the 10-year market exclusivity period, the EMA cannot accept another marketing authorization application, or grant a marketing authorization or accept an application to extend an existing marketing authorization, for the same therapeutic indication, in respect of a similar medicinal product. Orphan Drug Designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process. The ten-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for Orphan Drug Designation, for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity. At any time, a marketing authorization may be granted to a similar product for the same indication if: 1. the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior; 2. the holder of the marketing authorization for the original orphan medicinal product has given his consent to the second applicant; or 3. the holder of the marketing authorization for the original orphan medicinal product is unable to supply sufficient quantities of the medicinal product. Although the UK has left the EU, its regulatory legal framework provides for similar periods of protection (namely regulatory data exclusivity, marketing protection and market exclusivity). Competition that our product candidate may face from biosimilar versions of our product candidate could materially and adversely impact our future revenue, profitability and cash flows and substantially limit our ability to obtain a return on the investments we have made in the product candidate. Our future revenues, profitability and cash flows could also be materially and adversely affected and our ability to obtain a return on the investments we have made in this product candidate may be substantially limited if our product candidate, if and when approved, are not afforded the appropriate period of non-patent exclusivity. 65 Our failure to obtain regulatory approval in international jurisdictions would prevent us from marketing our product candidate outside the U.S. and the sales of our product candidate could be adversely affected. In order to market and sell our product candidate in other jurisdictions, we must obtain separate marketing approvals for those jurisdictions and comply with their numerous and varying regulatory requirements. We may not obtain foreign regulatory approvals on a timely basis, or at all. The approval procedure varies among countries and can involve additional testing. The time required to obtain approval may differ substantially from that required to obtain FDA approval. The regulatory approval process outside the U.S. generally includes all of the risks associated with obtaining FDA approval. In addition, in many countries outside the U.S., product reimbursement approvals must be secured before regulatory authorities will approve the product for sale in that country. Obtaining foreign regulatory approvals and compliance with foreign regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction of our product candidate in certain countries. Further, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries and regulatory approval in one country does not ensure approval in any other country. Our failure to obtain approval of our product candidate by foreign regulatory authorities may negatively impact the commercial prospects of such product candidate and our business prospects could decline. The failure to obtain required regulatory clearances or approvals for any companion diagnostic tests that we may pursue may prevent or delay approval of our product candidate. Moreover, the commercial success of a product candidate that requires a companion diagnostic will be tied to the receipt of any required regulatory clearances or approvals and the continued availability of such tests. We may seek to identify patient subsets within a disease category that may derive selective and meaningful benefit from the product candidate we are developing. Through collaborations or license agreements, companion diagnostics may help us to more accurately identify patients within a particular subset, both during our clinical trials and in connection with the commercialization of our product candidate, if approved. In connection with the clinical development of our product candidate for certain indications, we may work with collaborators to develop or obtain access to companion diagnostic tests to identify appropriate patients for our product candidate. We may rely on third parties for the development, testing and manufacturing of these companion diagnostics, the application for and receipt of any required regulatory clearances or approvals, and the commercial supply of these companion diagnostics. Companion diagnostics are subject to regulation by the FDA and comparable foreign regulatory authorities as a medical device and may require separate regulatory authorization prior to commercialization. The FDA and foreign regulatory authorities regulate companion diagnostics as medical devices that will likely be subject to clinical trials in conjunction with the clinical trials for a product candidate, and which will require separate regulatory clearance or approval prior to commercialization. This process could include additional meetings with health authorities, such as a pre-submission meeting and the requirement to submit an investigational device exemption (IDE). In the case of a companion diagnostic that is designated as “significant risk device,” approval of an IDE by the FDA and an IRB is required before such diagnostic is used in conjunction with the clinical trials for a corresponding product candidate. We or our third party collaborators may fail to obtain the required regulatory clearances or approvals, which could prevent or delay approval of our product candidate. In addition, the commercial success of our product candidate that requires a companion diagnostic will be tied to and dependent upon the receipt of required regulatory clearances or approvals and the continued ability of such third parties to make the companion diagnostic commercially available to us on reasonable terms in the relevant geographies. Our relationships with customers, physicians and third party payors are subject, directly or indirectly, to federal and state healthcare fraud and abuse laws, false claims laws, and other healthcare laws and regulations. If we are unable to comply or have not fully complied with these laws, we could face substantial penalties. Healthcare providers, physicians and third party payors in the U.S. and elsewhere will play a primary role in the recommendation and prescription of any product candidate for which we obtain marketing licensure. Our current and future arrangements with healthcare professionals, principal investigators, consultants, customers, drug wholesalers/distributors, pharmacy benefit managers, and third party payors subject us to various federal and state fraud and abuse laws and other healthcare laws that may constrain the business or financial arrangements and relationships through which we research, develop, sell, market and distribute our product candidate, if we obtain marketing licensure. In particular, the research of our product candidate, as well as the promotion, sales and marketing of healthcare items and services, as well as certain business arrangements in the healthcare industry, are subject to extensive laws designed to prevent fraud, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, structuring and commission(s), certain customer incentive programs and other business or financial arrangements. 66 Ensuring that our business arrangements with third parties comply with applicable healthcare laws and regulations will likely be costly. The shifting compliance environment and the need to build and maintain robust and expandable systems to comply with multiple jurisdictions with different compliance or reporting requirements increases the possibility that a healthcare company may run afoul of one or more of the requirements. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations, or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties; damages; fines; disgorgement; imprisonment; exclusion from participating in government-funded healthcare programs, such as Medicare and Medicaid; additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws; contractual damages; reputational harm; and/or the curtailment or restructuring of our operations. If the physicians or other providers or entities with whom we expect to do business are found not to be in compliance with applicable laws, they may be subject to significant criminal, civil or administrative sanctions, including exclusion from government-funded healthcare programs. Even if resolved in our favor, litigation or other legal proceedings relating to healthcare laws and regulations may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development, manufacturing, sales, marketing or distribution activities. Uncertainties resulting from the initiation and continuation of litigation or other proceedings relating to applicable healthcare laws and regulations could have an adverse effect on our ability to compete in the marketplace. Even if we commercialize our product candidate, it or any other product candidate that we develop, may become subject to unfavorable pricing regulations or third party coverage or reimbursement practices, which could harm our business. Significant uncertainty exists as to the coverage and reimbursement status of any products for which we may obtain regulatory licensure. Our ability to successfully commercialize our product candidate will depend, in part, on the extent to which coverage and adequate reimbursement for any products for which we obtain marketing authorization will be available from third party payors, including government health care programs, managed care providers, private health insurers, health maintenance organizations and other organizations. In the U.S., no uniform policy for coverage and reimbursement for pharmaceutical products exists among third party payors. Third party payors decide which medications they will pay for and establish reimbursement levels; therefore, coverage and reimbursement for our product candidate for which we may obtain marketing authorization could differ significantly from payor to payor. One payor’s determination to provide coverage for a product does not assure that other payors will also provide coverage and reimbursement for the product. Payors consider a number of factors when determining whether to cover a new product, including, for example, whether the product is a covered benefit under its health plan; safe, effective and medically necessary; appropriate for the specific patient; cost-effective; and neither experimental nor investigational. Third party payors may also limit coverage to specific products on an approved list, or formulary, which might not include all of the FDA-approved products for a particular indication if they are granted Accelerated Approval. Failure to obtain or maintain coverage and adequate reimbursement for our product candidate, if approved, could limit our ability to market the products and decrease our ability to generate revenue. Moreover, a payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved. The process for determining whether a payor will provide coverage for a product may be separate from the process for setting the reimbursement rate that the payor will pay for the product. Even if coverage is provided, the approved reimbursement amount may not be high enough to allow us to establish or maintain pricing sufficient to realize a sufficient return on our investment. We cannot be sure