Aktis Oncology, Inc. 10-K

10-K 1 aktis_12.31.25_10k.htm 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: 001-43047 Aktis Oncology, Inc. (Exact name of Registrant as specified in its Charter) Delaware 85-2584233 (State or other jurisdiction of incorporation or organization) (I.R.S. Employer Identification No.) 17 Drydock Avenue, Suite 17-401 Boston, Massachusetts 02210 (Address of principal executive offices) (Zip Code) Registrant’s telephone number, including area code: (617) 461-4023 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 $0.0001 per share AKTS The Nasdaq Stock Market LLC 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 report. ☐ If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐ Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐ Indicate by check mark whether the Registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). YES ☐ NO ☒ The Registrant did not have a public float on the last business day of its most recently completed second fiscal quarter because there was no public market for the Registrant’s common equity as of such date. The number of shares of Registrant’s Common Stock and Class A common stock outstanding as of March 10, 2026 was 53,403,173 and 1,872,829, respectively. DOCUMENTS INCORPORATED BY REFERENCE None. SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS This Annual Report on Form 10-K contains forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements are neither historical facts nor assurances of future performance. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “estimate,” “believe,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions intended to identify statements about the future, although not all forward-looking statements contain these identifying words. These forward-looking statements include, without limitation, statements about the following: • the timing, scope, progress and results of our research and development programs, preclinical studies, clinical trials, investigational new drug or biological license applications, and other regulatory submissions; • the timing of, and costs involved in, obtaining and maintaining regulatory approval of [ 225 Ac]Ac-AKY-1189 for Nectin-4 expressing tumors, [ 225 Ac]Ac-AKY-2519 for B7-H3 expressing tumors and any other current or future product candidates that we may identify or develop; • our ability to obtain an adequate supply at reasonable costs of 225 Ac or any other radioisotope we may incorporate into our drug candidates; • our ability to address the fulfillment and logistical challenges posed by the time-limited stabilization of [ 225 Ac]Ac-AKY-1189 for UC and other Nectin-4 expressing tumors or any other current or future product candidate we develop; • our ability to obtain funding for our operations necessary to complete the clinical trials for [ 225 Ac]Ac-AKY-1189 for Nectin-4 expressing tumors, our other product candidates, or any future product candidates; • our ability to identify patients with the diseases treated by our product candidates, and to enroll patients in trials; • our expectations regarding the size of the patient populations, market acceptance and opportunity for and clinical utility of our product candidates, if approved for commercial use; • our ability to advance our miniprotein radioconjugate platform; • our ability to maintain existing, and establish new, strategic collaborations, licensing or other arrangements, including our ability to comply with our financial obligations pursuant to the terms of such agreements; • the timing and likelihood of the achievement of milestones pursuant to our existing collaboration and licensing agreements; • our ability to identify and develop product candidates for treatment of additional indications; • our commercialization, marketing and manufacturing capabilities and strategy, including the timing and costs of constructing our own current Good Manufacturing Practices facility; • the performance of our third-party service providers, including our suppliers and manufacturers; • the rate and degree of market acceptance and clinical utility for, [ 225 Ac]Ac-AKY-1189 for UC and any other Nectin-4 expressing tumors, and any other current or future product candidates we may develop; • the effects of competition with respect to [ 225 Ac]Ac-AKY-1189, any other current or future product candidates, as well as innovations by current and future competitors in our industry; • the implementation of our strategic plans for our business, any product candidates we may develop; • our estimates regarding the market opportunities for our drug candidates; • our intellectual property position, including the scope of protection we are able to establish, maintain, defend, protect and enforce for intellectual property rights covering our product candidates; • our ability to attract and retain key scientific or management personnel; • regulatory and legal developments in the United States and foreign countries; • our expectations regarding the period during which we qualify as an emerging growth company and smaller reporting Company under the Jumpstart Our Business Startups Act of 2012, as amended; • business disruptions affecting the initiation, patient enrollment, development and operation of our clinical trials, including a public health emergency, such as the recent global COVID-19 pandemic; • the accuracy of our estimates regarding future expenses, future revenue, capital requirements and need for additional financing; and • our financial performance and our ability to effectively manage our anticipated growth. We have based these forward-looking statements largely on our current expectations and projections about our business, the industry in which we operate and financial trends that we believe may affect our business, financial condition, results of operations and prospects, and these forward-looking statements are not guarantees of future performance or development. 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. 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. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein for any reason after the date of this report to conform these statements to new information, future events or otherwise. You should read this Annual Report on Form 10-K and the documents that we reference herein and have filed with the SEC as exhibits to this Annual Report on Form 10-K with the understanding that our actual future results, levels of activity, performance and events and circumstances may be materially different from what we expect. SUMMARY RISK FACTORS The risk factors summarized and detailed below could materially harm our business, operating results and/or financial condition, impair our future prospects and/or cause the price of our common stock to decline. These are not all of the risks we face, and other factors not presently known to us or that we currently believe are immaterial may also affect our business if they occur. A summary of the material risks that may affect our business, operating results and financial condition include, but are not necessarily limited to, those relating to: • We have incurred significant losses since our inception, have no products approved for sale, and we expect to incur losses for the foreseeable future. • Our limited operating history may make it difficult for you to evaluate our prospects and likelihood of success. • We will require additional funding to finance operations. If we are unable to raise capital when needed, or on acceptable terms, we would be forced to delay, reduce, or eliminate our research and product candidate development programs. • We are early in our development efforts. If we are unable to develop, and commercialize, any of our current or future product candidates through clinical development, obtain regulatory approval and ultimately commercialize our product candidates, or if we experience significant delays in doing so, our business will be materially harmed. • Our business is highly dependent on our lead product candidate, [ 225 Ac]Ac-AKY-1189, for the treatment of Nectin-4 expressing tumors. We must complete clinical trials before we can seek regulatory approval and begin commercialization of [ 225 Ac]Ac-AKY-1189. If we are unable to obtain regulatory approval for, and successfully commercialize, [ 225 Ac]Ac-AKY-1189, our business may be materially harmed, and such failure may affect our other current or future product candidates. • Preclinical and clinical development is a lengthy and expensive process with uncertain timelines and uncertain outcomes. If preclinical studies or clinical trials of a product candidate are prolonged or delayed, we may be unable to obtain required regulatory approvals, and therefore be unable to commercialize [ 225 Ac]Ac-AKY-1189 for any indication or any of our other current or future product candidates on a timely basis or at all. • Our approach to the discovery and development of product candidates using our miniprotein radioconjugate platform represents a novel approach to radiation therapy, which may create significant and potentially unpredictable challenges for us. • Our product candidates may cause adverse events, undesirable side effects or have other properties that could halt their preclinical or clinical development, prevent, delay, or cause the withdrawal of their regulatory approval, limit their commercial potential, or result in significant negative consequences, including death of patients. • Results of preclinical studies, dosimetry assessments, and early-stage clinical trials may not be predictive of the results of future preclinical studies or clinical trials. • Interim, topline, or preliminary data from our preclinical studies and clinical trials that we announce or publish from time to time may change as more patient data becomes available or as we make changes to our manufacturing processes and are subject to audit and verification procedures that could result in material changes in the final data. • The commercial success of [ 225 Ac]Ac-AKY-1189, or any of our other current or future products, if approved, will depend upon public perception of radiopharmaceuticals and the degree of their market acceptance by physicians, patients, healthcare payors and others in the medical community. Even if [ 225 Ac]Ac-AKY-1189, or any other product candidates we develop receive marketing approval by the FDA or other foreign regulatory authority, they may not achieve the level of commercial acceptance and sales experienced by approved beta-emitting therapies, Pluvicto and Lutathera. • We face substantial competition, which may result in others discovering, developing, or commercializing products before or more successfully than we do. • The development and commercialization of pharmaceutical products is subject to extensive regulation, and the regulatory approval processes of the FDA and comparable foreign authorities are lengthy, time-consuming, and inherently unpredictable. If we are ultimately unable to obtain regulatory approval for [ 225 Ac]Ac-AKY-1189 or our other current or future product candidates, on a timely basis if at all, our business will be substantially harmed. • We intend to build and operate our own manufacturing facility for preclinical and clinical supply needs, which will require significant resources, and we may fail to successfully establish and operate our facility, which could adversely affect our clinical trials and the commercial viability of our product candidates. • Our product candidates are biologics and the manufacture of our product candidates is complex. Even after our planned manufacturing facility is operating, we will continue to rely on third parties to manufacture our product candidates. Our business could be harmed if those third parties fail to provide us with sufficient quantities of product supplies or product candidates, or fail to do so at acceptable quality levels or prices. • We may be unable to obtain a sufficient supply of 225 Ac or other radioisotopes to support clinical development or manufacturing at commercial scale. • We will rely on third parties to conduct our Phase 1b clinical trial of [ 225 Ac]Ac-AKY-1189 and plan to rely on third parties to conduct future clinical trials. If these third parties do not properly and successfully carry out their contractual duties or meet expected deadlines, we may not be able to obtain regulatory approval of or commercialize our product candidates. • We do not own or expect to own any issued patents relating to the radioactive payload, 225 Ac, used in our product candidates, including [ 225 Ac]Ac-AKY-1189 and [ 225 Ac]Ac-AKY-2519. • Our success depends on our ability to obtain, maintain, enforce, defend and protect our intellectual property and our proprietary technologies, and conduct our business without infringing, misappropriating or otherwise violating intellectual property or proprietary rights of others. • Our stock price may be volatile or may decline regardless of our operating performance, resulting in substantial losses for investors. Table of Contents Page PART I Item 1. Business 6 Item 1A. Risk Factors 42 Item 1B. Unresolved Staff Comments 103 Item 1C. Cybersecurity 103 Item 2. Properties 103 Item 3. Legal Proceedings 104 Item 4. Mine Safety Disclosures 181 PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 105 Item 6. [Reserved] 106 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 107 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 118 Item 8. Financial Statements and Supplementary Data F- 1 Item 9. Changes in and Disagreements With Accountants on Accounting and Financial Disclosure 151 Item 9A. Controls and Procedures 151 Item 9B. Other Information 151 Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 151 PART III Item 10. Directors, Executive Officers and Corporate Governance 152 Item 11. Executive Compensation 159 Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters 174 Item 13. Certain Relationships and Related Transactions, and Director Independence 177 Item 14. Principal Accounting Fees and Services 181 PART IV Item 15. Exhibits, Financial Statement Schedules 182 Item 16. Form 10-K Summary 183 Signatures PART I It em 1. Business. Overview We are a clinical-stage oncology company focused on expanding the breakthrough potential of targeted radiopharmaceuticals to large patient populations, including those not addressed by existing platform technologies. The field of targeted radiopharmaceuticals is currently led by two marketed products that illustrated transformative survival outcomes and quality of life benefits can be conferred by delivering radioisotopes to solid tumors. These leading products, which target prostate specific membrane antigen or somatostatin-2 receptor, are each currently approved in only one tumor type, yet have seen considerable commercial uptake and have become fundamental pillars of cancer treatment. Despite these advances, we believe that the field of radiopharmaceuticals is still in its infancy, with many emerging companies still primarily focused on these same two targets. In contrast, we see a significant opportunity to broaden the cancer patient populations benefiting from targeted radiopharmaceuticals by developing next-generation technologies that expand the scope of tumor targets for which it is possible to safely deliver a powerful payload of an alpha-emitting radioisotope. To ensure patient demand is reliably met, we are also establishing efficient end-to-end supply, with a combination of critical internal capabilities paired with established external vendors. Through these efforts, we seek to maximize clinical utility across multiple indications in multiple tumor types, and to expand the commercial uptake of radiopharmaceuticals beyond the traditional nuclear medicine setting and into the more expansive clinical oncology setting. We have built a proprietary miniprotein radioconjugate platform that aims to safely confer breakthrough efficacy to a broad range of patient populations. Our miniprotein radioconjugates are designed to selectively deliver the tumor-killing properties of radioisotopes to targeted tumors with high tumor penetration and prolonged tumor retention, while being rapidly cleared from normal organs and tissues to minimize systemic radiation exposure. Our miniproteins have demonstrated the ability to potently bind to tumor targets outside the scope of current delivery technologies such as peptide-based radioconjugates. We are leveraging the capabilities of our platform technology, together with our expertise and know-how in radiopharmaceutical development, supply chain and manufacturing, to address these challenges with the aim of advancing a deep pipeline of programs against a broad range of tumor targets that have not been successfully targeted with radiopharmaceuticals. Our platform capabilities have generated a pipeline of several novel product candidates. Our most advanced program is a radiopharmaceutical targeting Nectin-4. It is a miniprotein radioconjugate with multi-indication potential across multiple tumor types, in clinical development for the treatment of locally advanced or metastatic urothelial cancer, or UC, and multiple other Nectin-4 expressing solid tumor types. The learnings from the optimization of our Nectin-4 program, the first miniprotein radioconjugate ever advanced into human investigational studies, are being applied to benefit the development of our robust pipeline of several other unpartnered miniprotein radioconjugate programs, which are designed to address other clinically-validated targets. Our lead product candidate, [ 225 Ac]Ac-AKY-1189, contains a miniprotein, AKY-1189, that specifically binds to Nectin-4, and is conjugated via chelation to actinium-225, 225 Ac. 225 Ac, is an alpha-emitting radioisotope that when conjugated to a prostate specific membrane antigen, or PSMA, binding peptide has been shown to confer increased anticancer activity in the post-chemotherapy setting of metastatic castration-resistant prostate cancer compared to an identical PSMA binding peptide with beta-emitting Lutetium-177, or 177 Lu. Nectin-4 is a surface protein found on a wide variety of tumors and has very limited expression in normal adult tissues. Nectin-4 is also the target of Padcev, an antibody-drug conjugate, or ADC, approved worldwide for the treatment of locally advanced or metastatic UC. Padcev has an annualized treatment cost of approximately $500,000 and had worldwide sales of $1.9 billion in 2024, with estimated peak sales of up to $7.0 billion. Despite the commercial success of Padcev, its impact beyond UC has been limited likely due to the need to develop a companion diagnostic for tissue testing when utilizing an ADC. In contrast, we intend to use imaging radioisotopes conjugated to AKY-1189 to select patients most likely to benefit from therapeutic treatment with [ 225 Ac]Ac-AKY-1189. We believe the commercial impact of Padcev validates Nectin-4 as an anticancer target in UC and that significant unmet medical need exists for our lead product candidate in post-Padcev UC. Additionally, we see potential to treat several non-UC Nectin-4-expressing tumor types such as breast cancers and lung cancers. We believe that the therapeutic potential of [ 225 Ac]Ac-AKY-1189 across multiple tumor types is supported by our preclinical studies and data collected by a third-party physician in South Africa pursuant to Section 21 of the Medicines and Related Substances Act, or MRSA, which demonstrated the ability of radiolabeled AKY-1189 to specifically localize to Nectin-4 expressing tumors and rapidly clear from normal organs and tissues. In April 2025, the U.S. Food and Drug Administration, or the FDA, cleared our investigational new drug, or IND, application for [ 225 Ac]Ac-AKY-1189 for the treatment of locally advanced or metastatic UC and other Nectin-4 expressing tumors. We have commenced a multi-site Phase 1b clinical trial in the United States and anticipate preliminary results from the Part-1 dose escalation portion of this trial in the first quarter of 2027. 