that coverage and reimbursement will be available for any product that we commercialize and, if reimbursement is available, what the level of reimbursement will be. Limitation on coverage and reimbursement may impact the demand for, or the price of, and our ability to successfully commercialize any product candidate that we develop. For products administered under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because of the higher prices often associated with such drugs. Additionally, separate reimbursement for the product itself may or may not be available. Instead, the hospital or administering physician may be reimbursed only for providing the treatment or procedure in which our product is used. 67 Further, increasing efforts by third party payors in the U.S. and abroad to cap or reduce healthcare costs may cause payor organizations to limit both coverage and the level of reimbursement for newly approved products and, as a result, they may not cover or provide adequate payment for our product candidate. In order to secure coverage and reimbursement for any product that might be approved for sale, we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of our products, in addition to the costs required to obtain FDA or comparable marketing authorizations or approvals. Additionally, we may also need to provide permissible discounts to purchasers, private health plans or government healthcare programs. Our product candidate may nonetheless not be considered medically necessary or cost-effective. If third party payors do not consider a product to be cost-effective compared to other available therapies, they may not cover the product after marketing authorization or approval as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow a company to sell its products at a profit. We expect to experience pricing pressures from third party payors in connection with the potential sale of our product candidate. The regulations that govern marketing approvals, coverage and reimbursement for new drug products vary widely from country to country. Current and future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. In some countries, the pricing for a drug must be approved before the drug may be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted. There can be no assurance that any country will allow reimbursement and pricing arrangements for our product candidate that are sufficient to recoup our investment. Enacted and future healthcare legislation may increase the difficulty and cost for us to progress our clinical programs and obtain marketing licensure or approval of and commercialize our product candidate and may affect the prices we may set. In the U.S. and other jurisdictions, there have been, and we expect there will continue to be, a number of legislative and regulatory changes and proposed changes to the healthcare system that could affect results of our future operations. In particular, there have been and continue to be a number of initiatives at the U.S. federal and state levels that seek to reduce healthcare costs and improve the quality of healthcare. For example, the Inflation Reduction Act (IRA), which was signed into law on August 16, 2022, allows Medicare to: beginning in 2026, establish a “maximum fair price” for a fixed number of pharmaceutical and biological products covered under Medicare Parts B and D following a price negotiation process with the Centers for Medicare and Medicaid Services (CMS); and, beginning in 2023, penalize drug companies that raise prices for products covered under Medicare Parts B and D faster than inflation, among other reforms. It is unclear how future regulatory actions to implement the IRA, as well as the outcome of pending litigation against the IRA, may affect our products and future profitability. See Part I, Item 1, Government Regulation – Healthcare and Data Privacy Regulation – Healthcare Reform of this Annual Report on Form 10-K for additional detail on recent healthcare reform efforts that could affect our operations. We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the extent to which state and federal governments cover particular healthcare products and services and could limit the amounts that federal and state governments will pay for healthcare items and services. This could result in reduced demand for any product candidate we develop or could result in additional pricing pressures. In markets outside of the U.S., reimbursement and healthcare payment systems vary significantly by country and many countries have instituted price ceilings on specific products and therapies. The price control regulations outside of the U.S. can have a significant impact on the profitability of a given market, and further uncertainty is introduced if and when these laws change. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action in the U.S. or any other jurisdiction. If we, or any third parties we may engage, are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we, or these third parties, are not able to maintain regulatory compliance, our product candidate may lose any regulatory licensure or approval that may have been obtained and we may not achieve or sustain profitability. Our operations are subject to trade controls, sanctions and anti-corruption laws, and noncompliance could result in significant penalties and operational disruption. We engage third parties and vendors and may conduct activities across multiple jurisdictions. As a result, our operations may be subject to import and export controls, economic sanctions, customs requirements, and anti-corruption and anti-bribery laws administered by the United States and foreign authorities. These regulatory regimes are complex, change frequently, and may be subject to differing interpretations. Any failure, or alleged failure, by us or by third parties acting on our behalf to comply with these requirements could result in investigations, civil or criminal penalties, fines, loss of export privileges, contract termination, reputational harm, or increased compliance costs. Even allegations of noncompliance could divert management attention and materially adversely affect our business, financial condition and results of operations. 68 The biopharmaceutical industry is subject to extensive regulatory obligations and policies that may be subject to significant and abrupt change, including due to judicial challenges, election cycles, and resulting regulatory updates and changes in policy priorities. On June 28, 2024, the U.S. Supreme Court issued an opinion holding that courts reviewing agency action pursuant to the Administrative Procedure Act (APA) “must exercise their independent judgment” and “may not defer to an agency interpretation of the law simply because a statute is ambiguous.” The decision will have a significant impact on how lower courts evaluate challenges to agency interpretations of law, including those by the Department of Health and Human Services (HHS), CMS, FDA and other agencies with significant oversight of the biopharmaceutical industry. The new framework is likely to increase both the frequency of such challenges and their odds of success by eliminating one way in which the government previously prevailed in such cases. As a result, significant regulatory policies will be subject to increased litigation and judicial scrutiny. In addition, federal agency priorities, leadership, policies, rulemaking, communications, spending, and staffing may be significantly impacted by election cycles and legislative developments. For example, the current presidential administration’s commitment to significantly reduce government spending through cuts to federal healthcare programs and reductions in the workforces of key government agencies, such as HHS, FDA and CMS. Efforts by the current administration to limit federal agency budgets or personnel may result in reductions to agency budgets, employees, and operations. The administration and agencies have also made abrupt announcements about new or changed regulatory policies, such as policies related to the use of artificial intelligence to review product applications. And, the recent federal government shutdown may prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews or other regulatory activities, and may significantly impact the ability of the FDA to timely review and process our regulatory submissions. These developments may lead to greater uncertainty regarding FDA policies, slower response times and longer review periods, potentially affecting our ability to progress development of our product candidate or obtain regulatory approval for our product candidate. Any resulting changes in regulation may result in unexpected delays, increased costs, or other negative impacts on our business that are difficult to predict. Actual or perceived failures to comply with applicable data protection, privacy and security laws, regulations, standards and other requirements could adversely affect our business, operations, and financial condition. In the ordinary course of business, we collect, receive, store, process, generate, use, transfer, disclose, make accessible, protect, secure, dispose of, transmit, and share, or collectively, process, personal data and other sensitive information, including proprietary and confidential business data, trade secrets, intellectual property, sensitive third party data, business plans, transactions, clinical trial data and financial information or collectively, sensitive data. Any failure or perceived failure by us to comply with federal, state or foreign laws or self-regulatory standards could result in negative publicity, diversion of management time and effort and proceedings against us by governmental entities or others. In the U.S., federal, state, and local governments have enacted numerous data privacy and security laws, including data breach notification laws, personal data privacy laws, consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), and other similar laws (e.g., wiretapping laws). Most healthcare providers, including certain research institutions from which we may obtain patient health information, are subject to privacy and security regulations promulgated under the Health Insurance Portability and Accountability Act of 1996 (HIPPA), as amended by the Health Information Technology for Economic and Clinical Health Act (HITECH). We are not currently acting as a covered entity (health plans, health care clearinghouses and certain health care providers) or business associate (individuals or entities that create, receive, maintain or transmit individually identifiable health information in connection with providing a service for or on behalf of a covered entity, as well as their covered subcontractors) under HIPAA and therefore are not directly regulated under HIPAA. However, any person may be prosecuted under HIPAA’s criminal provisions either directly or under aiding-and-abetting or conspiracy principles. Consequently, depending on the facts and circumstances, we could face substantial criminal penalties if we knowingly receive individually identifiable health information from a HIPAA-covered healthcare provider or research institution that has disclosed individually identifiable health information in a manner that is not authorized or permitted under HIPAA. In addition, in the future, we may maintain sensitive personal information, including health-related information, that we receive throughout the clinical trial process, in the course of our research collaborations and/or directly from individuals (or their healthcare providers) who may enroll in patient assistance programs if we choose to implement these types of programs. As a result, we may be subject to data privacy and security laws protection such information, including state laws requiring notification of affected individuals and state regulators in the event of a breach of personal information, which is a broader class of information than the health information protected by HIPAA. 69 In the past few years, numerous U.S. states have enacted health-specific or comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights concerning their personal data. For example, Washington’s My Health My Data Act regulates consumer health data, which includes personal information identifies a consumer’s past, present, or future physical or mental health. However, the My Health My Data Act provides exemptions for personal data used or shared in research, including data subject to 45 C.F.R. Parts 46, 50, and 56. Another example, the California Consumer Privacy Act of 2018 (CCPA), as amended by the California Privacy Rights Act of 2020 (CPRA), collectively CCPA, creates individual data privacy rights for consumers and operational requirements for companies, including placing increased privacy and security obligations on entities handling certain personal information of consumers or households; imposes additional data protection obligations on covered businesses, including additional consumer rights processes; limitations on data uses; new audit requirements for higher risk data; and opt outs for certain uses of sensitive data. The CCPA gives California residents expanded rights to access and delete their personal information, opt out of certain personal information sharing and receive detailed information about how their personal information is used. The CCPA provides for civil penalties for violations, private right of action for data breaches, and created a new California data protection agency authorized to issue substantive regulations and could result in increased privacy and information security enforcement and litigation. Similar laws have been adopted or proposed in other states and at the federal level, and if passed, such laws may have potentially conflicting requirements that would make compliance challenging. While these laws generally include exemptions for health-related data such as clinical trial data, they add layers of complexity to compliance in the U.S. market and could increase our compliance costs and adversely affect our business. In the event we are subject to or affected by HIPAA, the CCPA, or other privacy and data protection laws, any liability from failure to comply with the requirements of these laws could adversely affect our financial condition. Additionally, the FTC and many state attorneys general are interpreting existing federal and state consumer protection laws to impose evolving standards for the collection, use, dissemination and security of health-related and other personal information and in particular health information. Courts may also adopt the standards for fair information practices promulgated by the FTC, which concern consumer notice, choice, security and access. Consumer protection laws require us to publish statements that describe how we handle personal information and choices individuals may have about the way we handle their personal information. If such information that we publish is considered untrue, we may be subject to government claims of unfair or deceptive trade practices, which could lead to significant liabilities and consequences. Furthermore, according to the FTC, violating consumers’ privacy rights or failing to take appropriate steps to keep consumers’ personal information secure may constitute unfair acts or practices in or affecting commerce in violation of Section 5 of the FTC Act. The FTC has also been active with respect to enforcement of its Health Breach Notification Rule and in scrutinizing the use and disclosure of sensitive personal information. The FTC finalized changes to the Health Breach Notification Rule in April 2024. Additionally, the FTC published an advance notice of proposed rulemaking in 2022 on commercial surveillance and data security, and may implement new trade regulation rules or other regulatory alternatives concerning the ways in which companies (1) collect, aggregate, protect, use, analyze, and retain consumer data, as well as (2) transfer, share, sell, or otherwise monetize that data in ways that are unfair or deceptive in the coming years. Outside the U.S., an increasing number of laws, regulations, and industry standards govern data privacy and security. For example, the European Union General Data Protection Regulation (EU GDPR) and the United Kingdom’s GDPR (UK GDPR), collectively GDPR, impose strict requirements for the processing of personal data. The GDPR imposes a number of compliance obligations including accountability and transparency requirements, requirements to process personal data lawfully, obligations to consider data protection as any new products or services are developed and designed, obligations to implement appropriate technical and organizational security measures to safeguard personal data and to report certain personal data breaches, obligations to comply with data protection rights of data subjects and additional requirements around the processing of special categories of personal data, including health and genetic data. The GDPR have restrictions on transfers of personal data from their jurisdiction to other jurisdictions. Companies may be subject to robust regulatory enforcement of data protection requirements and potential fines for noncompliance of up to €20 million (under the EU GDPR) or £17.5 million (under the UK GDPR) or up to 4% of the annual global turnover of the preceding year for the noncompliant company, whichever is greater. Although we work to comply with applicable laws, regulations and standards, our contractual obligations and other legal obligations, these requirements are evolving and may be modified, interpreted and applied in an inconsistent manner from one jurisdiction to another, and may conflict with one another or other legal obligations with which we must comply. Any failure or perceived failure by us or our employees, representatives, contractors, consultants, collaborators, or other third parties to comply with such requirements or adequately address privacy and security concerns, even if unfounded, could result in additional cost and liability to us, damage our reputation, and adversely affect our business and results of operations. 70 If we or our third party manufacturers and suppliers fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have an adverse effect on the success of our business. We are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Our research and development activities involve the use of biological and hazardous materials and produce hazardous waste products. We cannot eliminate the risk of contamination or injury from these materials, which could cause an interruption of our commercialization efforts, research and development efforts and business operations, environmental damage resulting in costly clean-up and/or liabilities under applicable laws and regulations. We generally contract with third parties for the disposal of these materials and wastes and cannot eliminate the risk of accidental contamination or injury. Upon an event of this nature, we may be held liable for any resulting damages and such liability could exceed our resources and federal, state or other applicable authorities may curtail our use of certain materials and/or interrupt our business operations. Environmental laws and regulations are complex, change frequently and have tended to become more stringent and we may incur substantial costs to comply. Current or future laws and regulations may impair our research, development or production efforts. Failure to comply with these laws and regulations may result in substantial fines, penalties or other sanctions. Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials or other work-related injuries, this insurance may not provide adequate coverage against potential liabilities. We are subject to U.S. and certain foreign export and import controls, anti-corruption laws and anti-money laundering laws and regulations. We can face criminal liability and other serious consequences for violations, which can harm our business. We are subject to various federal, state, and foreign government export and import laws and regulations, anti-bribery and anti-money laundering laws in the U.S. and countries in which we conduct activities. Anti-corruption laws are interpreted broadly and prohibit companies and their employees, agents, contractors and other collaborators from authorizing, promising, offering or providing, directly or indirectly, improper payments or anything else of value to recipients in the public or private sector. We may engage third parties for clinical trials outside of the U.S., to sell our products abroad once we enter a commercialization phase and/or to obtain necessary permits, licenses, patent registrations and other regulatory approvals. We may also have direct or indirect interactions with officials and employees of government agencies or government-affiliated hospitals, universities and other organizations. We can be held liable for the corrupt or other illegal activities of our employees, agents, contractors and other collaborators, even if we do not explicitly authorize or have actual knowledge of these activities. Any violations of the laws and regulations described above may result in substantial civil and criminal fines and penalties, imprisonment, the loss of export or import privileges, debarment, tax reassessments, breach of contract and fraud litigation, reputational harm and other consequences. Risks Related to Employee Matters, Managing Our Growth and Other Risks Related to Our Business If we fail to attract and retain qualified senior management and key scientific and medical personnel, our business may be materially and adversely affected. Our success depends in part on our continued ability to attract, retain and motivate highly qualified management, clinical, and scientific personnel. We are highly dependent upon members of our senior management, including Thomas Civik, currently serving as Interim Chief Executive Officer of the Company, Jitendra Wadhane, who serves as Principal Financial and Accounting Officer, as well as our senior scientists, senior medical personnel and other members of our senior management team. The loss of one or more of our executive officers, senior scientists, senior medical personnel and other members of our senior management team could delay or prevent the successful development of our product pipeline, the initiation and completion of our clinical trials or the commercialization of our product candidate or any future product candidate. Competition for qualified personnel in the pharmaceutical, biopharmaceutical and biotechnology field is intense due to the limited number of individuals who possess the skills and experience required by our industry. We may need to hire additional personnel as we expand our clinical development and if we initiate commercial activities. We may not be able to attract and retain quality personnel on acceptable terms, or at all. In addition, to the extent we hire personnel from competitors, we may be subject to allegations that they have been improperly solicited or that they have divulged proprietary or other confidential information, or that their former employers own their research output. Our employees, consultants and collaborators may engage in misconduct or other improper activities, including insider trading and non-compliance with regulatory standards and requirements. We are exposed to the risk that our employees, consultants, distributors, and collaborators may engage in fraudulent or illegal activity. Misconduct by these parties could include intentional, reckless or negligent conduct or disclosure of unauthorized activities to us that violates the regulations of the FDA, U.S. regulators and non-U.S. regulators, including those laws requiring the reporting of true, complete and accurate information to such regulators. 