6 To overcome the manufacturing challenges and supply chain reliability issues that have historically hindered the development and commercialization of radiopharmaceuticals, we are focused on investing in manufacturing and ensuring supply chain continuity and reliability. We have built significant internal capabilities, including subject matter expertise for our product manufacturing processes and a state-of-the-art radiopharmaceutical development suite. Additionally, we have partnered with multiple domestic and international isotope suppliers that provides us priority access to 225 Ac, and with multiple contract manufacturers for the production of our drug product, which collectively are designed to create redundancies across all components of our supply chain. We are also establishing our own current good manufacturing practice, or cGMP, facility to enhance flexibility, increase control, and establish a hybrid internal and external clinical supply chain. We believe our team’s expertise and experience in the development of radiopharmaceuticals will allow us to address the challenges presented by the half-life of radioactive isotopes and establish an efficient supply chain from production to patient administration. We believe that radiopharmaceuticals represent one of the most promising modalities for the treatment of solid tumors. Approved radiopharmaceuticals have demonstrated the ability to overcome the challenges of conventional cancer treatments and provide patients with targeted therapies that have superior efficacy and better tolerability. We believe our approach is validated by, and builds upon, the clinical and commercial success of current radiopharmaceuticals and that our approach has the potential to further transform the cancer treatment paradigm for large patient populations. • Clinical validation of targeted radiopharmaceuticals. Approved beta-emitting radiopharmaceuticals, Pluvicto and Lutathera, have demonstrated statistically significant and clinically meaningful overall survival, progression-free survival and quality of life benefits in global registrational clinical trials. Early-stage clinical trials have also demonstrated that the use of alpha-emitting 225 Ac radioconjugates can deliver more profound anticancer activity than beta-emitting 177 Lu conjugates in similar patient populations, and in patients whose disease has progressed on prior beta-emitting targeted therapies. These promising early clinical data have led to the advancement of 225 Ac-based radioconjugates to pivotal clinical trials, though none yet have filed for approval by the FDA. • Commercial validation of approved radiopharmaceuticals. Pluvicto achieved a first full year of sales of approximately $1 billion, with an annualized treatment cost of approximately $300,000, representing the strongest oncology commercial launch since Ibrance in 2015, which demonstrates the patient impact potential and rapid adoption of radiopharmaceuticals into clinical practice. The estimated global peak sales for Pluvicto are approximately $5.4 billion in prostate cancer alone. The global radiopharmaceuticals market is one of the fastest growing categories among anticancer medicines, and is projected to grow to over $26 billion in sales by 2032. The therapeutic segment of this market is estimated to achieve a total addressable market of $25 billion to $60 billion post-2030. • Strategic validation of radiopharmaceuticals. The commercial success of radiopharmaceuticals, paired with significant increases in investment in innovative approaches, has led to significant value creation through partnering and acquisitions. Aggregate transaction values over the last 10 years are approximately $33 billion. Several large multinational biopharmaceutical oncology leaders have also been significantly investing in radiopharmaceutical operations globally. We believe that the continued capital investment and expansion of operations and the advancement of supply chain capabilities represent recognition of the significant medical and commercial opportunity for radiopharmaceuticals. Our proprietary miniprotein radioconjugate platform We created our proprietary miniprotein radioconjugate platform to build on the successes of currently available radiopharmaceuticals and enable the discovery of next-generation precision radiopharmaceuticals. We are leveraging our platform to discover and develop radiopharmaceutical therapies that selectively deliver the tumor-killing properties of radioisotopes to targeted tumors with high tumor penetration and prolonged retention, with the goal of enhancing the safety and tolerability profile by rapidly clearing from normal organs and tissues to minimize systemic radiation exposure. Our miniprotein radioconjugates are designed for use with either imaging isotopes to select patients expressing the target, or therapeutic isotopes to treat tumors. The radioconjugates are formed by a chelation reaction to bind the isotopes to DOTA, which is covalently linked to the tumor-targeting miniprotein. This approach will enable clinicians to first visualize and verify target tumor engagement using an imaging radioisotope, thereby identifying the patients who are most likely to benefit from our therapy. Our platform has enabled us to engineer potent, precision miniprotein-based radioconjugates that bind to the surface targets on tumor cells to localize radioisotope payloads. Miniproteins are polypeptides of less than one hundred amino acids that are amenable to biologic and medicinal chemistry optimization methods. We are prioritizing miniprotein binders of 40 to 70 amino acids in length, which are classified as biologics from a regulatory perspective providing a twelve-year exclusivity period for approved products. Miniproteins have differentiated and highly attractive properties as radioconjugates based on their antibody-like ability to potently and selectively bind to a highly diverse set of tumor targets, while having the pharmacologic profile of small peptides to enable high tumor penetration and rapid clearance from the body. We believe that miniproteins have many of the advantages of larger biologics like antibodies, as well as advantages of the smallest binders like peptides, without the limitations specific to either 7 class. In particular, based on our preclinical studies, we believe miniproteins have the following beneficial characteristics for use in radiopharmaceuticals: • Enhanced anticancer activity. Tumor killing is achieved through delivery of absorbed radiation dose, which is enhanced by high tumor penetration, high binding affinity for tumor targets, and prolonged retention of drug in the tumor. • Improved tumor penetration as compared to larger biologics. Due to their small diameters, miniproteins can achieve high tumor penetration. In contrast, antibodies are unable to rapidly penetrate tumors to the same extent due to their much larger size. • High affinity for tumor targets. Increased affinity is associated with higher tumor uptake. We have reproducibly generated sub-nanomolar affinity miniprotein binders to specific tumor targets. • Internalization into tumor cells and prolonged tumor retention . Our miniprotein radioconjugates are internalized into cancer cells, which we believe drives prolonged retention time in tumors. In a clinical imaging assessment, AKY-1189 was measured for two days following administration and robust tumor retention was observed through the duration of the assessment. In preclinical studies in animals with significantly faster plasma clearance than humans, we measured out to three days following administration and observed robust retention of AKY-1189 in the tumor for the duration of the study. • Enhanced clearance, selectivity and kidney exposure. • Rapid clearance from the body to minimize toxicities. The most common dose-limiting toxicity for targeted radiopharmaceuticals is hematologic and bone marrow toxicity. To lower the risk of radiation exposure to bone marrow, we have designed our product candidates to have a short plasma half-life in order to be rapidly cleared through the kidney. Rapid clearance of the radioisotope payload from the body minimizes the exposure to radiation of normal organs and tissues, such as the blood, bone marrow and skin. Unlike antibodies or other large biologic radioconjugates that take days to weeks to be eliminated from circulation, miniproteins are typically eliminated from circulation within hours, thereby minimizing systemic exposure and potentially increasing the therapeutic index of our miniproteins relative to other radiopharmaceutical constructs. • High selectivity. Miniproteins, like antibodies, can target specific isoforms or variants of closely related protein targets and differentiate among them, resulting in higher selectivity as compared to peptides. Our product candidates have demonstrated high selectivity for their tumor targets using a well-established cell-surface array assay. We believe this selectivity will reduce the risk of off-target binding and radioactive exposure to normal organs and tissues. • Reduced kidney exposure through molecular engineering. The kidney is not only the organ that clears miniproteins from the body but it also plays the physiologic role in reabsorbing renally-cleared peptides and proteins to reclaim nutrients. We have developed proprietary capabilities and expertise to engineer our product candidates to minimize their renal reabsorption. Based on data to date, we do not expect either of [ 225 Ac]Ac-AKY-1189 or [ 225 Ac]Ac-AKY-2519 to require renal protection strategies, such as pre-treatment with amino acids that are required for peptide-based radiopharmaceuticals targeting somatostatin-2 receptor, or SSTR2, such as Lutathera. • Broader number of addressable targets as compared to peptides. Miniproteins, like antibodies, bind to targets with high affinity, which enables highly selective and potent binding to targets through protein-protein intermolecular contacts. This allows miniproteins to bind to many, diverse protein targets, whether or not the protein target has a cleft or other structural feature commonly required for peptide binders. • Enables rapid advancement to development candidates. We utilize proprietary yeast surface display techniques that enable us to efficiently screen greater than five billion miniprotein variants and select the most promising candidates for advancement. Furthermore, unlike larger biologics, we couple biological in vitro evolution with medicinal chemistry. Medicinal chemistry utilizes solid phase peptide synthesis, which enables the rapid synthesis of miniproteins with site-specific modifications, including the incorporation of unnatural amino acids, to efficiently optimize our drug candidates to have beneficial characteristics likely to confer a strong clinical profile. • Enables rapid advancement into first-in-human evaluation. Unlike larger biologics, which require time-consuming and expensive recombinant manufacture by cells in culture, miniproteins allow for efficient chemical synthesis using solid phase peptide synthesis and rapid and cost-effective scale-up. • Lack of manufacturing constraints . For each clinically-administered dose, only microgram quantities of our miniprotein are anticipated to be required. The microdose quantities allow for small gram-scale batches of our miniprotein to be efficiently produced at contract manufacturers to enable development through first-in-human studies in contrast to other approved peptide drugs that require kilogram-scale batches. 8 We strengthen our miniprotein discovery workflow by incorporating artificial intelligence, or AI, technologies. We use various AI tools to help us select the best radiopharmaceutical biological targets, generate miniprotein libraries based on naturally evolved protein domains, design new miniprotein structures de novo using generative AI, and support our optimization efforts using machine learning models that are trained on our proprietary data. We can uniquely couple these state-of-the-art AI approaches with our wet-lab capabilities and our acquired expertise in discovery and optimization of miniprotein binders. Manufacturing and supply Manufacturing challenges and ensuring supply chain continuity and reliability have historically hindered the development and commercialization of radiopharmaceuticals. To overcome these challenges, we have established manufacturing and supply chain capabilities that are designed to be reliable and capital efficient with the ability to scale to meet global commercial demand for large cancer patient populations. Our end-to-end supply chain capabilities are orchestrated by our seasoned radiopharmaceutical development and manufacturing team that has experience advancing radiopharmaceutical programs from preclinical to commercialization. We have a state-of-the-art radiopharmaceutical development suite to apply our proprietary insights into process, formulation, and product development for preclinical, first-in-human, clinical trial, and commercial manufacturing and supply. In addition, we have multiple domestic and international isotope supply agreements spanning therapeutic and diagnostic uses, including agreements with NorthStar Medical Technologies, LLC, TerraPower Isotopes, LLC and Niowave, Inc., among others, with priority access to 225 Ac. We have partnered with leading contract manufacturing organizations to facilitate reliable and efficient supply, including co-located drug product manufacturing with 225 Ac and 64 Cu production to reduce costs, improve product turnaround time, and ease supply logistics, for our proprietary targeted miniprotein radiopharmaceutical precursors and products. Leveraging this network of partners, we are currently manufacturing drug product for our clinical trial. Additionally, we are building an internal cGMP radiopharmaceutical facility to enhance flexibility, increase control, and establish a hybrid internal and external clinical supply chain of our product candidates. We expect our manufacturing facility to be fully operational in the second half of 2026. As we grow our organization, we are continuing to evaluate options for internal commercial manufacturing to complement our network of commercial contract manufacturers. Our pipeline We are leveraging our proprietary miniprotein radioconjugate platform to discover and develop a deep pipeline of targeted radiopharmaceutical programs to address unmet needs in prevalent solid tumors. Our most advanced program, [ 225 Ac]Ac-AKY-1189, is targeting Nectin-4 expressing solid tumors, including locally advanced or metastatic UC, breast cancer, NSCLC, colorectal cancer and cervical cancer. Our second most advanced program, [ 225 Ac]Ac-AKY-2519, is targeting B7-H3 expressing solid tumors, such as prostate, lung and breast cancers. Beyond [ 225 Ac]Ac-AKY-1189 and [ 225 Ac]Ac-AKY-2519, we have a robust discovery pipeline of several unpartnered miniprotein radioconjugate programs in the discovery phase that focus on clinically-validated targets. Our learnings from the optimization of [ 225 Ac]Ac-AKY-1189 are being applied to benefit the development of [ 225 Ac]Ac-AKY-2519 and these subsequent programs. We retain exclusive, worldwide development and commercialization rights to all our current product candidates and discovery programs. We also have a discovery collaboration with Eli Lilly and Company, or Eli Lilly, to generate novel anticancer radiopharmaceuticals against targets beyond the scope of our unpartnered pipeline programs. 9 [ 225 Ac]Ac-AKY-1189 targeting Nectin-4 expressing tumors Our lead product candidate, [ 225 Ac]Ac-AKY-1189, was generated using our miniprotein radioconjugate platform and is designed to deliver 225 Ac, a highly potent alpha-emitting radioisotope, to Nectin-4 expressing tumors. Nectin-4 is a cell-surface protein found on a wide variety of tumors and has very limited expression in normal adult tissues. Nectin-4 is also the target of enfortumab vedotin, or Padcev, an approved ADC for the treatment of locally advanced and metastatic UC. Although Padcev has validated Nectin-4 as an oncology target, there has been limited clinical development activity to design other therapeutics targeting other Nectin-4 expressing tumors, which may be due to the need to develop a companion diagnostic for tissue testing when utilizing an ADC. In contrast, we intend to use imaging radioisotopes conjugated to AKY-1189 to readily select patients most likely to benefit from therapeutic treatment with [ 225 Ac]Ac-AKY-1189. We believe AKY-1189, when conjugated to a radioisotope, has the potential to treat UC as well as other Nectin-4 expressing tumors by selectively delivering cytotoxic radioisotopes such as 225 Ac to Nectin-4 expressing tumors to kill the tumor. AKY-1189’s short plasma half-life is designed to limit its radiation exposure to sensitive organs like bone marrow. We have also specifically designed AKY-1189 to minimize reabsorption by the kidneys to avoid potential toxicity concerns associated with renally-cleared radiopharmaceuticals. In our preclinical studies, [ 225 Ac]Ac-AKY-1189 has demonstrated antitumor activity and increased overall survival in animals inoculated with Nectin-4 expressing cancer cell xenografts. It also demonstrated a compelling biodistribution profile, with low absorbed doses observed outside of the tumor, which supports [ 225 Ac]Ac-AKY-1189’s potential to widen the therapeutic window. Furthermore, the Section 21 data included clinical imaging and dosimetry data from radioactive imaging radioisotope conjugates of AKY-1189, [ 68 Ga]Ga-AKY-1189 and [ 177 Lu]Lu-AKY-1189, which enabled assessment of tumor uptake and retention in 15 patients with solid tumors known to have high Nectin-4 expression, including UC, breast cancer, NSCLC, colorectal cancer and cervical cancer. In this assessment, AKY-1189 was observed to specifically localize and be retained in all tumor types examined, while being rapidly cleared from normal organs and tissues, including the kidney, with no adverse events observed. In this assessment, we also observed tumor uptake and retention at levels we expect to be sufficient to drive efficacious responses, based on similar measurements to those of leading marketed radiopharmaceuticals. We have commenced a multi-site Phase 1b trial in the United States for the treatment of locally advanced or metastatic UC and other Nectin-4 expressing tumors and anticipate preliminary results from the Part-1 dose escalation portion of this trial in the first quarter of 2027. An imaging radioisotope is being used to directly assess tumor binding by AKY-1189 and identify patients most likely to respond to [ 225 Ac]Ac-AKY-1189 with the aim of delivering early clinical therapeutic signals across multiple Nectin-4 expressing tumor types. Patients determined to be Nectin-4 positive will move to the [ 225 Ac]Ac-AKY-1189 dose-escalation portion of the trial. That phase of the study will investigate increasing doses of [ 225 Ac]Ac-AKY-1189. Following completion of each dose level, safety of the drug will be assessed by a safety review committee and, if deemed safe, enrollment of the next higher dose level will commence. In December 2025, we disclosed that we had completed the first dose level of the Part 1 dose escalation of the Phase 1b clinical trial and had commenced enrollment of the next dose level. Enrollment in the trial remains on track, and we expect to present data from the Part 1 dose escalation in the first quarter of 2027. Upon completion of the dose escalation portion, a dose expansion portion will be conducted in patients with locally advanced or metastatic UC and other Nectin-4 expressing tumors. [ 225 Ac]Ac-AKY-1189 was granted Fast Track Designation by the FDA in February 2026 for the treatment of locally advanced or metastatic UC in patients who had progressed on or after prior systemic therapies. [ 225 Ac]Ac-AKY-2519 targeting B7-H3 expressing tumors Our second product candidate, [ 225 Ac]Ac-AKY-2519, is designed to deliver 225 Ac to B7-H3 (CD276) expressing tumors, including prostate, lung and other solid tumors. B7-H3 is a cell-surface protein that is highly expressed in many types of solid tumors, while having limited expression in normal tissues. We estimate that approximately 90% of all metastatic castration-resistant prostate cancers, 80% of NSCLCs and 70% of small cell lung cancers, express B7-H3, while also being expressed on other solid tumors like breast cancers. High expression of B7-H3 has been associated with poor overall survival outcomes and a lack of responsiveness to anti-PD-1 therapeutics in several tumor types. B7-H3 has attracted substantial clinical development efforts across different modalities, including ADCs, with several late-stage ADCs demonstrating preliminary efficacy signals and acceptable safety profiles. Regarding the potential for B7-H3 as a target in prostate cancer, we believe B7-H3 to be differentiated from PSMA for imaging and treatment due to its high tumor expression and limited expression in normal organs and tissues, such as kidneys and salivary glands. In our preclinical studies, [ 225 Ac]Ac-AKY-2519 has demonstrated robust antitumor activity and increased overall survival in mice inoculated with B7-H3 expressing cancer cell xenografts. It also demonstrated a compelling biodistribution profile, with low absorbed doses observed outside of the tumor. [ 68 Ga]Ga-AKY-2519 and [ 177 Lu]Lu-AKY-2519 uptake in tumors and normal tissue biodistribution is currently being assessed in patients with various B7-H3 expressing solid tumors. To date, each of [ 68 Ga]Ga-AKY-2519 and [ 177 Lu]Lu-AKY-2519 has demonstrated robust tumor uptake with low uptake in normal tissues and a differentiated biodistribution profile, showcasing rapid clearance from normal organ and tissues, including kidneys. We expect the results of the imaging and dosimetry assessment in patients with various tumor types to be reported in mid-2026. In March 2026, our INDs for [ 225 Ac]Ac-AKY-2519 and for [ 64 10 Cu]Cu-AKY-2519 were cleared by the FDA to proceed to a Phase 1b clinical trial. We expect to initiate the multi-site Phase 1b clinical trial mid-2026. Eli Lilly collaboration In May 2024, we entered into a discovery collaboration with Eli Lilly to leverage our proprietary miniprotein radioconjugate platform to generate novel anticancer radiopharmaceuticals against targets beyond the scope of our unpartnered pipeline programs. We received a $60.0 million upfront cash payment in addition to an equity investment and are eligible to receive up to an additional $1.2 billion upon achievement of preclinical, clinical, regulatory, and commercial milestones, as well as tiered royalties. We are responsible for program discovery of a defined set of targets selected by Eli Lilly through initial human imaging studies and Eli Lilly is responsible for worldwide clinical development and commercialization from Phase 1 clinical trials onward. We retain worldwide rights to our proprietary pipeline programs, including our lead Nectin-4 targeting program. Our team We have assembled an experienced management team with deep expertise in drug development, approval, and commercialization, with members of our management being involved in the approval and commercialization of 14 currently marketed FDA-approved products. Our team is led by executives who have significant experience in company-building in the biopharmaceutical industry and a shared vision to build a leading radiopharmaceutical company. The experience of our President and Chief Executive Officer, Matthew Roden, PhD, in the biopharmaceutical industry includes leadership positions in corporate strategy and business development at Bristol Myers Squibb, and senior equity research coverage of the biotechnology sector at J.P. Morgan and UBS. He also serves as an Entrepreneur Partner at MPM BioImpact and on the Boards of Directors of other biotechnology companies. Our Chief Financial Officer, Kyle D. Kuvalanka, brings over 20 years of experience as a senior leader in the biopharmaceutical industry, having served in executive leadership roles at ROME Therapeutics, Syros Pharmaceuticals, Blueprint Medicines and Goldfinch Bio. Paul L. Feldman, PhD, our Chief Scientific Officer, was Co-founder and Chief Executive Officer of Phoundry Pharmaceuticals and, upon its acquisition by Intarcia Therapeutics, served as Head of Discovery and Translational Medicine at Intarcia. In his previous roles at GlaxoSmithKline, he was directly involved in the discovery of five approved drugs. Shulamit Ron-Bigger, PhD, our Chief Operating Officer, previously served as Head of Strategy and Operations for the Research and Early Development organization at Bristol Myers Squibb. Akos Czibere, MD, PhD, our Chief Medical Officer, has extensive experience in clinical development, most recently serving as Therapeutic Area Development Head of Hematology-Oncology at Pfizer. Dr. Czibere has been directly involved in the approval of six oncology drugs, including Elrexfio and Talzenna. Tyler Benedum, PhD, our Chief Technical Officer, previously served as Vice President of Chemistry, Manufacturing, and Controls Development at Avid Radiopharmaceuticals, a wholly-owned subsidiary of Eli Lilly, where he oversaw global commercial and clinical trial radiopharmaceutical manufacturing and played a key role in developing and advancing Amyvid and Tauvid through marketing authorization approval and commercialization. Our company was co-founded by Todd Foley, a Managing Director at MPM BioImpact, who is currently Chair of our Board of Directors; Patrick Baeuerle, PhD, an MPM BioImpact Advisor, and currently a member of our Scientific Advisory Board; and Brian Goodman, PhD, a