71 We have adopted a code of conduct applicable to all of our employees, officers, directors, including consultants, but it is not always possible to identify and deter misconduct by our employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations. If any such actions are instituted against us and we are not successful in defending ourselves or asserting our rights, those actions could result in the imposition of significant fines or other sanctions, including the imposition of civil, criminal and administrative penalties, damages, monetary fines, contractual damages, reputational harm, any of which could adversely affect our ability to operate our business and our results of operations. Whether or not we are successful in defending against such actions or investigations, we could incur substantial costs, including legal fees, and divert the attention of management in defending ourselves against any of these claims or investigations. We currently have no marketing, sales, or distribution infrastructure and both establishing this infrastructure or outsourcing this function to a third party carries substantial risks to us. We currently have no marketing, sales, or distribution capabilities because our product candidate is still in clinical development. If our product candidate completes clinical development and is approved, we intend to either establish a sales and marketing organization with technical expertise and supporting distribution capabilities to commercialize our product candidate in a legally compliant manner, or to outsource this function to a third party. There are risks involved if we decide to establish our own sales and marketing capabilities or enter into arrangements with third parties to perform these services. To the extent that we enter into collaboration agreements with respect to marketing, sales or distribution, our product revenue may be lower than if we directly marketed or sold any approved products. Such collaborative arrangements with partners may place the commercialization of our products outside of our control and would make us subject to a number of risks, including that we may not be able to control the amount or timing of resources that our collaborative partner devotes to our products or our collaborator’s willingness or ability to complete its obligations, and our obligations under our arrangements may be adversely affected by business combinations or significant changes in our collaborators’ business strategy. If we are unable to enter into these arrangements on acceptable terms or at all, we may not be able to successfully commercialize any approved products. If we are not successful in commercializing any approved products, either on our own or through collaborations with one or more third parties, our future product revenue will suffer and we may incur significant additional losses, which would have a material adverse effect on our business, financial condition, and results of operations. Our information technology systems, or those of any of our existing or future CROs, manufacturers, other contractors, consultants, or collaborators, may be compromised, which could result in additional costs, significant liabilities, harm to our reputation and material disruption of our operations. In the ordinary course of our business, we collect, process, and store proprietary, confidential, and sensitive information, including personal information (including health information), intellectual property, trade secrets, and proprietary business information owned or controlled by ourselves or other parties. Despite the implementation of security measures, our information technology systems and infrastructure, and those of our current and any future CROs, manufacturers, other contractors, consultants, existing or future collaborators and other third party service providers are vulnerable to damage from various methods, including cybersecurity attacks, breaches, errors, malfeasance, or other technological failures, which can include, among other things, computer viruses, unauthorized access attempts, including third parties gaining access to systems using stolen or inferred credentials, ransomware attacks, denial-of-service attacks, phishing attempts, service disruptions, natural disasters, fire, terrorism, war and telecommunication and electrical failures. As the cyber-threat landscape evolves, these attacks are growing in frequency, sophistication and intensity, and are becoming increasingly difficult to detect. Furthermore, because the techniques used to obtain unauthorized access to, or to sabotage, systems change frequently and often are not recognized until launched against a target, we may be unable to anticipate these techniques or implement adequate preventative measures. We may also experience security breaches that may remain undetected for an extended period. While we have implemented security measures designed to protect against security breaches, there can be no assurance that our security measures or those of our service providers, partners and other third parties, will be effective in protecting against all security breaches and material adverse effects on our business that may arise from such breaches. The recovery systems, security protocols, network protection mechanisms and other security measures that we (and our third parties) have integrated into our platform, systems, networks and physical facilities, which are designed to protect against, detect and minimize security breaches, may not be adequate to prevent or detect service interruption, system failure or data loss. 72 If such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our product candidate development program and our business operations including without limitation, disruptions of our drug development programs, delays in our regulatory approval efforts, regulatory investigations or enforcement actions, litigation, indemnity obligations, negative publicity, and financial loss and significant liabilities. In addition, system failures could cause the loss, theft, exposure, or unauthorized access or use of valuable clinical trial data as a result of accidents, errors or malfeasance by our employees, independent contractors or others working with us or on our behalf or otherwise disrupt our clinical activities and be expensive and time-consuming to remedy. Some of the federal, state and foreign government legal requirements include obligations of companies to notify individuals of security breaches involving particular personally identifiable information, which could result from breaches experienced by us or by our vendors, contractors or organizations with which we have formed strategic relationships. Notifications and follow-up actions related to a security breach could impact our reputation and cause us to incur significant costs, including legal expenses and remediation costs. For example, the loss of clinical trial data from completed, ongoing or future clinical trials involving our product candidate could result in delays in our regulatory licensure efforts and significantly increase our costs to recover or reproduce the lost data. Any breach of our computer systems may result in a loss of data or compromised data integrity across many of our programs in various stages of development. We may be required to expend resources; modify our business activities and practices; or modify our operations, including our development program activities; or information technology in an effort to comply with applicable data protection laws, privacy policies and data protection obligations. To the extent that any disruption or security breach were to result in a loss of, or damage to, our data, or inappropriate disclosure of confidential or proprietary information, we could be exposed to litigation and governmental investigations, the further development and commercialization of our product candidate could be delayed and we could be subject to significant fines or penalties for any noncompliance with certain state, federal or international privacy and security laws. Our insurance policies may not be adequate to compensate us for the potential losses arising from any such disruption, failure or security breach, may not cover all claims made against us and could have high deductibles. Defending a suit, regardless of its merit, could be costly and divert management attention. In addition, such insurance may not be available to us in the future on economically reasonable terms, or at all. Our use of emerging technologies, including artificial intelligence, may introduce operational, legal and reputational risks. We and our third-party vendors may use emerging technologies, including artificial intelligence and machine-learning tools, in connection with research, data analysis, clinical operations or other business processes. These technologies may produce inaccurate, incomplete or misleading outputs, and errors may not be readily detectable. Their use may also raise novel issues relating to data privacy, intellectual property ownership, regulatory compliance and evolving industry standards. The legal and regulatory framework governing these technologies is rapidly evolving. If we fail to appropriately govern their use, or if regulators impose new restrictions or requirements, we could experience delays, increased costs, regulatory scrutiny, litigation exposure or reputational harm, any of which could materially adversely affect our business. Our business is subject to economic, political, regulatory and other risks associated with conducting business internationally. We may seek regulatory approval or licensure of our product candidate outside of the United States. Accordingly, we expect that we will be subject to additional risks related to operating in foreign countries if we obtain the necessary approvals or licenses, including, but not limited to: • differing regulatory requirements and reimbursement regimes in foreign countries; • unexpected changes in tariffs, trade barriers, price and exchange controls and other regulatory requirements; • economic weakness, including inflation, or political instability in particular foreign economies and markets; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; • challenges enforcing our contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual property rights to the same extent as the U.S.; • production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and • business interruptions resulting from geo-political actions, including war and terrorism. 73 Changes in U.S. or international social, political, regulatory and economic conditions or in laws and policies governing trade, manufacturing, development and investment in the countries where we currently conduct our business could adversely affect our business, reputation, financial condition and results of operations. Changes or proposed changes in U.S. or other countries’ trade policies may result in restrictions and economic disincentives on international trade. The U.S. government has recently imposed, or is currently considering imposing, tariffs on certain trade partners, including China. Tariffs, economic sanctions and other changes in U.S. trade policy have in the past and could in the future trigger retaliatory actions by affected countries, and certain foreign governments have instituted or are considering imposing retaliatory measures on certain U.S. goods. Further, any emerging protectionist or nationalist trends (whether regulatory- or consumer-driven) either in the United States or in other countries could affect the trade environment. Our business, like many other corporations, would be impacted by changes to the trade policies of the United States and foreign countries (including governmental action related to tariffs, international trade agreements, or economic sanctions). Such changes have the potential to adversely impact the U.S. economy or certain sectors thereof, the global economy, and our industry, and as a result, could have a material adverse effect on our business, financial condition and results of operations. Our research and development activities involve hazardous materials, and noncompliance with environmental, health and safety laws could result in significant liability. Our research and development activities, and those of our third-party vendors, may involve the use, storage, transportation and disposal of biological materials, chemicals and other hazardous substances. These activities are subject to extensive environmental, health and safety laws and regulations. Accidental contamination, spills, exposures or other incidents could occur. If such events occur, we could incur significant costs for investigation, remediation, fines or penalties, third-party claims and reputational harm. In addition, any material failure to comply with applicable environmental, health and safety requirements could disrupt our operations or delay development activities, which could materially adversely affect our business and prospects. Disruptions at the FDA, the SEC and other government agencies could hinder their ability to perform normal business functions on which the operation of our business may rely, which could negatively impact our business. The ability of the FDA to review and approve new products can be affected by a variety of factors, including government funding, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory and policy changes. Average review times at the agency have fluctuated in recent years as a result. In addition, government funding of the U.S. Securities and Exchange Commission (SEC), and other government agencies on which our operations may rely, including those that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable. Disruptions at the FDA and other agencies may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. For example, in recent years, including in October 2025, the U.S. government shut down several times and certain regulatory agencies, such as the FDA and the SEC, had to furlough critical employees and stop critical activities. If a prolonged government shutdown were to occur, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business. Further, future government shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations. If a prolonged government shutdown occurs, or if global health concerns prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business. 74 Risks Related to Our Dependence on Third Parties If we fail to comply with our obligations under any license, collaboration or other agreements, we may be required to pay damages and could lose intellectual property rights that are necessary for developing and protecting our product candidate or we could lose certain rights to grant sublicenses. We are a party to license agreements with Pfizer, Biosion, and the University of Chicago, pursuant to which we in-license patents and technology for certain of our product candidate, pursuant to which we may license patents and technology for future product candidate. Our current license agreements and our collaboration agreement impose, and any future license agreements or collaboration agreements we enter into are likely to impose, various development, commercialization, funding, milestone, royalty, diligence, sublicensing, insurance, patent prosecution and enforcement and/or other obligations on us. If we breach any of these obligations, or use the intellectual property licensed to us in an unauthorized manner, we may be required to pay damages and the licensor may have the right to terminate the license, which could result in us being unable to develop, manufacture and sell products that are covered by the licensed technology or enable a competitor to gain access to the licensed technology. Moreover, our licensors may own or control intellectual property that has not been licensed to us and, as a result, we may be subject to claims, regardless of their merit, that we are infringing or otherwise violating the licensor’s rights. In addition, while we cannot currently determine the amount of the royalty obligations we would be required to pay on sales of future products, if any, the amounts may be significant. The amount of our future royalty obligations will depend on the technology and intellectual property we use in products that we successfully develop and commercialize, if any. Therefore, even if we successfully develop and commercialize products, we may be unable to achieve or maintain profitability. We may form or seek additional collaborations or strategic alliances or enter into additional licensing arrangements in the future. If any of these collaborations, strategic alliances or licensing arrangements are not successful, we may not be able to capitalize on the market potential of the product candidate. We may in the future form or seek strategic alliances, create joint ventures or collaborations or enter into additional licensing arrangements with third parties that we believe will complement or augment our development and commercialization efforts with respect to our current or future product candidate. Any of these relationships may require us to incur non-recurring and other charges, increase our near and long-term expenditures, issue securities that dilute our existing stockholders or disrupt our management and business. We face significant competition in seeking appropriate strategic partners, and the negotiation process for these sorts of transactions is time-consuming, complex and expensive. Moreover, we may not be successful in our efforts to establish a strategic partnership or other alternative arrangements for our product candidate because they may be deemed to be at too early of a stage of development for collaborative effort and third parties may not view our product candidate as having the requisite potential to demonstrate safety, potency, purity and efficacy and obtain marketing approval. Additionally, our existing partners may decide to acquire or partner with other companies developing oncology therapeutics, which may have an adverse impact on our business prospects, financial condition and results of operations. Further, if we enter into additional collaboration agreements and strategic partnerships or license our product candidate, we may not be able to realize the benefit of those transactions if we are unable to successfully integrate them with our existing operations and company culture, which could delay our timelines or otherwise adversely affect our business prospects, financial condition and results of operations. We also cannot be certain that, following a strategic transaction or license, we will achieve the revenue or specific net income that justifies the entry into the transaction in the first place. Any delays in entering into new collaborations or strategic partnership agreements related to our product candidate could delay the development and commercialization of our product candidate in certain geographies for certain indications, which would harm our business prospects, financial condition and results of operations. We rely on third parties to manufacture our product candidate. Any failure by a third party manufacturer to produce acceptable raw materials or product candidate for us or to obtain authorization from the FDA or comparable foreign regulatory authorities relating thereto may delay or impair our ability to initiate or complete our clinical trials, obtain regulatory licensure or approvals or commercialize approved products. We do not currently have, nor do we plan to acquire, the infrastructure or capability to manufacture or distribute preclinical, clinical or commercial quantities of drug substance or drug product, including our existing product candidate. We rely on third party contract manufacturers to manufacture our preclinical and clinical trial product supplies. We expect to continue to rely on third party manufacturers if we receive regulatory licensure for our product candidate. We do not have complete control over the ability of our third party manufacturers to maintain adequate manufacturing capacity and capabilities to serve our needs, including quality control, quality assurance and qualified personnel. There can be no assurance that our preclinical and clinical development product supplies will not be limited, interrupted, or of satisfactory quality or continue to be available at acceptable prices, whether as a result of inflationary pressures or otherwise. In particular, any replacement of any of our manufacturers could require significant effort and expense because there may be a limited number of qualified replacements and could take a significant amount of time to complete. 75 The manufacturing process for a product candidate is subject to FDA and foreign regulatory authority review. Suppliers and manufacturers must meet applicable manufacturing requirements and undergo rigorous facility and process validation tests required by regulatory authorities in order to comply with regulatory standards, such as Current Good Manufacturing Practice (cGMP). In the event that any of our manufacturers fail to comply with such requirements or to perform its obligations to us in relation to quality, timing or otherwise, or if our supply of components or other materials becomes limited or interrupted for other reasons, we may be forced to manufacture the materials ourselves, for which we currently do not have the capabilities or resources, or enter into an agreement with another third party, which we may not be able to do on reasonable terms, if at all. In some cases, the technical skills or technology required to manufacture our product candidate may be unique or proprietary to the original manufacturer and we may have difficulty transferring such skills or technology to another third party and a feasible alternative may not exist. These factors would increase our reliance on such manufacturer or require us to obtain a license from such manufacturer in order to have another third party manufacture our product candidate. If we are required to change manufacturers for any reason, we will be required to verify that the new manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations and guidelines. The delays associated with the verification of a new manufacturer could negatively affect our ability to develop our product candidate in a timely manner or within budget. We expect to continue to rely on third party manufacturers if we receive regulatory licensure for our product candidate. To the extent