Partner at Vida Ventures. Expanding the potential of radiopharmaceuticals We believe that the field of radiopharmaceuticals is still in its infancy and is poised to become a fundamental pillar of cancer care and deliver transformative survival and quality of life outcomes for patients. External beam radiation therapy, or EBRT, has proven to be an effective option for cancer treatment but has limitations including lack of sufficient precision to avoid collateral damage to normal organs and tissues. Radiopharmaceuticals have the ability to deliver high levels of radiation directly and precisely to diseased tissue by combining the proven tumor-killing ability of radiation therapy with the high degree of molecular precision provided by their targeting components, offering cancer patients better outcomes than other anticancer modalities. Several radiopharmaceutical drugs have been developed and commercialized in an expanding field, demonstrating the significant market potential of radiopharmaceuticals. Commercial adoption of Pluvicto and Lutathera, along with expanding operational and commercial infrastructure, positions radiopharmaceuticals as the next emerging modality. To date, the development of radiopharmaceutical candidates has been primarily focused on two biological targets: PSMA, the target of Pluvicto; and SSTR2, the target of Lutathera. Our company was founded with the aim of maximizing the impact of radiopharmaceuticals by bringing excellence to all aspects of radiopharmaceutical drug development, by discovering therapeutic candidates that broaden the set of targets and tumors that are addressed by radiopharmaceuticals. As a result, none of our programs target PSMA or SSTR2. We instead focus on leveraging our miniprotein radioconjugate platform to a broader set of addressable targets such as Nectin-4 and B7-H3, which are expressed in tumor types such as lung, breast, bladder, prostate and gastrointestinal tumors, and collectively account for an estimated 193,000 and 215,000 incident cases per year, respectively. Radioisotopes used in radiopharmaceuticals fall into two classes: alpha-emitting and beta-emitting radioisotopes. Alpha particles are much larger and heavier than beta particles, with higher energy and shorter travel distances. Although both alpha-emitting and beta-emitting radioisotopes cause damage to the DNA of tumor cells resulting in tumor cell death, there are distinct differences. Beta-emitting radioisotopes create single-strand DNA breaks and can travel to more distant cells not in direct contact with the delivery point of the radiopharmaceutical. In contrast, alpha-emitting radioisotopes create catastrophic double-stranded 11 DNA breaks and are 1,000 times more potent in cell killing than beta-emitters but can only travel two to three cell lengths. Radiopharmaceuticals using alpha-emitting radioisotopes also offer advantages with administration as they result in less radiation exposure to the clinic staff during administration, as well as convenience to patients with no post-treatment restrictions on having contact with other people. In third-party studies, alpha-emitting radioconjugates have also demonstrated increased anticancer activity in patients with tumors that did not respond to beta-emitting radioconjugates. As seen in the graphic below, a patient with widespread metastatic disease was observed to have progressive disease following treatment with two cycles of 177 Lu-PSMA-617. Subsequent treatment with 225 Ac-PSMA-617 resulted in profound regression of disease. Objective response rates of over 30% have been observed in academic trials of 225 Ac-PSMA-617, and a recent company-sponsored trial of 225 Ac-containing PSMA-617 radioligand showed a 43% response rate in patients previously treated with 177 Lu-containing PSMA-617 radioligand therapies. These results illustrate the powerful efficacy potential for 225 Ac-containing targeted radioconjugates. Anticancer activity of alpha-emitting radioconjugates in patients with tumors that did not respond to beta-emitting radioconjugates We believe alpha radioconjugates represent a significant opportunity for improved clinical outcomes for patients with cancer. Due to the inherent advantages and breakthrough efficacy potential, we are initially focused on alpha-emitting radioisotopes. However, our miniprotein radioconjugates have the ability to deliver both alpha-emitting and beta-emitting radioisotopes, which we believe expands the potential impact and tumor treatment options available for our radiopharmaceuticals. Our proprietary miniprotein radioconjugate platform We were founded to improve outcomes for cancer patients by pioneering a new class of targeted radiopharmaceuticals to unlock the benefit of the modality for prevalent tumor types that have historically been beyond the reach of radiopharmaceuticals. Our ability to leverage the killing power of a radioconjugate provides significant opportunity for discovering targeted radiopharmaceuticals with the potential to transform the cancer treatment paradigm for patients with a broad set of tumor types. Our aim is to discover targeting molecules that can bind with high affinity and prolonged duration on cancer cells to maximize efficacy, while having high selectivity and short residence time in the rest of the body to avoid toxicity to normal organs and tissues. Our founders created our company with a focus on a category of polypeptides, referred to as miniproteins. Miniproteins consist of manifold scaffolds of less than one hundred amino acids in length that fold into a stable tertiary structure, making them larger than small peptides but smaller than large biologics. Similar to larger biologics, such as antibodies, miniproteins possess the ability to recognize and bind with high selectivity to a highly diverse set of tumor targets, but lack some of the known radiopharmaceutical property limitations of antibodies, including long circulating half-life and poor tumor uptake. Miniproteins also share some of the pharmacological profile advantages of small peptides such as high tumor penetration and short plasma half-life. However, miniproteins are able to bind to, and exhibit high selectivity for, tumor targets that are less tractable with smaller peptides. We believe miniproteins possess pharmacological properties that make them ideal targeting molecules for radiopharmaceutical product development, since they retain the advantages of large biologics and smaller peptides without the limitations specific to either class. We are focused on the discovery of novel miniproteins that are 40 to 70 amino acids in length, which categorizes them as biologics from a regulatory perspective, providing a twelve-year exclusivity period for approved products. Our miniprotein radioconjugates offer both the potential for both potent antitumor activity and an enhanced safety and tolerability profile. The small size of miniproteins allows them to rapidly penetrate tumors. Furthermore, our miniprotein radioconjugates are able to internalize into cancer cells, which we believe drives prolonged retention. We have reproducibly 12 generated high affinity miniprotein binders to specific tumor targets. Tumor killing is achieved through delivery of absorbed radiation dose, which is enhanced by high tumor penetration, high binding affinity for tumor targets, and prolonged retention of drug in the tumor. Two of the major concerns for toxicity with radiopharmaceuticals are renal damage due to radiation exposure in the kidney and hematological toxicity due to bone marrow exposure. The short plasma half-lives of miniproteins results in rapid clearance through the kidneys, limiting the overall radiation exposure of normal organs and tissues, such as the blood, bone marrow and skin, while the high target selectivity of our miniproteins further reduces off-target binding and exposure risk. We have built on this beneficial profile and engineered our product candidates to minimize their renal reabsorption using primary sequence modifications. Our lead optimization efforts have resulted in decreases in renal retention and increases in tumor uptake, which attributes are predicted to widen the therapeutic index of our product candidates relative to other radiopharmaceutical constructs. Our miniprotein platform is designed to broaden the number of tumor targets addressable by radiopharmaceuticals. Our miniproteins bind to targets with high affinity, which enables highly selective and potent binding to targets through protein-protein intermolecular contacts and allows them to potentially bind to many protein targets, whether or not it has a cleft or other structural feature commonly required for peptide binders. Our platform enables rapid advancement to product candidate and first-in-human evaluation. Miniproteins can be synthesized using solid phase peptide synthesis. This allows the evaluation of a large number of variants and enables the establishment of rich structure-activity relationships and site-specific modifications, including the incorporation of unnatural amino acids, to optimize for the desired drug-like properties. Our proprietary miniprotein radioconjugate platform uniquely combines the following non-exhaustive list of technologies we use during our discovery process: • novel, proprietary libraries of greater than 100 miniprotein scaffolds that enable yeast surface display selections of approximately five billion variants; • machine-learning based design and optimization of miniprotein variants; • unique biological assays to rapidly assess our miniprotein radioconjugate candidates; and • medicinal chemistry enabling site-specific incorporation of proprietary unnatural amino acids into our miniprotein radioconjugates to optimize pharmacological properties. We routinely apply our platform to rapidly generate and optimize miniprotein binders to tumor cell targets, not only selecting for product candidates that bind to their targets with high selectivity and affinity, but also optimizing for other properties that we believe will increase their potential as high-value therapeutics. As illustrated below, this iterative process to optimize miniproteins utilizes computational design with biological evolution and medicinal chemistry. Iterative process optimizing miniprotein discovery combines computational design, biological evolution and medicinal chemistry. Learnings from our Nectin-4 program and discovery programs have enabled additional technological advancements to be incorporated into subsequent programs, including our B7H3 program, to enhance our miniprotein radioconjugate platform and efficiently advance novel radiopharmaceutical programs. Enhancing our discovery efforts by utilizing AI AI, and its sub-categories of machine learning, deep learning, generative AI, and expert systems, are making a significant impact in the pharmaceutical industry and spawning many new companies and technologies. We have been utilizing AI to advance our miniprotein discovery and development over the past several years. Our reliance on AI has increased with advancement of AI tools, especially with accumulation of experimental data that informs AI models. Within discovery, we use AI tools to help us select radiopharmaceutical biological targets, generate miniprotein libraries based on naturally evolved protein domains, and design new 13 miniprotein structures de novo using generative AI. In addition, we apply machine learning to critical experimental datasets and use structure-based modeling to support optimization of our miniprotein binders. Recent advances in de novo design software have been used to design small-molecule, peptide, macrocycle, and antibody binders to proteins. More recently, this software has been adapted and modified by us and others to design miniprotein binders to biological targets. We can uniquely couple these state-of-the-art AI approaches with our wet-lab capabilities and our acquired expertise in discovery and optimization of miniprotein binders. We utilize AI tools throughout the entire process of advancing our radiopharmaceutical pipeline. In particular, we apply AI technology and yeast surface display to discover miniprotein binders to targets of interest in two ways: (1) to re-engineer naturally evolved protein-domain folds into libraries with hundreds of millions of variants each, from which target-binding miniproteins are captured by yeast surface display, and (2) to design novel miniproteins specifically for binding to biological targets of interest, and to use yeast surface display to identify the most successful designs. In addition to our internal work using and advancing AI tools, we continue to assess potential third-party partners who are using AI tools, in order to further advance our specific discovery capabilities. [ 225 Ac]Ac-AKY-1189: Our lead product candidate targeting Nectin-4 expressing tumors Our lead product candidate, [ 225 Ac]Ac-AKY-1189, was discovered using our miniprotein platform and is designed to deliver 225 Ac, a highly potent alpha-emitting radioisotope, to Nectin-4 expressing tumors. The therapeutic potential of [ 225 Ac]Ac-AKY-1189 is supported by our preclinical studies and an investigator-initiated clinical imaging and dosimetry assessment demonstrating the ability of AKY-1189 radioconjugates to specifically localize to Nectin-4-expressing tumors and rapidly clear from normal organs and tissues. In April 2025, the FDA cleared our IND for [ 225 Ac]Ac-AKY-1189 for the treatment of locally advanced or metastatic UC and other Nectin-4 expressing tumors. We have commenced a multi-site Phase 1b clinical trial in the United States and anticipate preliminary results from the Part-1 dose escalation portion of this trial in the first quarter of 2027. [ 225 Ac]Ac-AKY-1189 was granted Fast Track Designation by the FDA in February 2026 for the treatment of locally advanced or metastatic UC in patients who had progressed on or after prior systemic therapies. Nectin-4: a clinically validated oncology target Nectin-4 is the target of Padcev which is approved worldwide for the treatment of locally advanced or metastatic UC. Nectin-4 is a surface protein that is expressed in a wide variety of solid tumor types and has very limited expression in normal adult tissues. Robust expression of Nectin-4 has been reported in various solid tumor indications, including UC, breast, NSCLC, colorectal, pancreatic, ovarian, cervical, head and neck, gastric, and esophageal cancers, with Nectin-4 expression levels of approximately 50%-95% observed in multiple tumor types. Up to an estimated 193,000 cancer patients are diagnosed annually in the United States with solid tumors that may express Nectin-4. The expression of Nectin-4 is associated with poor patient prognosis and unfavorable tumor progression. We believe that elevated Nectin-4 expression in these solid tumors supports our ongoing evaluation of [ 225 Ac]Ac-AKY-1189 in UC and beyond. Elevated Nectin-4 mRNA expression expressed in multiple tumor types 14 Background on UC and other Nectin-4 expressing solid tumors UC is a cancer that begins in the cells that line the urethra, bladder, ureters, renal pelvis and other organs. Over 90% of bladder cancers in the United States are UCs. The National Cancer Institute estimated that there would be greater than 83,000 new cases of bladder cancer and approximately 16,800 bladder cancer related deaths in the United States in 2024. Bladder cancer represents 4% of all cancers in the United States and is the fourth most common cancer in men, though less common in women. In 2024, the total number of patients with locally advanced or metastatic UC in the United States was estimated to be approximately 18,000. Annually, an estimated 4,200 patients are diagnosed with metastatic UC. Until recently, the most common treatment for patients diagnosed with locally advanced or metastatic UC was chemotherapy with platinum-based drugs, such as carboplatin or cisplatin in combination with gemcitabine. Patients with metastatic disease that progressed during or after platinum-based chemotherapy were increasingly being treated with checkpoint immunotherapy. A number of PD-1 and PD-L1 checkpoint inhibitors have been approved by the FDA for use in refractory bladder cancer with objective response rates observed in clinical trials between 15% to 21%. Due to the ubiquitous and robust expression of Nectin-4 in UC, no companion diagnostic or tissue testing for Nectin-4 is required. To date, there is only one approved Nectin-4 targeted therapy for UC, the ADC enfortumab vedotin, marketed as Padcev by Pfizer and Astellas. Padcev in combination with pembrolizumab is the standard of care for first-line treatment of patients with locally advanced or metastatic UC with no clear standard of care for subsequent lines of therapy. In locally advanced or metastatic UC patients previously treated with a PD-1 or PD-L1 inhibitor and/or platinum-based chemotherapy, treatment with Padcev monotherapy led to a 40.6% overall response rate and improved overall survival to 12.9 months compared to 9.0 months for patients treated with chemotherapy. In treatment-naïve patients with locally advanced or metastatic disease, Padcev in combination with pembrolizumab led to a 67.7% overall response rate and an overall survival of 31.5 months compared to 16.1 months for patients treated with chemotherapy. These data from Padcev in combination with pembrolizumab led to its recommendation as a first-line treatment for patients with locally advanced or metastatic bladder cancer. Sales of Padcev in 2024 were approximately $1.9 billion with estimated peak sales of up to $7.0 billion. Although Padcev received initial regulatory approval from the FDA in 2019 for the treatment of locally advanced or metastatic UC, it has not been approved for the treatment of other Nectin-4-expressing tumors and there has been limited clinical development activity to design therapeutics targeting other Nectin-4 expressing tumors, which may be due to the need to develop a companion diagnostic for tissue testing when utilizing an ADC. In clinical trials leading to the initial approval of Padcev, Nectin-4 expression was observed in all 120 UC patients with available tumor biopsies, and the FDA agreed that the use of an in vitro diagnostic for Nectin-4 expression was not essential to the safe and effective use of Padcev. Other cancers, including breast, NSCLC, colorectal and cervical have been shown to express Nectin-4, though overexpression may not be as ubiquitous as in UC. Breast cancer is the second most common type of cancer in women in the United States with more than an estimated 360,000 patients diagnosed in 2024. Lung cancer is the third most common cancer in the United States with 235,000 patients diagnosed annually and more people in the United States dying from lung cancer than any other type of cancer. NSCLC is the most common type of lung cancer, accounting for about 80% to 85% of all lung cancer cases. Colorectal cancer develops in the colon or rectum with 150,000 new cases in the United States estimated in 2024. Cervical cancer starts in the cells lining the cervix, the lower part of the uterus, and it is estimated that approximately 13,800 new cases of invasive cervical cancer were diagnosed in the United States in 2024. We believe there is a significant opportunity to develop novel therapies with improved therapeutic profiles in these large patient populations with significant unmet medical needs. Our solution: [ 225 Ac]Ac-AKY-1189 Our lead product candidate, [ 225 Ac]Ac-AKY-1189, contains a miniprotein, AKY-1189, that specifically binds to Nectin-4, which is conjugated via chelation to 225 Ac. AKY-1189 is a 45-amino-acid miniprotein covalently attached to an established radioisotope chelator, DOTA, through a short, chemically stable linker. In our preclinical mouse models, AKY-1189 was observed to specifically localize to Nectin-4 expressing tumors while minimizing exposure to the kidneys and other normal organs and tissues. Clinical imaging and dosimetry assessments using [ 68 Ga]Ga-AKY-1189 and [ 177 Lu]Lu-AKY-1189 in patients demonstrated high tumor uptake of AKY-1189 in UC and four other tumor types known to express Nectin-4, while being rapidly cleared from the body and avoiding normal organs and tissues. Discovery and development of AKY-1189 utilizing our miniprotein radioconjugate platform We have leveraged our proprietary miniprotein radioconjugate platform to discover and develop AKY-1189 following an evaluation of millions of potential candidates through a combination of computational modeling, directed evolution, functional screening, in vivo profiling and medicinal chemistry. Our approach enabled us to optimize the physicochemical, potency, and pharmacological properties of miniprotein binders that led to the discovery of AKY-1189. AKY-1189 is engineered to be thermally stable to at least 75°C to enable the manufacture of [ 225 Ac]Ac-AKY-1189. The conjugated radiopharmaceutical is designed to maintain radiochemical stability for at least four days to support central manufacturing and enable flexible distribution and clinical administration. 