that we have existing, or enter into future, manufacturing arrangements with third parties, we will depend on these third parties to perform their obligations in a timely manner consistent with contractual and regulatory requirements, including those related to quality control and assurance. If we are unable to obtain or maintain third party manufacturing for our product candidate, or to do so on commercially reasonable terms, we may not be able to develop and commercialize our product candidate successfully. Our or a third party’s failure to execute on our manufacturing requirements and comply with cGMP or similar foreign requirements could adversely affect our business in a number of ways, including: • an inability to initiate or continue clinical trials of the product candidate under development; • delay in submitting regulatory applications, or receiving regulatory licenses, for the product candidate; • loss of the cooperation of an existing or future collaborator; • subjecting third party manufacturing facilities or our manufacturing facilities to additional inspections by regulatory authorities; • requirements to cease distribution or to recall batches of our product candidate; and • the inability to commercialize a product candidate, and an inability to meet commercial demands for such products. We may be unable to establish agreements with third party CDMOs, or to do so on acceptable terms. Even if we are able to establish agreements with CDMOs, reliance on them entails additional risks, including: • reliance on the CDMO for regulatory, compliance and quality assurance; • the possible breach of the manufacturing agreement by the CDMO; • the possible misappropriation of our proprietary information, including our trade secrets and know-how; and • the possible termination or non-renewal of the agreement by the CDMO at a time that is costly or inconvenient for us. We have only limited technology transfer agreements in place with respect to our product candidate, and these arrangements do not extend to commercial supply and, in some instances, to clinical supply. We acquire many key materials on a purchase order basis. As a result, we do not have long-term committed arrangements with respect to our product candidate and other materials. If we receive marketing licensure for our product candidate, we will need to establish an agreement for commercial manufacture with a third party. The CDMOs we retain may not be able to comply with cGMP regulations or comparable foreign regulatory requirements. Our failure, or the failure of our CDMOs, to comply with applicable regulations could result in sanctions being imposed on us, including clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of license, license revocation, seizures or recalls of our product candidate or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our products. 76 The facilities used by our contract manufacturers to manufacture our product candidate must be approved by the FDA or the EU Member States in coordination with the EMA pursuant to inspections that will be conducted after we submit our BLA to the FDA or our marketing authorization application to the EMA. We do not have complete control over all aspects of the manufacturing process of, and are dependent on, our contract manufacturing partners for compliance with cGMP regulations for manufacturing. Third party manufacturers may not be able to comply with cGMP regulations or comparable foreign regulatory requirements. If our contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or comparable foreign regulatory bodies, they will not be able to secure and/or maintain marketing licensure for their manufacturing facilities. In addition, we do not have complete control over the ability of our contract manufacturers to maintain adequate quality control, quality assurance and qualified personnel. If the FDA, EU Member States and the EMA or other comparable regulatory authorities do not approve these facilities for the manufacture of our product candidate or if they withdraw any such licensure in the future, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain marketing licensure for or market our product candidate, if approved or licensed. Our failure, or the failure of our third party manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including fines, injunctions, civil penalties, delays, suspension or withdrawal of licensure, license revocation, seizures or recalls of products or our product candidate, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our product candidate and harm our business and results of operations. Our product candidate and any products that we may develop may compete with other product candidates and products for access to suitable manufacturing facilities. As a result, we may not obtain access to these facilities on a priority basis or at all. There are a limited number of manufacturers that operate under cGMP regulations and that might be capable of manufacturing for us. Any performance failure on the part of our existing or future manufacturers could delay clinical development or marketing licensure. We do not currently have arrangements in place for redundant supply or a second source for bulk drug substance. If our current CDMOs cannot perform as agreed, we may be required to replace such manufacturers. Although we believe that there are several potential alternative manufacturers who could manufacture our product candidate, we may incur added costs and delays in identifying and qualifying any such replacement manufacturer or be able to reach agreement with any alternative manufacturer. Our current and anticipated future dependence upon others for the manufacture of our product candidate or products may adversely affect our future profit margins and our ability to commercialize any products that receive marketing licensure on a timely and competitive basis. Legislative or regulatory restrictions on the use of certain foreign biotechnology or manufacturing service providers could materially disrupt our operations. We rely on third-party manufacturers, suppliers and service providers for the development, manufacture and supply of our product candidate and related materials. Some of these third parties, or their subcontractors, may be located outside the United States. From time to time, legislative or regulatory proposals are introduced that could restrict, condition or prohibit U.S. companies from contracting with, or sourcing from, certain foreign biotechnology or manufacturing service providers, including providers located in China. If such restrictions are enacted or expanded, we or our vendors may be required to discontinue relationships with affected counterparties, even if those counterparties provide specialized capabilities, capacity, or cost advantages. Transitioning to alternative providers could require significant time and expense, including technology transfer, qualification and validation activities, additional audits, and potential regulatory engagement. We may be unable to identify acceptable alternatives on reasonable timelines or terms, which could delay clinical trials, interrupt manufacturing, increase development costs, and materially adversely affect our business and prospects. 77 A portion of our manufacturing of our product candidate takes place in China, through third party manufacturers. A significant disruption in the operation of those manufacturers could materially adversely affect our business, financial condition and results of operations. We currently contract manufacturing operations to third parties, and large quantities of our product candidate is manufactured by these third parties globally, including in China. Any disruption in production or inability of our manufacturers to produce adequate quantities to meet our needs could impair our ability to operate our business on a day-to-day basis and to continue our development of our product candidate. Foreign and certain Chinese biotechnology companies and CDMOs, may become subject to U.S. legislation, including the legislation pending in Congress called the BIOSECURE Act. The Act could impose trade restrictions, sanctions, and other regulatory requirements by the U.S. government, which could restrict or even prohibit our ability to work with such entities. If we are restricted or prohibited from working with our current CDMOs, we may incur added costs or reduction of the supply of material available to us, delays in the procurement or supply of such material or adverse effects on our ability to manufacture our product candidate. Additionally, changes in U.S. trade policy, sanctions, export controls, import restrictions, tariffs, or other measures targeting certain foreign jurisdictions or entities could increase our costs, delay clinical supply, limit access to manufacturing capacity or materials, or require us to transition to alternative vendors, which could require significant time, expense, and regulatory effort. Any such disruptions could accelerate our cash burn and increase our need for additional capital. Any of these matters could materially and adversely affect our business and results of operations. Any recall of the manufacturing lots or similar action regarding our product candidate used in clinical trials could delay the trials or detract from the integrity of the trial data and its potential use in future regulatory filings. . In addition, supply chain disruptions and delays may also occur as a result of any new tariff policies or trade restrictions, which could also negatively impact third party manufacturing. For example, on April 2, 2025, the United States government announced a baseline 10% tariff on all foreign goods, with goods imported from specified nations, including China and those in the European Union, taxed at higher rates. Any of these matters could materially and adversely affect our business and results of operations. Recent U.S. biosecurity-related legislation and related regulatory actions could restrict or complicate the ability of life sciences companies to use certain third-party biotechnology service providers, including for manufacturing, testing, or research services, particularly where federal funding, grants, or contracts are implicated. To the extent we or our collaborators rely on affected providers (including providers with operations in China), we may need to transition to alternative vendors, which could increase costs, delay development timelines, and disrupt supply chains. Our CDMOs may be unable to successfully scale-up manufacturing of our product candidate in sufficient quality and quantity, which would delay or prevent us from developing our product candidate and commercializing approved products, if any. In order to conduct clinical trials of our product candidate, we will need to manufacture it in large quantities. Quality issues may arise during scale-up activities. Our reliance on a limited number of CDMOs, the complexity of drug manufacturing and the difficulty of scaling up a manufacturing process could cause the delay of clinical trials, regulatory submissions, required licensure, or commercialization of our product candidate, cause us to incur higher costs and prevent us from commercializing our product candidate successfully. Furthermore, if our CDMOs fail to deliver the required commercial quality and quantities of materials on a timely basis and at commercially reasonable prices, and we are unable to secure one or more replacement CDMOs capable of production in a timely manner at a substantially equivalent cost, then testing and clinical trials