15 The binding affinity, referred to as K D , of AKY-1189 to Nectin-4 was determined to be 0.22 nanomolar, or nM, by surface plasmon resonance. The K i , or inhibitory constant, which also measures binding affinity, of this miniprotein to Nectin-4 expressing tumor cells was determined to be 0.82 nM, and within the range of 0.1 nM to 1 nM targeted by therapeutic antibodies designed to deliver cytotoxins to tumors, such as ADCs. No off-target binding of AKY-1189 was detected when tested at a concentration of 450 times higher than its K D for Nectin-4. This selectivity testing was conducted for more than 6,200 surface expressed or secreted proteins, including Nectin-1, -2, and -3. Furthermore, no binding was observed in a tumor cell line in which the gene for Nectin-4 had been removed by CRISPR knockout. We believe the binding affinity and selectivity of AKY-1189 supports a favorable risk-benefit profile. In addition to high Nectin-4 binding affinity, we designed AKY-1189 to be minimally retained in the kidney. Our optimization process is exemplified by examining the progression of the properties from our earlier Nectin-4 targeted miniproteins, AKY-807 and AKY-1162, to AKY-1189. In vitro binding assays demonstrated that AKY-807 was a potent and selective binder to Nectin-4 expressing tumor cells but in vivo imaging studies with an imaging radioisotope, [ 111 In]In-AKY-807, demonstrated that the AKY-807 also localized to the kidneys. However, while some localization in the kidneys was expected given renally-cleared molecules are subject to reabsorption in the kidney, we observed that high levels remained in the kidneys for 22 hours after dosing. Through a series of sequence modifications to the miniprotein, we generated a series of molecules, including AKY-1162 and AKY-1189, that improved the Nectin-4 binding affinity and tumor binding, while simultaneously reducing kidney retention. As seen in the images below, there was considerable improvement in the lack of kidney retention, coupled with improvement in tumor uptake from AKY-807 to AKY-1162 to AKY-1189. AKY-1189’s rapid tumor uptake and kidney washout 22 hours after administration compared with previous miniproteins Brightly colored areas depict presence of imaging radioisotope in mice implanted with xenograft tumors on right forelimb Figure left shows low kidney uptake and more rapid washout of AKY-1189 over 22 hours compared to other miniproteins. Figure right depicts more rapid and retained tumor uptake of AKY-1189 over 22 hours compared to other miniproteins. In vivo preclinical studies Tumor and normal tissue uptake To assess the potential of AKY-1189 in tumor xenograft models we used two versions of the HT-1376 human UC cell line, which is epithelial-like cell isolated from the urinary bladder of a patient with cancer. The expression levels were determined by 16 histochemical staining and scored using the Histochemical Scoring Assessment, or H-score, which has a range of 0-300, with higher scores representing higher expression. In one cell line, noted as low expression in the image below, Nectin-4 expression was limited to the endogenous levels of the cell line, with an H score of 175. In the other cell line, noted as representative expression in the image below, we used genetic engineering to increase the level of Nectin-4 expression to more closely match that observed in representative metastatic UC patient biopsies, with an H-score of 291. Between 55% to 90% of metastatic UC patients are initially diagnosed with a H-score similar to the representative expression cell line. Nectin-4 expression in the modified HT-1376 cell line matched that observed in a representative biopsy from a metastatic UC patient that has high levels of Nectin-4 expression We assessed the ability of AKY-1189 to localize to tumors in a mouse xenograft model using the representative Nectin-4 expressing HT-1376 cell line. Dosing with the imaging radioisotope [ 111 In]In-AKY-1189 allowed quantitative measurement of [ 111 In]In-AKY-1189 biodistribution using single-photon emission computed tomography, or SPECT, imaging. Within minutes of dosing, the highest levels of [ 111 In]In-AKY-1189 were found in the tumor. These levels in the tumor were maintained for approximately two hours, after which the levels slowly declined over the 24-hour observation period, with retention observed for up to three days after dosing. In contrast, the levels of [ 111 In]In-AKY-1189 observed in the kidneys rose within minutes after dosing and then rapidly declined as [ 111 In]In-AKY-1189 was eliminated from the body. This desired preclinical biodistribution profile, high tumor uptake and reduced exposure to organs and normal tissues, supported the advancement of [ 225 Ac]Ac-AKY-1189. We believe this biodistribution profile enables a wide therapeutic window for [ 225 Ac]Ac-AKY-1189 in treating patients with Nectin-4 expressing tumors. AKY-1189 was localized and retained in tumors, while being rapidly washed out from the kidneys Brightly colored areas depict presence of imaging radioisotope four hours after dosing (left) and 24 hours after dosing (right), in mice implanted with xenograft tumors on right forelimb 17 Figure left shows low kidney uptake and rapid washout of AKY-1189 over 24 hours. Figure right depicts high, rapid and retained tumor uptake of AKY-1189 over 24 hours. Based on our modeling of the pharmacokinetics of AKY-1189 and scaling to projected human doses, we estimate that a dose of 7.4 MBq of [ 225 Ac]Ac-AKY-1189, a standard dose of 225 Ac-based radiopharmaceuticals that has demonstrated anticancer effects, will result in a low systemic and kidney exposure to radiation. The ability to deliver a radiopharmaceutical at a dose that is both safe and efficacious is critical and these preclinical predictions lie well within what we believe is a viable range for eventual clinical development and, if approved, commercialization. We believe that the therapeutic window of [ 225 Ac]Ac-AKY-1189 can improve tolerability and patient quality of life and provide the opportunity to potentially explore higher doses that could improve efficacy. The profile of [ 225 Ac]Ac-AKY-1189 provides the potential for flexibility in both the schedule and administered dose before approaching the EBRT benchmark limit of 23 RBE5Gy for kidneys. This is a level at which EBRT has been associated with a risk of chronic kidney disease in five percent of patients five years after dosing. Dosimetry scaling suggests that the radiation exposure to the kidney in humans will be well within the range generally considered to be acceptable in the field and below thresholds associated with kidney toxicity Antitumor activity of [ 225 Ac]Ac-AKY-1189 As shown below, [ 225 Ac]Ac-AKY-1189 also had increased antitumor activity in both high and low Nectin-4 expressing tumors in xenograft models. In our preclinical study, we observed that mice bearing HT-1376 tumors expressing low or representative levels of Nectin-4 were administered with either a single intravenous dose of 1 µCi, or microcuries, of [ 225 Ac]Ac-AKY-1189 or vehicle (n=8 mice per group). Treatment with [ 225 Ac]Ac-AKY-1189 resulted in a mean tumor regression of 53% in the representative Nectin-4 expressing tumors by day 25 (n=8 remaining animals) and an overall survival rate of 75% at the end of an eight-week observation period where median survival was not reached during the observation period. Treatment with vehicle in the representative Nectin-4 expressing tumors had no surviving animals at the end of the observation period and had a median overall survival of 28.5 days (n=5 remaining animals at day 25). In low Nectin-4 expressing tumors, [ 225 Ac]Ac-AKY-1189 treatment led to an average tumor growth inhibition of 62% at day 25 (n=8 remaining animals at day 25) and led to a median survival of 49 days. In low Nectin-4 expressing tumors, treatment with vehicle led to a median survival of 26.5 days (n=6 remaining animals at day 25). Body weight was monitored as a surrogate of overall animal health. Animal weights remained constant throughout the treatment period, indicating that [ 225 Ac]Ac-AKY-1189 treatment was well tolerated. 18 [ 225 Ac]Ac-AKY-1189 had increased antitumor activity in both high and low Nectin-4 expressing tumors in xenograft models Furthermore, treatment of mice harboring HT-1376 tumors with a single dose of [ 225 Ac]Ac-AKY-1189 resulted in improved tumor growth inhibition compared to multiple doses of Padcev, assessed in the same study. The mice expressing low levels of Nectin-4 were treated with a single intravenous dose of 2 µCi of [ 225 Ac]Ac-AKY-1189 on day zero. As depicted below, this resulted in a mean tumor growth inhibition of 75% at day 38 compared to 53% inhibition after three administrations of Padcev on day zero, 7 and 14 (depicted in figure A below). Animal weights remained constant during the treatment period, indicating that both regimens were well-tolerated (depicted in figure B below). To compare the antitumor activity and tolerability of Padcev, we calculated the dose to be used in mice based off the approved clinical dose and regimen. The dosing regimen used for Padcev of 3mg/kg once a week for three weeks in mice, demonstrated plasma exposures with an area under the curve, or AUC, of 88 µg*day/mL (depicted in figure C below), similar to those observed in patients treated with the clinical regimen of 1.25mg/m 2 (AUC = 111+38 µg*day/mL). AUC is a measure of drug exposure over time. When comparing this clinically relevant dose of Padcev to [ 225 Ac]Ac-AKY-1189, we observed a favorable response for [ 225 Ac]Ac-AKY-1189 in Padcev responsive tumors. A single administration of [ 225 Ac]Ac-AKY-1189 resulted in greater inhibition of tumor growth than Padcev in low Nectin-4 expressing tumors in xenograft models C max denotes maximum drug concentration; T 1/2 denotes time required to decrease drug concentration by half 19 Named patient use pursuant to Section 21 of South Africa’s Medicines and Related Substances Act Mike Sathekge, MD, Head of Nuclear Medicine Department, University of Pretoria and Steve Biko, Academic Hospital, and President and Chief Executive Officer, Nuclear Medicine Research Infrastructure, or NuMeRI, administered radioconjugated AKY-1189 provided by us to a limited number of their patients in South Africa pursuant to Section 21 of the MRSA, which allows healthcare providers to administer unregistered medicines to patients, as authorized by SAPHRA. AKY-1189 conjugated to an imaging radioisotope, [ 68 Ga]Ga-AKY-1189, was dosed in 20 patients with UC, breast cancer, NSCLC, colorectal cancer and cervical cancer. Of these 20 patients, all 20 were available for safety and normal tissue distribution assessment, and 15 were evaluable for tumor uptake. A subset of nine patients underwent kidney dosimetry with [ 177 Lu]Lu-AKY-1189 and eight patients were evaluable for quantitative assessment of the absorbed dose of radiation to the kidney and bone marrow. One patient also received AKY-807 conjugated to the same imaging isotopes allowing for intra-patient comparison of tumor uptake and absorbed dose to the kidney. In line with the preclinical predictions, AKY-1189 showed superior tumor uptake with less radiation exposure to the kidneys compared to AKY-807, with no adverse events observed. The figure below depicts normal tissue distribution of [ 68 Ga]Ga-AKY-1189, and robust tumor uptake, including in brain metastasis. Dark areas in the image below depict uptake of [ 68 Ga]Ga-AKY-1189. Representative PET/CT image of a patient dosed with [ 68 Ga]Ga-AKY-1189 after 1 hour Tumor uptake was evaluated with [ 68 Ga]Ga-AKY-1189 in 15 patients via PET/CT one hour post-injection. Standard uptake values, or SUVs, were calculated using standard methodology also utilized in standard diagnostic PET/CT images. As depicted in the chart below, SUVs were consistently at or above the levels expected to be required for efficacy and in line with SUVs reported for approved radiopharmaceuticals. This was observed across all tumor types assessed including UC, breast cancer, NSCLC, colorectal cancer and cervical cancer, as depicted in the image below on the left. For context, in an editorial published in 2023, Michael Hofman depicted the observed SUV max for various approved radiopharmaceuticals, including Pluvicto, Lutathera and 20 purported next alpha generation therapies. His study set forth the observed SUV max for PSMA and SSTR in the range from 10-100, as depicted in the image below on the right. [ 68 Ga]Ga-AKY-1189 tumor uptake across assessed tumor types suggests actionable therapeutic range Uptake of approved radiopharmaceuticals targeting PSMA and SSTR2 SUV in regions of interest including the primary and metastatic tumor deposits at 1 hour Hierarchy of SUVs: from left to right, iodine-131, PSMA, somatostatin receptor (DOTATATE), fibroblast activation protein inhibitor, and purported next-generation theranostics (referenced as “game changing” in the article). Increasing tumor uptake with [ 177 Lu]Lu-AKY-1189 with no accumulation observed in normal tissues observed at 48 hours 1 ~5.55 GBq (150mCi) administered activity The figures above depict normal tissue deposition and tumor uptake of [ 177 Lu]Lu-AKY-1189 during a 48-hour period. Dark areas in image depict tissue and tumor uptake of [ 177 Lu]Lu-AKY-1189. At 24 hours post administration, [ 177 Lu]Lu-AKY-1189 exposure increased in the tumors without accumulation of exposure to normal tissues. The [ 177 Lu]Lu-AKY-1189 data suggests the predicted absorbed dose to the kidney (median absorbed dose of 0.30 gray/gigabecquerel, or Gy/GBq) and bone marrow (median absorbed dose: 0.01 Gy/GBq) allows for six or more therapeutic doses to be safely administered. These data are consistent with other approved radiopharmaceuticals, including Pluvicto, where the kidneys and bone marrow are not considered dose-limiting organs, when conjugated to either 177 Lu or 225 Ac. We plan to evaluate these findings in future clinical trials. Our clinical development strategy In April 2025, the FDA cleared our IND for [ 225 Ac]Ac-AKY-1189 for the treatment of locally advanced or metastatic UC and other Nectin-4 expressing tumors. We have commenced a multi-site Phase 1b clinical trial in the United States and anticipate preliminary results from the Part-1 dose escalation portion of this trial in the first quarter of 2027. The Phase 1b trial in the United States will enroll approximately 150 patients and follow a dose escalation strategy utilizing the Bayesian Optimal Interval, or BOIN, 21 design, which is a method used for early phase dose-finding based on model-assisted design elements and is used to determine a suitable dose for consideration in later-stage oncology trials. The Phase 1b trial will only enroll patients with locally advanced or metastatic UC in the dose escalation portion. Imaging and dosimetry in the United States trial will be done with [ 64 Cu]Cu-AKY-1189 allowing for multiple timepoint assessments through PET/CT. No imaging selection criteria are employed through dose escalation. Patients will receive up to six cycles of [ 225 Ac]Ac-AKY-1189 at increasing dose levels. Following completion of dose escalation, dose expansions will be conducted in locally advanced or metastatic UC (n=30), triple-negative breast cancer (n=30) and a basket cohort of other tumors known to have high Nectin-4 expression, including NSCLC, colorectal cancer and cervical cancer (n=40). The primary endpoint of the trial will be to assess safety and tolerability of [ 225 Ac]Ac-AKY-1189. Secondary endpoints include objective response rate (as measured by RECIST v1.1, a standard way to measure the response of a tumor to treatment), duration of response, progression-free survival, overall survival, changes in quality of life, and to characterize pharmacokinetic and pharmacodynamic profiles. In December 2025, we disclosed that we had completed the first dose level of the Part 1 dose escalation of the Phase 1b clinical trial and had commenced enrollment of the next dose level. Enrollment in the trial remains on track, and we expect to present data from the Part 1 dose escalation in the first quarter of 2027. Upon completion of the dose escalation portion, a dose expansion portion will be conducted in patients with locally advanced or metastatic UC and other Nectin-4 expressing tumors. Based on the results of our trial, we plan to seek alignment with the FDA to conduct a pivotal Phase 2 trial for accelerated approval of [ 225 Ac]Ac-AKY-1189 for locally advanced or metastatic UC and other Nectin-4 expressing tumors. [ 225 Ac]Ac-AKY-1189 was granted Fast Track Designation by the FDA in February 2026 for the treatment of locally advanced or metastatic UC in patients who had progressed on or after prior systemic therapies. [ 225 Ac]Ac-AKY-2519 targeting B7-H3 expressing tumors Our second product candidate, [ 225 Ac]Ac-AKY-2519, is designed to deliver 225 Ac to B7-H3 (CD276) expressing tumors, including prostate, lung and other solid tumors. B7-H3 is a cell-surface protein that is highly expressed in many types of solid tumors, while having limited expression in normal tissues. In the United States, an estimated 146,000 patients are diagnosed with metastatic NSCLC, small cell lung cancer or prostate cancer annually. We estimate that approximately 90% of all metastatic castration-resistant prostate cancers, 80% of NSCLCs and 70% of small cell lung cancers, express B7-H3, while also being expressed on other solid tumors like breast cancers. High expression of B7-H3 has been correlated with poor overall survival and a lack of responsiveness to anti-PD-1 therapeutics in several tumor types. B7-H3 has attracted substantial clinical development efforts across different modalities, including antibody-drug conjugates, with several late-stage antibody-drug conjugates demonstrating preliminary efficacy signals and acceptable safety profiles. Regarding the potential for B7-H3 as a target in prostate cancer, we believe B7-H3 may be superior to PSMA for imaging and treatment of patients with prostate cancer due to higher sensitivity and tumor specificity with a clean normal tissue expression profile. We discovered AKY-2519, a highly potent and specific binder of B7-H3, characterized it, and advanced it to a development candidate in the fourth quarter of 2024. AKY-2519, a proprietary 49-amino acid rationally designed miniprotein, met all of our pre-specified development candidate criteria including those for potency, selectivity, thermal stability, radiochemical stability, and solubility. AKY-2519 also met or exceeded our desired pharmacokinetic and biodistribution benchmarks while demonstrating robust preclinical efficacy. Preclinical studies of [ 225 Ac]Ac-AKY-2519 As shown below, [ 225 Ac]Ac-AKY-2519 demonstrated dose-dependent antitumor activity after a single administration in mice harboring a non-small cell lung cancer cell, or NSCLC, line-derived xenograft tumor. Mice treated with a [ 225 Ac]Ac-AKY-2519 showed marked tumor growth inhibition of 92% for the 1.0 µCi dose and 80% for the 0.5 µCi dose, compared to vehicle (n=8 mice per group), and a best response of 48% regression at the 1.0 µCi group. The observed tumor growth inhibition led to prolonged survival for mice treated at each dose level compared to vehicle-treated mice. Body weight remained constant throughout the treatment period, suggesting that both dose levels of [ 225 Ac]Ac-AKY-2519 were well tolerated. 22 [ 225 Ac]Ac-AKY-2519 demonstrated antitumor activity and increased survival in xenograft models An analysis of B7-H3 expression across human tumor microarrays demonstrated that B7-H3 is highly expressed in multiple solid tumor indications, specifically squamous NSCLC, squamous esophageal, prostate and triple-negative breast cancers, or TNBC. Levels of B7-H3 expression across these indications are comparable to the level of expression of the mouse model utilized in our preclinical studies, supporting the translational relevance of this model and suggesting that a majority of patients in these indications express equivalent or higher levels of B7-H3 compared to the mouse model that responded robustly to [ 225 Ac]Ac-AKY-2519 treatment. B7-H3 expression across multiple tumor types Our development strategy for [ 225 Ac]Ac-AKY-2519 [ 68 Ga]Ga-AKY-2519 and [ 177 Lu]Lu-AKY-2519 uptake in tumors and normal tissue biodistribution is currently being assessed in patients with various B7-H3 expressing solid tumors. To date, each of [ 68 Ga]Ga-AKY-2519 and [ 177 Lu]Lu-AKY-2519 has demonstrated compelling tumor uptake across different tumor types with low uptake in normal tissues and a differentiated biodistribution profile, showcasing rapid clearance from normal organ and tissues, including the kidney. We expect the results of the imaging and dosimetry assessment in patients with various tumor types to be reported in mid-2026. In March 2026, our INDs for [ 225 Ac]Ac-AKY-2519 and for [ 64 Cu]Cu-AKY-2519 were cleared by the FDA to proceed to a Phase 1b clinical trial. We expect 23 to initiate the multi-site Phase 1b clinical trial mid-2026. We currently anticipate that the Phase 1b program will follow a dose escalation strategy utilizing the BOIN design. The Phase 1b program is planned to enroll patients with mCRPC, NSCLC or small cell lung cancer, using [ 64 Cu]Cu-AKY-2519 for dosimetry and imaging and [ 225 Ac]Ac-AKY-2519 for therapy. Following completion of dose escalation, dose expansions are planned for mCRPC and lung cancers. The primary endpoint will be to assess safety and tolerability of [ 225 Ac]Ac-AKY-2519. Secondary endpoints will include objective response rate (as measured by RECIST v1.1), duration of response, progression-free survival, overall survival, changes in quality of life, and to characterize pharmacokinetic and pharmacodynamic profiles. Competition The development and commercialization of new radiopharmaceutical products is highly competitive. We face and will continue to face competition from third parties that use radiopharmaceuticals and from companies focused on more traditional therapeutic modalities. Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection, and establish collaborative arrangements for research, development, manufacturing, and commercialization of new products. We consider our most direct competitors to be companies developing targeted alpha-based radiopharmaceuticals for the treatment of cancer. There are several companies developing targeted alpha-based radiopharmaceuticals for the treatment of cancer, including Abdera Therapeutics, Actinium Pharmaceuticals, Inc., Alpha9 Oncology, Inc., Artbio AS, Bayer AG, Convergent Therapeutics, Fusion Pharmaceuticals Inc. (acquired by AstraZeneca), Johnson & Johnson, Mariana Oncology, Inc. (acquired by Novartis AG), Perspective Therapeutics, POINT Biopharma Global Inc. (acquired by Eli Lilly), RadioMedix, Inc., Radionetics Oncology, RayzeBio, Inc. (acquired by Bristol Myers Squibb) and Telix Pharmaceuticals Limited. These companies are targeting a wide range of solid and hematologic malignancies using various alpha emitting isotopes, including radium-223, lead-212, and 225 Ac. The first and only approved alpha particle-based therapy is Bayer’s Xofigo (radium-223) which is a salt of radium that cannot easily and robustly be attached to a targeting molecule, but naturally localizes to regions where cancer cells infiltrate bone. Xofigo was approved in 2013 for the treatment of prostate cancer with symptomatic bone metastases. There are several companies with approved beta-emitting radiopharmaceuticals, including Lantheus Holdings, Novartis, Bayer, Sirtex, Boston Scientific and Q BioMed Inc. and other companies developing beta-emitting radiopharmaceuticals, including POINT Biopharma Global (acquired by Eli Lilly), ITM Isotope Technologies Munich SE, Y-Mabs and Telix Pharmaceuticals Limited. The beta emitting isotopes used by these companies include iodine-131, 177 Lu, strontium-89 and yttrium-90. A recently approved beta particle-based radiopharmaceutical is Novartis’ Pluvicto, which was approved by the FDA in 2022 for the treatment of patients with metastatic prostate cancer. Our competitors will also include companies that are or will be developing other treatment methods, including those utilizing other radioisotopes, as well as therapies for the same indications in oncology that we are targeting. In addition to the competitors we face in developing radiopharmaceuticals, we will also face competition in the indications we expect to pursue. To compete effectively with these existing therapies, we will need to demonstrate that our therapies are favorable to existing therapeutics and obtain comparable coverage and reimbursement for our product candidates. Many of our current or future competitors have significantly greater financial resources and expertise in research and development, isotope supply chain logistics, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals, obtaining reimbursement for and marketing of approved products than we do. Mergers and acquisitions in the biotechnology, pharmaceutical and diagnostic industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These competitors also compete with us in recruiting and retaining qualified personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we or our collaborators may develop. Our competitors also may obtain FDA or other foreign regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we or our collaborators are able to enter the market. Even if the product candidates we may develop in the future achieve regulatory approval, they may be priced at a significant premium over competitive products if any have been approved by then, resulting in reduced competitiveness. Moreover, technological advances or products developed by our competitors may render our technologies or product candidates we may develop in the future obsolete, less competitive, or not economical. The key competitive factors affecting the success of [ 225 Ac]Ac-AKY-1189 and our other current and future product candidates, if approved, are likely to be their efficacy, safety, convenience, price, the level of generic competition and the availability of reimbursement from government and other third-party payors. Intellectual property Our success depends in part on our ability to obtain, maintain, protect, defend and enforce proprietary protection for our product candidates and other discoveries, inventions, trade secrets and know-how that are critical to our business operations. Our success 24 also depends in part on our ability to operate without infringing, misappropriating or otherwise violating the intellectual property or proprietary rights of others, and in part on our ability to prevent others from infringing, misappropriating or violating our intellectual property or proprietary rights. A discussion of risks relating to intellectual property is provided under the section titled “Risk factors—Risks related to intellectual property.” With respect to our [ 225 Ac]Ac-AKY-1189 program, as of March 1, 2026, we own one pending international patent application filed under the Patent Cooperation Treaty, or a PCT Application, one issued U.S. patent, one pending U.S. non-provisional utility application and two pending foreign non-provisional patent applications in each of Taiwan and Argentina, which are directed to, among other things, composition of matter and uses of [ 225 Ac]Ac-AKY-1189. We do not own or license, and do not expect to own or license, any patents or patent applications that cover the radioactive payload in [ 225 Ac]Ac-AKY-1189, which is 225 Ac. The issued U.S. patent and any patents issuing from the patent applications we own or future patent applications that we may file based on these applications are expected to expire in 2044, excluding any patent term adjustments or extensions that may be available and assuming timely payment of all appropriate maintenance, renewal, annuity or other governmental fees. With respect to our [ 225 Ac]Ac-AKY-2519 program, as of March 1, 2026, we own one pending PCT Application, one pending U.S. non-provisional utility application, and two pending foreign non-provisional patent applications in each of Taiwan and Argentina, which are directed to, among other things, composition of matter and uses of [ 225 Ac]Ac-AKY-2519. We do not own or license any issued patents related to our [ 225 Ac]Ac-AKY-2519 program. In addition, we do not expect to own or license any patents or patent applications that cover the radioactive payload in [ 225 Ac]Ac-AKY-2519, which is 225 Ac. Any patents issuing from the patent applications we own or future patent applications that we may file based on these applications are expected to expire in 2044, excluding any patent term adjustments or extensions that may be available and assuming timely payment of all appropriate maintenance, renewal, annuity or other governmental fees. With respect to our platform program, as of March 1, 2026, we own one pending PCT Application, 22 pending non-provisional patent applications in each of Australia, Brazil, Canada, Chile, China, Colombia, Eurasia, Europe, Israel, India, Japan, Morocco, Mexico, Peru, Philippines, Saudi Arabia, South Africa, South Korea, Taiwan, Tunisia, United Arab Emirates, and the United States, and one pending U.S. provisional patent application. We do not own or license any issued patents related to our platform program. Any patents that issue from the patent applications we own or future patent applications that we may file based on these applications are expected to expire in 2043, 2045 and 2046, excluding any patent term adjustments or extensions that may be available and assuming timely payment of all appropriate maintenance, renewal, annuity or other governmental fees. With respect to our discovery programs, as of March 1, 2026, we own one pending PCT Application, one pending U.S. provisional patent application, and four non-provisional patent applications (one each in China, Europe, the United States and South Africa), each of which is directed to compositions of matter and uses for miniproteins against our targets of interest. We do not own or license any issued patents related to our discovery programs. Any patents issuing from the patent applications we own or future patent applications that we may file based on these applications are expected to expire in 2043, 2044 and 2046, excluding any patent term adjustments or extensions that may be available and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. U.S. provisional patent applications are not eligible to become issued patents unless and until, among other things, we file one or more non-provisional U.S., foreign, and/or PCT Applications within 12 months of the first-filed provisional application to which these non-provisional applications claim priority. With regard to such U.S. provisional patent applications, if we do not timely file any non-provisional patent applications, we will lose our priority date with respect to subject matter and inventions disclosed in these provisional patent applications. Provided no statutory bars to patentability have occurred during the 12-month pendency of the provisional patent application, the option to refile and obtain a later filing date remains open. While we intend to timely file non-provisional patent applications related to our provisional patent applications, we cannot predict whether any such patent applications will result in the issuance of patents that provide us with any competitive advantage. Further, our PCT Applications are not eligible to become patents until, among other things, we timely file national stage patent applications in jurisdictions that are party to the Patent Cooperation Treaty, and in which we seek patent protection. If we do not timely file any national stage patent applications, we may lose our priority date with respect to our PCT Applications and any patent protection on inventions disclosed in such PCT Applications. The proprietary nature of, and protection for, our product candidates and their methods of use are an important part of our strategy to develop and commercialize novel medicines. We have filed for or licensed patents rights relating to certain of our product candidates and are pursuing additional patent protection for them and for our other product candidates and technologies. In addition to patent protection, we also rely on trade secrets, know-how, trademarks, confidential information, other proprietary information and continuing technological innovation to develop, strengthen and maintain our competitive position. We seek to protect and maintain the confidentiality of proprietary information to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection. Although we take steps to protect our proprietary information and trade secrets, including through contractual means with our employees, consultants, contractors and collaborators, third parties may independently develop substantially equivalent proprietary information and techniques or otherwise gain access to our trade secrets or disclose our technology. Thus, we may not be able to meaningfully protect our trade secrets. It is our policy to require our employees, consultants, outside scientific collaborators, sponsored researchers and other advisors to execute confidentiality and invention assignment agreements upon the commencement of employment or consulting relationships with us. However, such 25 confidentiality agreements can be breached, and we may not have adequate remedies for any such breach. For more information regarding the risks related to our intellectual property, see the section titled “Risk factors—Risks related to intellectual property.” License and collaboration agreements Institute for Protein Innovation License Agreement On November 1, 2021, we and the Institute for Protein Innovation, Inc., or IPI, entered into an Exclusive License Agreement, as amended on July 26, 2022, the IPI Agreement, pursuant to which IPI granted us an exclusive, worldwide license, with the right to sublicense (subject to certain conditions), under certain of IPI’s patents and know-how related to certain binder proteins, targeting up to 14 target proteins, including Nectin-4, to research, develop, make, have made, and commercialize certain products. Pursuant to the IPI Agreement, IPI also granted us a non-exclusive license to certain intellectual property rights required to research, develop, make, have made, and commercialize certain products. Upon execution of the IPI Agreement, we paid an upfront license fee of $0.2 million and are required to pay an annual license fee of less than $0.1 million until the first commercial sale of the first licensed product, pursuant to which we have paid an aggregate of $0.2 million through December 31, 2025. The IPI Agreement requires us to pay up to an aggregate of $24.0 million upon achievement of certain regulatory and development milestones. In addition, if we successfully commercialize a licensed product under the IPI Agreement, we are required to pay low single-digit royalties on net sales, on a product-by-product and country-by-country basis, subject to specified reductions, until the later of (a) the expiration of the last to expire valid claim covering the manufacture, use or sale of such licensed product in such country or (b) ten years after the first licensed product sale in such country. The royalties are subject to specified and capped reductions for payments owed to third parties for additional rights necessary to commercialize licensed products. The IPI Agreement requires us to use diligent and commercially reasonable efforts to develop and commercialize a licensed product. At any time after the fifth year anniversary of the IPI Agreement, if IPI receives a third-party request to license certain rights granted to us pursuant to the IPI Agreement for which we are not actively developing or commercializing a licensed product, we must either (i) submit a commercially reasonable development plan for such undeveloped field to IPI that we will put into effect within a certain number of days, (ii) substantiate why granting a license to such rights in such undeveloped field to the third party is not in our best business interest or (iii) enter into good faith negotiations with such third party for such rights in such undeveloped field. Unless earlier terminated, the IPI Agreement will expire at the end of the last to expire royalty term. IPI may, at its election, either terminate the IPI Agreement, convert any of our exclusive license rights into non-exclusive rights, or choose to reduce the field or territory, if (a) the first commercial sale of a licensed product does not occur by January 1, 2035 or the payment of earned royalties, once begun, ceases for more than eight consecutive calendar quarters; (b) we default in the timely payment of any amount due or are otherwise in breach of the IPI Agreement and fail to remedy such default or breach within 30 days after written notice thereof; (c) we are found, on more than one examination, to have underreported or underpaid any royalty payment by more than five percent in any three calendar quarters in the period under examination; (d) we cease to carry on our business related to the subject matter of the licensed patents or (e) we become insolvent or file a petition regarding bankruptcy or insolvency or other certain insolvency or bankruptcy-related events occur. We may terminate the IPI Agreement in its entirety, with or without cause, upon 60 days’ written notice. TRIUMF License Agreement On July 21, 2022, we and TRIUMF Inc., a Canadian non-profit, or TRIUMF, TRIUMF Innovations, Inc., a Canadian non-profit, the University of British Columbia, and BC Cancer, a provincial health services authority, entered into a License Agreement, the TRIUMF License. Pursuant to the TRIUMF License, TRIUMF, the University of British Columbia and BC Cancer, or the Licensors, granted us a non-exclusive, worldwide license, with right to sublicense (subject to certain conditions), under certain patents and know-how related to the Licensors’ chelator technology to make, use, sell, offer for sale, import, and export certain radiopharmaceutical products for the diagnosis, treatment, amelioration, and prevention of human diseases and conditions. None of our product candidates currently incorporate, or rely on, the licensed patents and know-how from the TRIUMF License. We paid an initial license fee of $0.1 million upon execution of the TRIUMF License. The TRIUMF License requires us to pay up to an aggregate of $2.0 million upon achievement of certain regulatory and development milestones. We are also obligated to pay low single digit royalties on net sales of licensed products, on a product-by-product basis. For licensed products not covered by a valid claim of a licensed patent, our royalty obligation terminates on the tenth anniversary of the first commercial use of such licensed product in each country. Unless earlier terminated, the TRIUMF License will expire on the later of the twelfth-year anniversary of the TRIUMF License or the expiry of the last patent subject to the TRIUMF License. We may terminate the TRIUMF License for convenience upon 60 days’ written notice. The Licensor may, at its option, terminate the TRIUMF License if (i) we become insolvent, cease to carry on business or other certain insolvency or bankruptcy-related events occur, (ii) we breach certain provisions (including those related to sublicenses, confidentiality, and insurance), (iii) the licensed patents and know-how become subject to any security interest, lien, 26 charge or encumbrance in favor of a third party through our action or (iv) there is an uncured breach by our sublicensee and we do not terminate the respective sublicense agreement. Either party may terminate the TRIUMF License for uncured breach, subject to specified cure periods. University of Minnesota License Agreement On March 3, 2023, we and the Regents of the University of Minnesota, or the University of Minnesota, entered into an Exclusive License Agreement, the Minnesota License, pursuant to which the University of Minnesota and the Stanford University, or Stanford, granted us, solely for human and veterinary uses, an exclusive license under the University of Minnesota’s and Stanford’s rights in certain patents related to certain binding proteins to make, use, sell, offer for sale, and import certain therapeutic and diagnostic products in the countries where there are licensed patents and a non-exclusive license to use licensed technical information. None of our product candidates incorporate, or rely on, the patents and know-how from the Minnesota License. We paid an upfront fee of $0.1 million upon entering into the Minnesota License and paid an annual license fee of less than $0.1 million throughout the term of the Minnesota License, pursuant to which we have paid an aggregate of $0.4 million through September 30, 2025. No milestones were achieved under the Minnesota License prior to the termination of this agreement. In July 2025, we provided notice to the University of Minnesota to terminate the Minnesota License and paid the $10,000 early termination fee, with an effective termination date of September 9, 2025. Eli Lilly and Company License, Research and Collaboration Agreement On May 16, 2024, we and Eli Lilly entered into a License, Research and Collaboration Agreement, the Collaboration Agreement. Pursuant to the Collaboration Agreement, we granted Eli Lilly an exclusive (even as to us and our affiliates), royalty-bearing, worldwide license, with the right to sublicense, to certain of our patents and other intellectual property rights to exploit certain compounds and therapeutic or diagnostic products that contain such compounds solely as products that contain a radioactive isotope. We also granted Eli Lilly a non-exclusive, royalty-bearing, worldwide license, with the right to sublicense, to the intellectual property necessary or useful to exploit the licensed compounds and licensed products solely as products that contain a radioactive isotope and a non-exclusive, fully paid-up license, with the right to sublicense, to exploit certain other intellectual property developed under the Collaboration Agreement for any and all purposes (subject to certain limitations). In addition, we and Eli Lilly agreed to negotiate in good faith to enter into a separate agreement in the event the parties agree that the clinical development of a licensed compound requires, or would be benefited by, a license to one of our other compounds. Under the Collaboration Agreement, Eli Lilly may designate a specified number of initial collaboration targets, with the right to substitute other targets. We will be responsible for research activities through initial human imaging studies for a lead candidate for each selected target, and Eli Lilly will thereafter be responsible for regulatory filings, clinical development and commercialization activities worldwide. There is a separate research plan for each collaboration target, and our development costs are capped, on a research plan-by-research plan basis. Eli Lilly will reimburse our reasonable out-of-pocket costs and full-time equivalent costs incurred in excess of the cap. Eli Lilly paid us an upfront license fee of $60.0 million upon execution of the Collaboration Agreement. The Collaboration Agreement requires Eli Lilly to pay up to an aggregate of $525.0 million upon achievement of certain research, development, regulatory and commercial launch milestones and up to an aggregate of $630 million upon achievement of certain sales milestones. In addition, if Eli Lilly successfully commercializes a therapeutic or diagnostic product under the Collaboration Agreement, Eli Lilly is required to pay us tiered royalties of up to 10% based on annual net sales, on a product-by-product and country-by-country basis, subject to specified reductions, until the later of the expiration of licensed patent rights in a country, expiration of regulatory exclusivity, or ten years after the first product sale in such country. The Collaboration Agreement requires Eli Lilly to use commercially reasonable efforts to develop and commercialize a licensed product from a research program in certain markets and through satisfaction of certain criteria. Unless earlier terminated, the Collaboration Agreement will continue on a licensed product-by-licensed product and country-by-country basis until the expiration of the applicable royalty term for such licensed product. Either party may terminate the Collaboration Agreement for uncured material breach, subject to specified cure periods. In certain instances, if Eli Lilly has the right to terminate the Collaboration Agreement for our uncured material breach, Eli Lilly may, at its option, continue the Collaboration Agreement where all payments due from Eli Lilly to us, on a prospective basis, will be reduced by a specified percentage and Eli Lilly diligence and reporting obligations will end. Eli Lilly may, at any time and without cause, terminate the Collaboration Agreement in its entirety or on a collaboration target-by-collaboration target or region-by-region basis upon sixty days’ notice. In connection with the Collaboration Agreement, we and Eli Lilly entered into a Series A-1 redeemable convertible preferred stock purchase agreement pursuant to which we issued and sold an aggregate of 2,500,000 shares of our Series A-1 redeemable convertible preferred stock at a purchase price of $4.00 per share for aggregate net proceeds of $10.0 million. 27 Government regulation Government authorities in the U.S., including federal, state, and local authorities, and in other countries, extensively regulate, among other things, the manufacturing, research and clinical development, marketing, labeling and packaging, storage, distribution, post-approval monitoring and reporting, advertising and promotion, and export and import of biological products, such as those we are developing. In addition, some government authorities regulate the pricing of such products. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local, and foreign statutes and regulations require the expenditure of substantial time and financial resources. Review and approval for licensing biologics in the U.S. In the U.S., the FDA regulates biological products under the Federal Food, Drug, and Cosmetic Act, or the FDCA, the Public Health Service Act, or the PHSA, and their implementing regulations. FDA approval is required before any biological product can be marketed in the U.S. Biological products are also subject to other federal, state, and local statutes and regulations. If we fail to comply with applicable FDA or other requirements at any time during the product development process, clinical testing, the approval process or after approval, we may become subject to administrative or judicial sanctions or other consequences, including the FDA’s refusal to allow us to proceed with clinical testing, issuance of clinical holds for planned or ongoing studies, refusal to approve pending applications, license suspension or revocation, withdrawal of an approval, issuance of untitled or warning letters, product recalls, product seizures, import detentions or refusals, total or partial suspension of manufacturing or distribution, injunctions, fines, civil penalties or criminal prosecution. Any such action could have a material adverse effect on us. The process required by the FDA before product candidates may be marketed in the U.S. generally involves the following: • completion of extensive nonclinical laboratory tests and nonclinical animal studies in compliance with applicable good laboratory practices, or GLP, requirements; • submission to the FDA of an IND application, which must become effective before human clinical trials may begin in the U.S. and must be updated annually; • approval by an independent institutional review board, IRB, or ethics committee representing each clinical site before each clinical trial may be initiated; • performance of adequate and well-controlled human clinical trials in accordance with good clinical practices, or GCPs, to establish the safety and efficacy of the product candidate for each proposed indication; • manufacture of the drug substance and drug product in accordance with the FDA’s cGMP requirements, along with required analytical and stability testing; • preparation of and submission to the FDA of a biologics license application, or BLA, requesting marketing approval for one or more proposed indications, that includes sufficient evidence of establishing the safety, purity and potency of the proposed biological product for its intended indication, including from results of nonclinical testing and clinical trials; • review of the product application by an FDA Advisory Committee, where appropriate and if applicable; • a determination by the FDA within 60 days of its receipt of a BLA to file the application for review; • satisfactory completion of one or more FDA pre-approval inspections of the manufacturing facility or facilities where the proposed product is produced to assess compliance with cGMPs and to assure that the facilities, methods, and controls are adequate to preserve the product’s identity, quality, and strength; • satisfactory completion of any FDA audits of the nonclinical studies and clinical trial sites to assure compliance with GLPs and GCPs, as applicable, and the integrity of data in support of the BLA; • payment of user fees under the Prescription Drug User Fee Act, or the PDUFA, unless exempted; and • the FDA’s review and approval of the BLA. The nonclinical and clinical testing and approval process requires substantial time, effort, and financial resources, and we cannot be certain that any approvals for our product candidates will be granted on a timely basis, if at all. Nonclinical studies and investigational New Drug Application Before testing any biological product in humans, a product candidate must undergo rigorous preclinical testing. Preclinical studies include laboratory evaluations of product chemistry, formulation, and stability, as well as in vitro and animal studies to assess safety and in some cases to establish the rationale for therapeutic use. The conduct of preclinical studies is subject to federal and state regulation and requirements, including GLP requirements for safety/toxicology studies. The results of the preclinical studies, together with manufacturing information and analytical data, must be submitted to the FDA as part of an IND. An IND is a request for authorization from the FDA to administer an investigational biological product to humans in clinical trials in the U.S. The central focus of an IND submission is on the general investigational plan, the protocol(s) for human trials and the safety of trial participants. The IND also includes results of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology, and pharmacodynamic characteristics of the product; chemistry, manufacturing and controls 28 information; and any available human data or literature to support the use of the investigational product. An IND must become effective before human clinical trials may begin. An IND will automatically become effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns or questions related to the proposed clinical trials. In such a case, the IND may be placed on clinical hold and the IND sponsor and the FDA must resolve any outstanding concerns or questions before clinical trials can begin. Accordingly, submission of an IND may or may not result in the FDA allowing clinical trials to commence. At any time during the initial 30 day IND review period or while clinical trials are ongoing under the IND, the FDA may impose a partial or complete clinical hold. Clinical holds may be imposed by the FDA when there is concern for patient safety, and may be a result of new data, findings, or developments in clinical, nonclinical, and/or chemistry, manufacturing and controls or where there is non-compliance with regulatory requirements. A clinical hold would delay either a proposed clinical trial or cause suspension of an ongoing trial, until all outstanding concerns have been adequately addressed and the FDA has notified the company that investigations may proceed. A separate submission to an existing IND must also be made for each successive clinical trial to be conducted, and the FDA must grant permission, either explicitly or implicitly by not objecting, before each clinical trial can begin. Clinical trials Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCPs, which include the requirement that all research subjects provide their informed consent for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, the inclusion and exclusion criteria, the parameters to be used in monitoring safety, and the efficacy criteria to be evaluated. A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND. Additionally, approval must also be obtained from each clinical trial site’s IRB, before the trials may be initiated and the IRB must monitor the trial until completed. The IRB will consider, among other things, clinical trial design, patient informed consent, ethical factors, the safety of human subjects and the possible liability of the institution. There are also requirements governing the reporting of ongoing clinical trials and clinical trial results to public registries, including on clinicaltrials.gov. The clinical investigation of a biological product is generally divided into three or four phases. Although the phases are usually conducted sequentially, they may overlap or be combined. Phase 1. The investigational product is initially introduced into healthy human subjects or, in the case of some products designed to address severe or life-threatening diseases, patients with the target disease or condition. These trials are designed to evaluate the safety, dosage tolerance, metabolism and pharmacologic actions of the investigational product in humans, the side effects associated with increasing doses, and if possible, to gain early evidence on effectiveness. Phase 2. The investigational product is administered to a limited patient population to evaluate dosage tolerance and optimal dosage, identify possible adverse side effects and safety risks, and preliminarily evaluate efficacy. Phase 3. The investigational product is administered to an expanded patient population, generally at geographically dispersed clinical trial sites to generate enough data to statistically evaluate safety, purity and potency, to evaluate the overall benefit-risk profile of the investigational product, and to provide an adequate basis for physician labeling. Phase 4. In some cases, the FDA may condition approval of a BLA for a product candidate on the sponsor’s agreement to conduct additional clinical trials after approval or a sponsor may voluntarily conduct additional clinical trials after approval to gain more information about the biological product. Such post-approval trials are typically referred to as Phase 4 clinical trials. Sponsors must also report to the FDA, within certain timeframes, serious and unexpected adverse reactions, any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator’s brochure, or any findings from other studies or animal or in vitro testing that suggest a significant risk in humans exposed to the product candidate. The FDA, the IRB, or the clinical trial sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects are being exposed to an unacceptable health risk. Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data and safety monitoring board or committee. This group provides authorization for whether or not a trial may move forward at designated check points based on access to certain data from the trial. We may also suspend or terminate a clinical trial based on evolving business objectives or competitive climate. A sponsor of an investigational biological product for a serious disease or condition 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 biological product. This requirement applies on the earlier of the first initiation of a Phase 2 or Phase 3 trial of the investigational biological product or, as applicable, 15 days after the biological product receives a designation as a breakthrough therapy or fast track product. Concurrent with clinical trials, sponsors usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the product candidate and finalize a process for manufacturing the drug product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the product candidate and manufacturers must develop, among other things, methods for testing the identity, strength, quality, and purity of the final drug product. Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life. 29 During the development of a new biologic, sponsors are given opportunities to meet with the FDA at certain points. These points may be prior to submission of an IND, at the end of Phase 1, at the end of Phase 2, and before a BLA is submitted. Meetings at other times may be requested. These meetings can provide an opportunity for the sponsor to share information about the data gathered to date, for the FDA to provide advice, and for the sponsor and the FDA to reach agreement on the next phase of development. Submission of a BLA to the FDA Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, detailed investigational product information is submitted to the FDA in the form of a BLA requesting approval to market the product for one or more indications. Under federal law, the submission of most BLAs is subject to an application user fee, and the sponsor of an approved BLA is also subject to an annual program fee for each approved biological product on the market. Applications for orphan drug products are exempted from the BLA application fee and may be exempted from program fees, unless the application includes an indication for other than a rare disease or condition. A BLA must include all relevant data available from pertinent nonclinical studies and clinical trials, including negative or ambiguous results as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls, and proposed labeling, among other things. Data can come from company-sponsored clinical trials intended to test the safety and effectiveness of a use of a product, or from a number of alternative sources, including trials initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and effectiveness of the investigational product to the satisfaction of the FDA. The FDA conducts a preliminary review of all BLAs within the first 60 days after submission before accepting them for filing to determine whether they are sufficiently complete to permit substantive review. The FDA may request additional information rather than accept an application for filing. Under the performance goals and policies implemented by the FDA under PDUFA, once a BLA has been submitted, the FDA’s goal for novel biological products generally is to review the application within ten months after it accepts the application for filing, or, if the application is granted priority review, six months after the FDA accepts the application for filing. The FDA does not always meet its PDUFA goal dates, and the review process may be extended. For example, the review process and the PDUFA goal date may be extended by three months if the FDA requests or if the applicant otherwise provides additional data, analysis or information that FDA deems a major amendment. Before approving a BLA, the FDA typically will inspect the facility or facilities where the product is manufactured. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving a BLA, the FDA will typically inspect the sponsor and one or more clinical sites to assure compliance with GCPs. Material changes in manufacturing equipment, location, or process post-approval, may result in additional regulatory review and approval. 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 a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates and provides a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. The FDA’s decision on a BLA On the basis of the FDA’s evaluation of the application and accompanying information, including the results of the inspection of the manufacturing facilities and any FDA inspections of nonclinical and clinical trial sites to assure compliance with GLPs or GCPs, the FDA may approve the BLA or issue a complete response letter. Under the PHSA, the FDA may approve a BLA if it determines the product is safe, pure, and potent, and that the facility in which the product will be manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, purity and potency. If the FDA determines the product meets those standards, it may issue an approval letter authorizing commercial marketing of the biological product with specific prescribing information for specific indications. If the application is not approved, FDA will issue a complete response letter, which indicates that the review cycle of the application is complete and the application is not ready for approval. A complete response letter will identify the deficiencies that prevent the FDA from approving the application and may require additional clinical data or an additional Phase 3 clinical trial(s), or other significant, expensive and time-consuming requirements related to clinical trials, nonclinical studies or manufacturing. Even if such additional information is submitted, the FDA may ultimately decide that the BLA does not satisfy the criteria for approval and issue a denial. 30 The FDA could also approve the BLA with a Risk Evaluation and Mitigation Strategy, or REMS, program to mitigate risks, which 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. The FDA also may condition approval on, among other things, changes to proposed labeling, development of adequate controls and specifications, or a commitment to conduct one or more post-market studies or clinical trials. Such post-market testing may include Phase 4 clinical trials and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization. Orphan drug designation 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, which is generally a disease or condition that affects fewer than 200,000 individuals in the U.S., or more than 200,000 individuals in the U.S. and for which there is no reasonable expectation that the cost of developing and making a drug or biological product available in the U.S. for this type of disease or condition will be recovered from sales of the product. Orphan product designation must be requested before submitting a BLA. After the FDA grants orphan product designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review and approval process. 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. Additionally, if a product that has orphan designation subsequently receives the first FDA approval for the disease or condition 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 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 exclusivity. The period of exclusivity begins on the date that the marketing application is approved by the FDA and applies only to the indication for which the product has been designated. The FDA may approve a second application for the same product for a different use or a second application for a clinically superior version of the product for the same use. The FDA cannot, however, approve the same product made by another manufacturer for the same indication during the market exclusivity period unless it has the consent of the sponsor, or the sponsor is unable to provide sufficient quantities. If a drug or biological product designated as an orphan product receives marketing approval for an indication broader than what is designated, it may not be entitled to orphan product exclusivity. Orphan drug status in the European Union has similar, but not identical, benefits. The FDA has historically taken the position that the scope of orphan exclusivity aligns with the approved indication or use of a product, rather than the disease or condition for which the product received orphan designation. However, in Catalyst Pharms., Inc. v. Becerra , 14 F.4th 1299 (11th Cir. 2021), the court disagreed with this position, holding that orphan-drug exclusivity blocked the FDA’s approval of the same drug for all uses or indications within the same orphan-designated disease. On January 24, 2023, the FDA published a notice in the Federal Register to clarify that the FDA intends to continue to apply its longstanding interpretation of the regulations to all matters outside of the scope of the Catalyst order and will continue tying the scope of orphan-drug exclusivity to the uses or indications for which a drug is approved. It is unclear how future litigation, legislation, agency decisions, and administrative actions will impact the scope of orphan drug exclusivity. Expedited review programs The FDA offers a number of expedited development and review programs for qualifying product candidates. New biological products are eligible for fast track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition. Fast track designation applies to the combination of the product and the specific indication for which it is being studied. The sponsor of a new biologic may request that the FDA designate the biologic as a fast track product at any time during the clinical development of the product. The sponsor of a fast track product has opportunities for more frequent interactions with the applicable FDA review team during product development and, once a BLA is submitted, the product candidate may be eligible for priority review. A fast track product may also be eligible for rolling review, where the FDA may consider for review sections of the BLA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the BLA, the FDA agrees to accept sections of the BLA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the BLA. A product candidate intended to treat a serious or life-threatening disease or condition may also be eligible for breakthrough therapy designation to expedite its development and review. A product candidate can receive breakthrough therapy designation if preliminary clinical evidence indicates that the product candidate, alone or in combination with one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. The designation includes all of the fast track program features, as well as more intensive FDA interaction and guidance beginning as early as Phase 1 and an organizational commitment to expedite the development and review of the product candidate, including involvement of senior managers. 31 Any marketing application for a biologic submitted to the FDA for approval, including a product candidate with a fast track designation and/or breakthrough therapy designation, may be eligible for other types of FDA programs intended to expedite development and review, such as priority review. An application for a biological product will receive priority review designation if it is for a biological product that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness. The FDA will attempt to direct additional resources to the evaluation of an application for a new biological product designated for priority review in an effort to facilitate the review. For original BLAs, priority review designation means the FDA’s goal is to take action on the marketing application within six months of the 60-day filing date (as compared to ten months under standard review). Fast track designation, breakthrough therapy designation, and priority review do not change the standards for approval but may expedite the development or approval process. Even if a product candidate qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened. Accelerated approval Product candidates studied for their safety and effectiveness in treating serious conditions may receive accelerated approval upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments. As a condition of accelerated approval, the FDA will generally require the sponsor to perform adequate and well-controlled post-marketing clinical studies to verify and describe the anticipated effect on irreversible morbidity or mortality or other clinical benefit. Under the Food and Drug Omnibus Reform Act of 2022, or FDORA, the FDA may require, as appropriate, that such trials be underway prior to approval or within a specific time period after the date of approval for a product granted accelerated approval. Under FDORA, the FDA has increased authority for expedited procedures to withdraw approval of a biologic or indication approved under accelerated approval if, for example, the sponsor fails to conduct the required post-marketing studies or if such studies fail to verify the predicted clinical benefit. In addition, for products being considered for accelerated approval, the FDA generally requires, unless otherwise informed by the FDA, that all advertising and promotional materials intended for dissemination or publication within 120 days of marketing approval be submitted to FDA for review during the pre-approval period. After 120 days following marketing approval, unless otherwise informed by the FDA, advertising and promotional materials must be submitted at least 30 days prior to the intended time of initial dissemination or publication. Project Optimus In 2021, the FDA’s Oncology Center of Excellence launched Project Optimus, an initiative to reform the dose optimization and dose selection paradigm in oncology drug development to emphasize selection of an optimal dose, which is a dose that maximizes not only the efficacy of a drug but also its safety and tolerability. Project Optimus was driven by the FDA’s concerns that the historical approach to dose selection, which generally determined the maximum tolerated dose, may have resulted in doses and schedules of molecularly targeted therapies that were inadequately characterized before the initiation of pivotal trials. Project Optimus requires the implementation of strategies for dose finding and dose optimization that leverage nonclinical and clinical data in dose selection, including randomized evaluations of a range of doses in trials. This initiative emphasizes the performance of dose finding and dose optimization studies as early and efficiently as possible in development programs. In support of this initiative, the FDA may request sponsors of oncology product candidates to conduct dose optimization studies. Post-approval requirements Biological products manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to recordkeeping, periodic reporting, product sampling and distribution, advertising and promotion and reporting of adverse experiences with the product. After approval, most changes to the approved product, such as adding new dosage forms, indications or other labeling claims, are subject to prior FDA review and approval. 