of our product candidate may be delayed or infeasible, and regulatory licensure or commercial launch of any resulting product may be delayed or not obtained, which could significantly harm our business. If we are unable to obtain sufficient raw and intermediate materials on a timely basis or if we experience other manufacturing or supply difficulties, our business may be adversely affected. The manufacture of our product candidate requires the timely delivery of sufficient amounts of raw and intermediate materials. We work closely with our suppliers to ensure the continuity of supply but cannot guarantee these efforts will always be successful. Further, while efforts are made to diversify our sources of raw and intermediate materials, in certain instances we acquire raw and intermediate materials from a sole supplier. While we believe that alternative sources of supply exist where we rely on sole supplier relationships, there can be no assurance that we will be able to quickly establish additional or replacement sources for some materials. A reduction or interruption in supply, and an inability to develop alternative sources for such supply, could adversely affect our ability to manufacture our product candidate in a timely or cost-effective manner. We expect to rely on third parties to conduct our clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines for completing such trials. We will rely on third party CROs to conduct clinical trials for our biological product candidate. We currently do not plan to conduct any clinical trials independently. Agreements with these CROs might terminate for a variety of reasons, including for their failure to perform. Entry into alternative arrangements, if necessary, could significantly delay our product development activities. 78 Our reliance on these CROs for research and development activities will reduce our control over these activities but will not relieve us of our responsibilities. For example, we will remain responsible for ensuring that each of our clinical trials is conducted in accordance with the general investigational plan and protocols in the applicable IND. Moreover, the FDA requires compliance with standards, commonly referred to as GCPs for conducting, recording and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial participants are protected. If these CROs do not successfully carry out their contractual duties, meet expected deadlines or conduct our clinical trials in accordance with regulatory requirements or our stated protocols, we will not be able to obtain, or may be delayed in obtaining, marketing licenses for our product candidate and will not be able to, or may be delayed in our efforts to, successfully commercialize our product candidate. Risks Related to Our Intellectual Property If we are unable to obtain or protect our intellectual property in and to our product candidate, we may not be able to compete effectively in our markets. We rely upon a combination of patents, proprietary know-how, trade secret protection and confidentiality agreements to protect the intellectual property related to our product candidate and discovery programs. Our success depends in large part on our ability to obtain and maintain patent and other intellectual property rights in the U.S. and other countries. We and or licensors have filed patent applications in the U.S. and abroad directed to our product candidate in an effort to establish intellectual property positions for their compositions of matter as well as uses in the treatment of diseases. Our intellectual property includes patents and patent applications that we own, as well as those we in-license, including in-licensed patents that we manage directly and those that remain managed by our licensors. We or our licensors have not pursued or maintained, and may not pursue or maintain in the future, patent protection for our product candidate in every country or territory in which we may sell our products, if approved. The patent prosecution process is expensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. In addition, we cannot be sure that any of our pending patent applications will issue, or that if issued, will be in a form advantageous to us. The United States Patent and Trademark Office (USPTO), international patent offices, or judicial bodies may deny, or significantly narrow claims made under our patent applications and our patents may be successfully challenged, may be designed around, or may otherwise be of insufficient scope to provide us with protection for our commercial products. It is possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection. We may be subject to a third party submission of prior art to the USPTO, or other patent offices, in our pending patent applications. There is no assurance that all of the potentially relevant prior art relating to our patents and patent applications has been found, which can invalidate a patent or prevent a patent from issuing. In addition to the above, patent prosecution is a lengthy process, during which the scope of the claims initially submitted for examination by the USPTO may be significantly narrowed or may not issue at all. The claims of our issued patents or patent applications when issued may not cover our current or future product candidate, or even if such patents provide coverage, the coverage obtained may not provide any competitive advantage. The patent applications that we own, or in-license, may fail to result in issued patents with claims that cover our current or future product candidate in the U.S. or in other foreign countries, or we may be required to disclaim all or a portion of the remaining patent term to secure issuance. Even if patents do successfully issue, third parties may challenge their validity, enforceability or scope, which may result in such patents being narrowed, invalidated, or held unenforceable. Any successful opposition to these patents or any other patents owned by or licensed to us could deprive us of rights necessary for the successful commercialization of current and future product candidate. Further, if we encounter delays in regulatory licensure or approvals, the period of time during which we could market a product candidate under patent protection could be reduced. If the patent applications we own or have in-licensed with respect to our product candidate and discovery programs fail to issue, if their breadth or strength of protection is threatened, or if they fail to provide meaningful exclusivity for our current or any future product candidate, it could dissuade companies from collaborating with us to develop and commercialize product candidate and future drugs and threaten our ability to commercialize future drugs. Any such outcome could have a negative effect on our business. 79 The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation. In addition, the laws of foreign countries may not protect our intellectual property rights to the same extent as the laws of the U.S. For example, European patent law restricts the patentability of methods of treatment of the human body more than U.S. law does. Furthermore, other parties may have developed or may develop technologies that may be related to, or competitive with, our technologies, and such parties may have filed, or may file, patent applications, or may have received, or may receive, patents, claiming inventions that may overlap or conflict with those claimed in our patent applications or issued patents, and that we may rely upon to establish exclusivity for our products in the market. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the U.S. and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all. Therefore, we cannot know with certainty whether we were the first to make the inventions claimed in our owned or licensed patents or pending patent applications, or that we were the first to file for patent protection of such inventions. It is also possible that in our evaluation of third party intellectual property, we failed to identify relevant patents or applications. We cannot guarantee that any of our patent searches or analyses, including but not limited to the identification of relevant patents, the scope of patent claims or the expiration of relevant patents, are complete or thorough, nor can we be certain that we have identified each and every third party patent and pending application in the U.S. and abroad that is relevant to or necessary for the commercialization of our current and future products. As a result, the issuance, scope, validity, enforceability and commercial value of our patent rights are highly uncertain. Our pending and future patent applications may not result in patents being issued which protect our technology or drugs, in whole or in part, or which effectively prevent others from commercializing competitive technologies and drugs. Changes in either the patent laws or interpretation of the patent laws in the U.S. and other countries may diminish the value of our patents or narrow the scope of our patent protection. The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and licensed patent rights may be challenged in the courts or patent offices in the U.S. and abroad. For example, we may become involved in opposition, derivation, reexamination, inter partes review, post-grant review, or interference proceedings challenging our patent rights or the patent rights of others. An adverse determination in any such proceeding, or in litigation, could reduce the scope of our patent claims, result in our patent rights being held invalid, in whole or in part, or unenforceable, or limit the duration of the patent protection of our technology and products, and allow third parties to commercialize our technology or products and compete directly with us without payment to us, or result in our inability to manufacture or commercialize products without infringing third party patent rights. In addition, if the breadth or strength of protection provided by our patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize our current or any future product candidate. Moreover, patents have a limited lifespan. In the U.S. and internationally, a patent generally expires 20 years after the earliest filing date of a non-provisional patent application. Various extensions may or may not be available; however, the life of a patent, and the protection it affords, is limited. Without patent protection for our current or future product candidate, we may be open to competition from generic and/or biosimilar versions of such products. Given the amount of time required for the development, testing and regulatory review of new product candidate, patents protecting such candidate might expire before or shortly after such candidates are commercialized. As a result, our owned and licensed patent rights may not provide us with sufficient rights to exclude others from commercializing drugs similar or identical to ours. We may also rely on trade secrets, know-how and continuing technological innovation to develop and maintain our proprietary and intellectual property position. Even if our patent rights are unchallenged, our issued patents and our pending patent applications, if issued, may not provide us with any meaningful protection or prevent competitors from designing around our patent claims to circumvent our owned patent rights by developing similar or alternative technologies or products in a non-infringing manner. For example, a third party may develop a competitive product that provides benefits similar to one or more of our product candidates, but that has a different composition that falls outside the scope of our patent protection. If the protection provided by our patent rights with respect to our product candidates is not sufficiently broad to impede such competition, or if the breadth, strength or term (including any extensions or adjustments) of protection provided by our patent rights with respect to our product candidates or any future product candidates is successfully challenged, our ability to successfully commercialize our product candidate could be negatively affected, which would harm our business. 80 Obtaining and maintaining our patent rights depends on compliance with various procedural, document submission, fee payment and other requirements imposed by government patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements. The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. In addition, periodic maintenance fees, renewal fees, annuity fees and various other government fees on patents and/or patent applications will have to be paid to the USPTO and various government patent agencies outside of the U.S. over the lifetime of our owned and licensed patents and/or applications and any patent rights we may own or license in the future. We rely on a combination of in-house employees, reputable law firms, service providers, and our licensors to pay these fees and to help us comply with these requirements. Non-compliance events that could result in abandonment or lapse of a patent or patent application include, but are not limited to, failure to respond to official actions within prescribed time limits, non-payment of fees, and failure to properly legalize and submit formal documents. If we or our licensors fail to maintain the patents and patent applications covering our products or technologies, we may not be able to stop a competitor from marketing products that are the same as, or similar to, our product candidates, which would have a material adverse effect on our business. In many cases, an inadvertent lapse can be cured by payment of a late fee or by other means in accordance with the applicable rules. There are situations, however, in which non-compliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. In such an event, potential competitors might be able to enter the market and this circumstance could harm our business. In addition, if we fail to apply for, or are unsuccessful in our application for, applicable patent term extensions or adjustments, we will have a more limited time during which we can enforce our granted patent rights. In addition, if we are responsible for patent prosecution and maintenance of patent rights in-licensed to us, any of the foregoing could expose us to liability to the applicable patent owner. Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could have a negative impact on the success of our business. Third parties may initiate legal proceedings against us or our licensors or collaborators alleging that we or our licensors or collaborators are infringing their intellectual property rights or to challenge the validity or scope of our intellectual property rights, including in oppositions, interferences, reexaminations, inter partes reviews, derivation or other similar proceedings before the U.S. or other domestic or foreign jurisdictions. These proceedings can be expensive and time-consuming and adversaries in these proceedings may have the ability to dedicate substantially greater resources to prosecuting these legal actions than we or our licensors or collaborators can. An unfavorable outcome could require us or our licensors or collaborators to cease using the related technology or developing or commercializing our product candidates, or to attempt to license rights to it from the prevailing party. Our business could be harmed if the prevailing party does not offer us or our licensors or collaborators a license on commercially reasonable terms or at all. Even if we or our licensors or collaborators obtain a license, it may be non-exclusive, thereby giving our competitors access to the same technologies licensed to us or our licensors or collaborators. In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees. A finding of infringement could prevent us from commercializing our product candidates or force us to cease some of our business operations, which could materially harm our business. We may be subject to claims asserting that our employees, consultants or advisors have wrongfully used or disclosed alleged trade secrets of their current or former employers or claims asserting ownership of what we regard as our own intellectual property. Many of our employees, consultants or advisors were previously, or are currently, employed at universities or other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Although we try to ensure that our employees, consultants and advisors do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that these individuals have used or disclosed confidential information or intellectual property, including trade secrets, or other proprietary information of any such individual’s current or former employer. Litigation may be necessary to defend against these claims. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. Even if we are successful in defending against such claims, litigation could result in substantial costs and distract management. We may in the future be subject to claims by our former employees or consultants asserting an ownership right in our patents, or patent applications, as a result of the work they performed on our behalf. Although it is our policy to require our employees and contractors who may be involved in the conception or development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who, in fact, conceives or develops intellectual property that we regard as our own, and we cannot be certain that our agreements with such parties will be upheld in the face of a potential challenge or that they will not be breached, for which we may not have an adequate remedy. The assignment of intellectual property rights may not be self-executing, or the assignment agreements may be breached, and we may be forced to bring claims against third parties, or defend claims that they may bring against us, to determine the ownership of what we regard as our intellectual property. 81 Licensing of intellectual property is of critical importance to our business and involves complex legal, business and scientific issues. If we breach our Pfizer license agreement or any of the other agreements under which we acquired, or will acquire, intellectual property rights covering our product candidates, we could lose the ability to continue the development and commercialization of the related product candidates(s). The licensing of intellectual property is of critical importance to our business and to our current and future product candidates, and we may enter into additional such agreements in the future. In particular, the rights to the intellectual property covering MICVO are in-licensed from Pfizer. If we fail to meet our obligations under any of our in-license agreements, including the amended and restated license agreement with Pfizer, dated October 6, 2022, as further amended, then the licensor may terminate the license agreement. If one of our material in-license agreements is terminated, we will lose the right to continue to develop and commercialize the product candidate(s) covered by such in-license agreement. While we would expect to exercise all rights and remedies available to us, including seeking to cure any breach by us, and otherwise seek to preserve our rights under our in-license agreements, we may not be able to do so in a timely manner, at an acceptable cost or at all. We may become involved in lawsuits to protect or enforce our patents, the patents of our licensors or our other intellectual property rights, which could be expensive, time-consuming and unsuccessful. Competitors may infringe or otherwise violate our patents, the patents of our licensors or our other intellectual property rights. To counter infringement or unauthorized use, we may be required to file legal claims, which can be expensive and time-consuming and is likely to divert significant resources from our core business, including distracting our technical and management personnel from their normal responsibilities. In addition, in an infringement proceeding, a court may decide that a patent of ours or our licensors is not valid, is unenforceable, or may refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question. An adverse result in such proceedings could put one or more of our owned or licensed patents at risk of being invalidated or interpreted narrowly and could put our owned or licensed patent applications at risk of not issuing. The initiation of a claim against a third party might also cause the third party to bring counter claims against us, such as claims asserting that our patent rights are invalid or unenforceable. In patent litigation in the U.S., defendant counterclaims alleging invalidity or unenforceability are commonplace. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, non-enablement or lack of statutory subject matter. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent, withheld relevant material information from the USPTO, or made a materially misleading statement, during prosecution. Third parties may also raise similar validity claims before the USPTO in post-grant proceedings such as ex party reexaminations, inter parties review, or post-grant review, or oppositions or similar proceedings outside the U.S., in parallel with litigation or even outside the context of litigation. The outcome following legal assertions of invalidity and unenforceability is unpredictable. We cannot be certain that there is or will be no invalidating prior art, of which we and the patent examiner were unaware during prosecution. For the patents and patent applications that we have licensed, we may have limited or no right to participate in the defense of any licensed patents against challenge by a third party. If a defendant were to prevail on a legal assertion of invalidity or unenforceability, we would lose at least part, and perhaps all, of any future patent protection on our current or future product candidates. Such a loss of patent protection could harm our business. We may not be able to prevent, alone or with our licensors, misappropriation of our intellectual property rights, particularly in countries where the laws may not protect those rights as fully as in the U.S. Any litigation or other proceedings to enforce our intellectual property rights may fail, and even if successful, may result in substantial costs and distract our management and other employees. Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation. There could also be public announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have an adverse effect on the price of our common stock. We may not have sufficient financial or other resources to adequately conduct such litigation or proceedings. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources and more mature and developed intellectual property portfolios. Accordingly, despite our efforts, we may not be able to prevent third parties from infringing upon or misappropriating or from successfully challenging our intellectual property rights. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could have a material adverse effect on our ability to compete in the marketplace. 82 Changes in U.S. patent law or the patent law of other countries or jurisdictions could diminish the value