32 Biological product manufacturers are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections for compliance with cGMPs. Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon us and any third-party manufacturers that we may decide to use. Manufacturers and manufacturers’ facilities are also required to comply with applicable product tracking and tracing requirements and notify the FDA of counterfeit, diverted, stolen and intentionally adulterated products or products that are otherwise unfit for distribution in the U.S. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance. A biological product may also be subject to official lot release, meaning that 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 lot release, the manufacturer must submit samples of each lot, together with a release protocol showing a summary of the history of manufacture of the lot and the results of all of the manufacturer’s tests performed on the lot, to the FDA. The FDA may perform certain confirmatory tests on lots of some products before releasing the lots for distribution. Until we are able to establish our own cGMP manufacturing facility, we expect to continue to rely on third parties for the production of clinical quantities of our product candidates, and expect to rely in the future on third parties for the production of commercial quantities. Future FDA and state inspections may identify compliance issues at our facilities or at the facilities of our contract manufacturers that may disrupt production, or distribution, or may require substantial resources to correct. In addition, discovery of previously unknown problems with a product or the failure to comply with applicable requirements may result in restrictions on a product, manufacturer or holder of an approved BLA, including withdrawal or recall of the product from the market or other voluntary, FDA-initiated or judicial action that could delay or prohibit further marketing. The FDA may suspend or revoke product license approvals if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical trials to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. FDA has authority to require post-market studies, in certain circumstances, on reduced effectiveness of a biological product and FDA may require labeling changes related to new reduced effectiveness information. Other potential consequences of a failure to maintain regulatory compliance include, among other things: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • issuance of safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; • untitled letters or warning letters; • imposition of clinical holds on ongoing clinical trials; • refusal of the FDA to approve pending BLAs or supplements to approved BLAs, or suspension or revocation of approved BLAs; • product seizure or detention, or refusal to permit the import or export of products; • mandated modification of promotional materials and labeling, and the issuance of corrective information; • consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs; or • fines, injunctions or the imposition of civil or criminal penalties. The FDA strictly regulates marketing, labeling, advertising, and promotion of prescription drug products, including biological products. These regulations include, among other things, standards and regulations for direct-to- consumer advertising, communications regarding unapproved uses, industry-sponsored scientific and educational activities and promotional activities involving the internet and social media. Promotional claims about a drug’s safety or effectiveness are prohibited before the BLA is approved. Once a BLA is approved, the sponsor can only make those claims relating to safety, efficacy, purity and potency that are consistent with the biological product’s approved label. Additionally, promotional materials for prescription drug products must be submitted to the FDA in conjunction with their first use. 33 In the U.S., healthcare professionals are generally permitted to prescribe legally available drugs for uses that are not described in the product’s labeling and that differ from those approved by the FDA. The FDA does not regulate the practice of medicine or healthcare providers’ choice of treatments; however, FDA restricts manufacturers’ communications of off-label uses. If a company, including any agent of the company or anyone speaking on behalf of the company, is found to have promoted off-label uses, the company may become subject to adverse public relations and administrative and judicial enforcement by the FDA, the DOJ, or the Office of the Inspector General of HHS, as well as state authorities. This could subject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner in which a company promotes or distributes drug products. The federal government has levied large civil and criminal fines against companies for alleged improper promotion and has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed. Pediatric trials and exclusivity Under the Pediatric Research Equity Act of 2003, a BLA (or BLA supplement thereto) must contain data that are adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. A sponsor who is planning to submit a marketing application for a biological product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration must submit an initial Pediatric Study Plan, or PSP, within sixty days of an end of Phase 2 meeting or as may be agreed between the sponsor and FDA. The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including study objectives and design, age groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information. Generally, development program candidates designated as orphan drugs are exempt from the above requirements. FDA and the sponsor must reach agreement on the PSP. A sponsor can submit amendments to an agreed upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from nonclinical studies, early phase clinical trials, and/or other clinical development programs. The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data requirements. The FDA may send a non-compliance letter to any sponsor that fails to submit the required assessment, keep a deferral current or fails to submit a request for approval of a pediatric formulation. Unless otherwise required by regulation, the pediatric data requirements do not apply to products with orphan designation. Pediatric exclusivity is another type of non-patent exclusivity in the U.S. and, if granted for a biologic, provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity for all formulations, dosage forms, and indications of the biologic, including the five-year and three-year non-patent and orphan exclusivity. This six-month exclusivity may be granted if a BLA sponsor submits pediatric data that fairly respond to a written request from the FDA for such data, provided that at the time pediatric exclusivity is granted there is not less than nine months of term remaining. The data do not need to show the product to be effective in the pediatric population studied; rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted. If reports of FDA-requested pediatric trials are submitted to and accepted by the FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity or patent protection covering the product are extended by six months. This is not a patent term extension, but it effectively extends the regulatory period during which the FDA cannot accept or approve another application relying on the BLA sponsor’s data. Patent term restoration Depending upon the timing, duration, and specifics of the FDA approval of the use of our product candidates, some of our 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. However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date. The patent term restoration period is generally one-half the time between the effective date of an IND and the submission date of a BLA, plus the time between the submission date and the approval of that application. Only one patent applicable to an approved product is eligible for the 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. In the future, we may apply for restoration of patent term for one of our currently owned or licensed patents to add patent life beyond its current expiration date, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant BLA. 34 Regulation of diagnostic patient selection tool We believe that the success of certain of our product candidates may depend, in part, on the development and commercialization of an imaging agent that will serve, where needed, as a patient selection tool. This diagnostic imaging agent is subject to FDA regulation, review, and approval in the same manner as the therapeutic biological products we are seeking to develop and commercialize and are subject to the same risks. 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, or CMS, other divisions of the Department of Health and Human Services, or HHS, 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. European Union/rest of world government regulation In addition to regulations in the U.S., we will be subject to a variety of regulations in other jurisdictions governing, among other things, clinical trials and any commercial sales and distribution of our products. The cost of establishing a regulatory compliance system for numerous varying jurisdictions can be very significant. Although many of the issues discussed above with respect to the United States apply similarly in the context of the European Union and in other jurisdictions, the approval process varies between countries and jurisdictions and can involve additional product testing and additional administrative review periods. The time required to obtain approval in other countries and jurisdictions might differ from and be longer than that required to obtain FDA approval. Regulatory approval in one country or jurisdiction does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country or jurisdiction may negatively impact the regulatory process in others. Whether or not we obtain FDA approval for a product, we must obtain the requisite approvals from regulatory authorities in foreign countries prior to the commencement of clinical trials or marketing of the product in those countries. Certain countries outside of the United States have a similar process that requires the submission of a clinical trial application much like the IND prior to the commencement of human clinical trials. In the European Union, for example, a clinical trial authorization application must be submitted for each clinical protocol to each country’s national health authority and an independent ethics committee, much like the FDA and IRB, respectively. Under the EU Clinical Trials Regulation, this is now done through a single application submitted through the Clinical Trials Information System, or CTIS, as described in more detail below. The requirements and process governing the conduct of clinical trials vary from country to country. In all cases, the clinical trials are conducted in accordance with GCP, the applicable regulatory requirements, and the ethical principles that have their origin in the Declaration of Helsinki. To obtain regulatory approval of a medicinal product under European Union regulatory systems, we must submit a marketing authorization application. The content of the BLA filed in the U.S. is similar to that required in the European Union, with the exception of, among other things, country-specific document requirements. For other countries outside of the European Union, such as countries in Eastern Europe, Latin America or Asia, the requirements governing product licensing, pricing, and reimbursement vary from country to country. Countries that are part of the European Union, as well as countries outside of the European Union, have their own governing bodies, requirements, and processes with respect to the approval of biological products. If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution. Clinical trial approval in the European Union In April 2014, the European Union adopted the Clinical Trials Regulation (EU) No 536/2014, which replaced the Clinical Trials Directive 2001/20/EC on January 31, 2022. The Clinical Trials Regulation is directly applicable in all European Union Member States meaning no national implementing legislation in each European Union Member State is required. The Clinical Trials Regulation aims to simplify and streamline the approval of clinical trials in the European Union. The main characteristics of the regulation include: a streamlined application procedure via a single-entry point, through the CTIS; a single set of documents to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors; and a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts (Part I contains scientific and medicinal product documentation and Part II contains the national and patient-level documentation). Part I is assessed by a coordinated review by the competent authorities of all European Union Member States in which an application for authorization of a clinical trial has 35 been submitted (Member States concerned) of a draft report prepared by a reference Member State. Part II is assessed separately by each Member State concerned. Strict deadlines have also been established for the assessment of clinical trial applications. Marketing authorization procedures in the European Union Medicines can be authorized in the European Union by using either the centralized authorization procedure or national authorization procedures. The European Commission implemented the centralized procedure for the approval of human medicines to facilitate marketing authorizations that are valid throughout the European Economic Area, or the EEA, which is comprised of the Member States of the European Union plus Norway, Iceland, and Lichtenstein. The centralized procedure is administered by the European Medicines Agency, or EMA, and is compulsory for human medicines that are: derived from certain biotechnology processes, such as genetic engineering, contain a new active substance indicated for the treatment of certain diseases, such as HIV, AIDS, cancer, diabetes, neurodegenerative disorders or autoimmune diseases and other immune dysfunctions, advanced therapy medicines (gene therapy, somatic cell therapy or tissue-engineered medicines), and officially designated orphan medicines. For medicines that do not fall within these categories, an applicant has the option of submitting an application for a centralized marketing authorization to the EMA, as long as the medicine concerned contains a new active substance not yet authorized in the European Union, is a significant therapeutic, scientific or technical innovation, or if its authorization would be in the interest of public health in the European Union. Under the centralized procedure, the EMA’s Committee for Medicinal Products for Human Use, or the CHMP, is responsible for conducting the initial assessment of a product and for several post-authorization and maintenance activities, such as the assessment of modifications or extensions to an existing marketing authorization. Under the centralized procedure in the European Union, the maximum timeframe for the evaluation of a marketing authorization application is 210 days (excluding clock stops, when additional written or oral information is to be provided by the applicant in response to questions asked by the CHMP). Clock stops may extend the timeframe of evaluation of a marketing authorization application considerably beyond 210 days. Where the CHMP gives a positive opinion, it provides the opinion together with supporting documentation to the European Commission, who makes the final decision to grant a marketing authorization, which is issued within 67 days of receipt of the EMA’s recommendation. Accelerated evaluation might be granted by the CHMP in exceptional cases, when a medicinal product is expected to be of a major public health interest, particularly from the point of view of therapeutic innovation. In this circumstance, the EMA ensures that the opinion of the CHMP is given within 150 days, excluding clock stops, but it is possible that the CHMP can revert to the standard time limit for the centralized procedure if it considers that it is no longer appropriate to conduct an accelerated assessment. Prior to obtaining a marketing authorization in the European Union, applicants must demonstrate compliance with all measures included in an EMA-approved pediatric investigation plan, or PIP, covering all subsets of the pediatric population, unless the EMA has granted a product-specific waiver, a class waiver, or a deferral for one or more of the measures included in the PIP. The Pediatric Committee of the EMA, or the PDCO, may grant deferrals for some medicines, allowing a company to delay development of the medicine for children until there is enough information to demonstrate its effectiveness and safety in adults. The PDCO may also grant waivers when development of a medicine for children is not needed or is not appropriate, such as for diseases that only affect the elderly population. Data and market exclusivity in the European Union In the European Union, innovative medicinal products approved on the basis of a complete and independent data package qualify for eight years of data exclusivity upon marketing authorization and an additional two years of market exclusivity. This data exclusivity, if granted, prevents regulatory authorities in the European Union from referencing the innovator’s pre-clinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization in the European Union, during a period of eight years from the date on which the reference product was first authorized in the European Union. Reform of the regulatory framework in the European Union The European Commission introduced legislative proposals in April 2023 that, if implemented, will replace the current regulatory framework in the European Union for all medicines (including those for rare diseases and for children). The European Commission has provided the legislative proposals to the European Parliament and the European Council for their review and approval and, in April 2024, the European Parliament proposed amendments to the legislative proposals. Once the European Commission’s legislative proposals are approved (with or without amendment), they will be adopted into European Union law. The aforementioned European Union rules are generally applicable in the EEA. 36 Brexit and the Regulatory Framework in the United Kingdom The United Kingdom, or UK, formally left the European Union on January 31, 2020, and the European Union and the UK have concluded a trade and cooperation agreement, or TCA, which was provisionally applicable since January 1, 2021 and has been formally applicable since May 1, 2021. The TCA includes specific provisions concerning pharmaceuticals, which include the mutual recognition of cGMP, inspections of manufacturing facilities for medicinal products and cGMP documents issued, but does not provide for wholesale mutual recognition of UK and EU pharmaceutical regulations. At present, Great Britain has implemented European Union legislation on the marketing, promotion and sale of medicinal products through the Human Medicines Regulations 2012 (as amended) (under the Northern Ireland Protocol, the European Union regulatory framework currently continues to apply in Northern Ireland). The regulatory regime in Great Britain therefore aligns in many ways with current European Union regulations, however it is likely that these regimes will diverge significantly in the future now that Great Britain’s regulatory system is independent from the European Union and the TCA does not provide for mutual recognition of UK and European Union pharmaceutical legislation. However, notwithstanding that there is no wholesale recognition of European Union pharmaceutical legislation under the TCA, under a new international recognition procedure which was put in place by the Medicines and Healthcare products Regulatory Agency, or the MHRA, on January 1, 2024, the MHRA may take into account decisions on the approval of a marketing authorization from the EMA (and certain other regulators) when considering an application for a Great Britain marketing authorization. On February 27, 2023, the UK government and the European Commission announced a political agreement in principle to replace the Northern Ireland Protocol with a new set of arrangements, known as the “Windsor Framework”. This new framework fundamentally changes the existing system under the Northern Ireland Protocol, including with respect to the regulation of medicinal products in the UK. In particular, the MHRA will be responsible for approving all medicinal products destined for the UK market (i.e., Great Britain and Northern Ireland), and the EMA will no longer have any role in approving medicinal products destined for Northern Ireland. A single UK-wide marketing authorization will be granted by the MHRA for all medicinal products to be sold in the UK, enabling products to be sold in a single pack and under a single authorization throughout the UK. The Windsor Framework was approved by the EU-UK Joint Committee on March 24, 2023, so the UK government and the European Union will enact legislative measures to bring it into law. On June 9, 2023, the MHRA announced that the medicines aspects of the Windsor Framework will apply from January 1, 2025. Pharmaceutical coverage, pricing and reimbursement In the U.S. and foreign markets, sales of any products for which we may receive regulatory approval for commercial sale will depend in part on the availability of coverage and reimbursement for our products from third-party payors, such as government healthcare programs (e.g., Medicare, Medicaid), managed care organizations, private health insurers, health maintenance organizations, and other organizations. These third-party payors decide which medications they will pay for and will establish reimbursement levels. The availability of coverage and extent of reimbursement by governmental and other third-party payors is essential for patients depending on government or commercial insurance to pay for the costs of prescription medications and other medical products. In the U.S., the principal decisions about reimbursement for new medicines are typically made by the CMS, an agency within the HHS. CMS decides whether and to what extent products will be covered and reimbursed under Medicare and private payors tend to follow CMS to a substantial degree. 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. Factors payors consider in determining reimbursement are based on 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. Our ability to successfully commercialize our product candidates will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from third-party payors, including government healthcare programs (e.g., Medicare, Medicaid), managed care organizations, private health insurers, health maintenance organizations, and other organizations. Moreover, a payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved. In the U.S., no uniform policy of coverage and reimbursement for drug products exists among third-party payors. Therefore, coverage and reimbursement for drug products can 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, and the level of coverage and reimbursement can differ significantly from payor to payor. Third-party payors are increasingly challenging pharmaceutical prices and examining the medical necessity and cost- effectiveness of medical products and services, in addition to their safety and efficacy. 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 37 products, in addition to the costs required to obtain FDA or comparable regulatory approvals. Additionally, we may also need to provide discounts to purchasers, private health plans or government healthcare programs. Our product candidates 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 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. A decision by a third-party payor not to cover a product could reduce utilization once the product is approved and have a material adverse effect on sales, our operations and financial condition. Further, 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. A payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved. Even if we obtain coverage for a given product, the resulting reimbursement payment rates might not be adequate for us to achieve or sustain profitability or may require co-payments that patients find unacceptably high. There is significant uncertainty related to insurance coverage and reimbursement of newly approved products. It is difficult to predict at this time what third-party payors will decide with respect to the coverage and reimbursement for our product candidates. Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and impacted by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the U.S. In addition, many pharmaceutical manufacturers must calculate and report certain price reporting metrics to the government, such as average sales price and best price. Penalties may apply in some cases when such metrics are not submitted accurately and timely. The marketability of any product candidates for which we receive regulatory approval for commercial sale may suffer if third-party payors fail to provide adequate coverage and reimbursement. In addition, emphasis on managed care in the U.S. has increased and could increase the pressure on pharmaceutical pricing. Coverage policies and third-party reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future. Other U.S. Healthcare Laws Healthcare providers, physicians, and third-party payors will play a primary role in the recommendation and prescription of drug products for which we obtain marketing approval. Arrangements with third-party payors, healthcare providers and physicians, as well as patients and other third parties, in connection with the clinical research, sales, marketing and promotion of products, once approved, and related activities, may expose a pharmaceutical manufacturer to broadly applicable fraud and abuse and other healthcare laws and regulations. In the U.S., these laws include, without limitation, state and federal anti-kickback, false claims, transparency, consumer protection, and patient data privacy and cybersecurity laws and regulations, including but not limited to those described below: • The Anti-Kickback Statute, or AKS, makes it illegal for any person or entity, including a prescription drug manufacturer (or a party acting on its behalf) to knowingly and willfully solicit, receive, offer or pay any remuneration (including any kickback, bribe, or rebate), directly or indirectly, overtly or covertly, in cash or in kind, that is intended to induce or reward, referrals including the purchase, recommendation, order or prescription of a particular drug for which payment may be made, in whole or in part, under a federal healthcare program, such as the Medicare and Medicaid programs. The term “remuneration” has been broadly interpreted to include anything of value. The AKS has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand and prescribers, purchasers, patients, and formulary managers on the other. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. Further, courts have found that if “one purpose” of remuneration is to induce referrals, the AKS is violated. In addition, the government may assert that a claim including items or services resulting from a violation of the AKS constitutes a false or fraudulent claim for purposes of the federal False Claims Act, or FCA. • The federal civil and criminal false claims laws, including the FCA, impose criminal and civil penalties against individuals or entities for, among other things, knowingly presenting, or causing to be presented, claims for payment or approval from Medicare, Medicaid, or other federal or state health care programs that are false or fraudulent; knowingly making or causing a false statement material to a false or fraudulent claim or an obligation to pay or transmit money or property to the federal government; or knowingly concealing or knowingly and improperly avoiding or decreasing such an obligation. 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. Manufacturers can be held liable under the federal False Claims Act even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. Pharmaceutical and other healthcare companies have been, and continue to be, prosecuted under these laws, among other things, for allegedly providing kickbacks to providers or patients or causing false claims to be submitted because of the companies’ marketing of the product for unapproved, off-label, and thus 38 generally non-reimbursable, uses. Similar to the AKS, a person or entity does not need to have actual knowledge of these statutes or specific intent to violate them in order to have committed a violation. • The Civil Monetary Penalties Law, which covers a variety of conduct, often violations under other laws, and includes penalties for violating the AKS, causing the submission of false claims, and offering or transfer of 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 healthcare program. • The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, imposes criminal and civil liability for knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program (e.g., public or private) or making any false, fictitious or fraudulent statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters. Like the AKS, the Patient Protection and Affordable Care Act, or the ACA, amended the intent standard for certain healthcare fraud statutes under HIPAA such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. • HIPAA, also imposes requirements related to the privacy, security and transmission of individually identifiable health information that may apply to many healthcare providers, physicians, and third-party payors with whom we interact. • The federal Physician Payments Sunshine Act and its implementing regulations, which require manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to CMS, under the Open Payments Program, information related to payments or other transfers of value made to physicians (which has the same meaning as under Section 1861(r) of the Social Security Act, which generally includes doctors of medicine, osteopathy, dentists, optometrists, podiatrists and chiropractors who are legally authorized to practice by a state), to certain non-physician providers such as physician assistants and nurse practitioners, and to teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members. • Federal government price reporting laws, which require manufacturers to calculate and report certain calculated product prices to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement under governmental healthcare programs. • Federal consumer protection and unfair competition laws broadly regulate marketplace activities and activities that potentially harm consumers. • Analogous state laws and regulations, such as state anti-kickback, false claims, consumer protection and unfair competition laws which may apply to pharmaceutical business practices, including but not limited to, research, distribution, sales and marketing arrangements as well as submitting claims involving healthcare items or services reimbursed by any third-party payor, including commercial insurers; state 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 that otherwise restricts payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to file reports with states regarding pricing and marketing information, such as the tracking and reporting of gifts, compensation and other remuneration and items of value provided to healthcare professionals and entities; state and local laws requiring the registration of pharmaceutical sales representatives; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts. The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform. In addition, commercialization of any drug product outside the U.S. will also likely be subject to foreign equivalents of the healthcare laws mentioned above, among other foreign laws. Because of the breadth of these laws and the narrowness of the statutory exceptions and safe harbors available, it is possible that some of our business activities could be subject to challenge under one or more of such laws in the future. If our operations are found to be in violation of any of such laws or any other governmental regulations that apply to us, we may be subject to, on a corporate or individual basis, penalties, including civil and criminal penalties, damages, fines, the curtailment or restructuring of our operations, the exclusion from participation in federal and state healthcare programs and even imprisonment, any of which could materially adversely affect our ability to operate our business and our financial results. In addition, the cost of implementing sufficient systems, controls, and processes to ensure compliance with all of the aforementioned laws could be significant. Any action for violation of these laws, even if successfully defended, could cause us to incur significant legal expenses and divert management’s attention from the operation of the company’s business. If any of the physicians or other healthcare providers or entities with whom we expect to do business is found noncompliant with applicable laws, that person or entity may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs. It is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent inappropriate conduct may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations. Efforts to ensure that our business arrangements will comply with applicable healthcare laws may involve substantial costs. It is 39 possible that governmental and enforcement authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law interpreting applicable fraud and abuse or other healthcare laws and regulations. If any such actions are instituted against us and we are not successful in defending ourselves or asserting our rights those actions, our business may be impaired. In the ordinary course of our business, we and the third parties upon which we rely collect, receive, store, or otherwise process personal data, including information we may collect about participants in our clinical trials. Our data processing activities subject us to numerous, evolving data privacy and cybersecurity obligations, such as various laws, regulations, guidance, industry standards, external and internal privacy and security policies, contractual requirements, and other obligations relating to data privacy and cybersecurity. The legislative and regulatory framework for the processing of personal data worldwide is rapidly evolving in a manner that is increasingly stringent and, globally, this legal and regulatory framework is likely to remain uncertain for the foreseeable future. In the U.S., numerous federal, state and local laws and regulations, including federal health information privacy laws, state information security and data breach notification laws, federal consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), state consumer protection and privacy laws, and other similar laws (e.g., wiretapping and communications interception laws) govern the processing of health-related and other personal data. At the state level, numerous U.S. states have enacted comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording individuals certain rights concerning their personal data. Similar laws are being considered in several other states, as well as at the federal and local levels, and we expect more states to pass similar laws in the future. While existing state comprehensive privacy laws exempt some data processed in the context of clinical trials, these developments may further complicate compliance efforts, and increase legal risk and compliance costs for us and the third parties upon whom we rely. Additionally, a smaller number of states have passed or are considering laws governing the privacy of consumer health data. For example, Washington’s My Health My Data Act broadly defines consumer health data, creates a private right of action to allow individuals to sue for violations of the law, imposes stringent consent requirements, and grants consumers certain rights with respect to their health data, including to request deletion of their information. Connecticut and Nevada have also passed similar laws regulating consumer health data. These various data privacy and cybersecurity laws may impact our business activities, including our identification of research subjects, relationships with business partners and ultimately the marketing and distribution of our products. Additionally, to the extent we collect personal information from individuals outside of the United States, through clinical trials or otherwise, we are, or may become, subject to foreign data privacy and security laws, such as the European Union’s General Data Protection Regulation 2016/679 (or EU GDPR) and other national data protection legislation in force in relevant EEA Member States, and the EU GDPR as it forms part UK law by virtue of section 3 of the European Union (Withdrawal) Act 2018 (or UK GDPR). Foreign data privacy and cybersecurity laws impose significant and complex compliance obligations on entities that are subject to those laws, as more fully discussed in the section titled “Risk Factors—Risks related to government regulation”. Current and Future U.S. Healthcare Reform Legislation Payors, whether domestic or foreign, or governmental or private, are developing increasingly sophisticated methods of controlling healthcare costs and those methods are not always specifically adapted for new and innovative technologies, such as pharmaceutical products like [ 225 Ac]Ac-AKY-1189. In both the U.S. and certain foreign jurisdictions, there have been a number of legislative and regulatory changes to the health care system that could impact our ability to sell products profitably. By way of example, the U.S. and state governments continue to propose and pass legislation designed to reduce the cost of healthcare. In March 2010, the ACA, was enacted, 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; created the Medicare Part D coverage gap discount program, in which manufacturers agree to provide 70% point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; 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 in additional downward pressure on the price for any approved products. Since its enactment, there have been, and continue to be, numerous judicial, administrative, executive, and legislative challenges to certain aspects of the ACA, and there could be additional amendments to the ACA in the future. It is unclear whether the ACA will be overturned, repealed, replaced, or further amended. We cannot predict what effect further changes to the ACA would have on our business. Additionally, there have been several U.S. congressional inquiries and proposed federal and proposed and enacted state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient support programs, reduce the costs of drugs under Medicare and reform government program reimbursement 40 methodologies for drug products. For example, on August 16, 2022, the Inflation Reduction Act of 2022, or IRA, was signed into law by President Biden. The IRA includes several provisions that may impact pharmaceutical companies to varying degrees, including provisions that create a $2,000 out-of-pocket cap for Medicare Part D beneficiaries; impose new manufacturer financial liability on all drugs in Medicare Part D; allow the U.S. government to negotiate Medicare Part B and Part D pricing caps for certain high-cost drugs and biologics without generic or biosimilar competition; require companies to pay rebates to Medicare for drug prices that increase faster than inflation; and delay the rebate rule that would require pass through of pharmacy benefit manager rebates to beneficiaries. Generally, these government prices can apply as soon as nine years (for small-molecule drugs) or 13 years (for biological products) from their FDA approval and will be capped at a statutory ceiling price that is likely to represent a significant discount from average prices to wholesalers and direct purchasers. The implementation of the IRA is currently subject to ongoing litigation that challenges the constitutionality of the IRA’s Medicare drug price negotiation program. The full impact of the IRA on our business and the pharmaceutical and healthcare industry in general is not yet known. At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Employees and Human Capital Resources As of December 31, 2025, we had 79 full-time employees. Of these employees, 67 are engaged in research and development and 12 are engaged in business development, finance, legal, and general management and administration. Our human capital resources objectives include identifying, recruiting, retaining, incentivizing and integrating our existing and new employees, advisors and consultants. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good. Corporate Information We were originally incorporated under the laws of the State of Delaware in August 2020 under the name HotKnot Therapeutics, Inc. We changed our name to Aktis Oncology, Inc. in April 2021. Our principal executive offices are located at 17 Drydock Avenue, Suite 17-401, Boston, Massachusetts 02210 and our telephone number is (617) 461-4023. Available Information We file electronically with the Securities and Exchange Commission, the SEC, our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, proxy statements and other information. Our SEC filings are available to the public over the Internet at the SEC’s website at http://www.sec.gov. Our website address is https://www.aktisoncology.com. We make available on our website, under “Investors,” free of charge, copies of these reports as soon as reasonably practicable after filing or furnishing these reports with the SEC. The information contained in, or accessible through, our website does not constitute a part of this Annual Report. All statements made in any of our securities filings, including all forward-looking statements or information, are made as of the date of the document in which the statement is included, and we do not assume or undertake any obligation to update any of those statements or documents unless we are required to do so by law. 41 Ite m 1A. Risk Factors. You should carefully consider the risks and uncertainties described below, as well as the other information in this Annual Report, including our consolidated financial statements and the related notes appearing elsewhere in this Annual Report and the sections of this Annual Report titled “Special Note Regarding Forward-Looking Statements” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” before you make an investment decision in our common stock. The risks described below are not the only risks that we face. The occurrence of any of the following risks, or of 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, results of operations and prospects. Risks related to our limited operating history, financial condition and need for additional capital We have incurred significant losses since our inception, have no products approved for sale, and we expect to incur losses for the foreseeable future. Development of radiopharmaceutical product candidates is a highly speculative undertaking and involves a substantial degree of risk. We are still in the early stages of development of our product candidates and our lead product candidate, [ 225 Ac]Ac-AKY-1189, is being evaluated in a Phase 1b clinical trial for locally advanced or metastatic urothelial cancer, or UC, and other Nectin-4 expressing tumors. We have no products licensed for commercial sale and have not generated any revenues from product sales to date, and we continue to incur significant research and development and other expenses related to our ongoing operations. As such, we have incurred significant losses since inception, and have financed our operations principally through equity financings. We expect that it will be several years, if ever, before we have a commercialized product candidate and generate revenue from sales. Our net losses for the years ended December 31, 2025 and 2024 were $63.7 million and $44.0 million, respectively. As of December 31, 2025, we had an accumulated deficit of $156.6 million. We anticipate that our expenses and operating losses will increase substantially as we: • advance our lead product candidate, [ 225 Ac]Ac-AKY-1189 for Nectin-4 expressing tumors, through clinical trials; • advance our second product candidate, [ 225 Ac]Ac-AKY-2519 for B7-H3 expressing tumors, into clinical trials; • continue to advance our miniprotein radioconjugate platform; • acquire or in-license other product candidates, targeting molecules and technologies; • pursue investigational new drug, or IND,-enabling preclinical studies for our other programs; • conduct preclinical studies and clinical studies for our other product candidates; • seek to identify additional product candidates; • continue to expand partnerships with domestic and international isotope suppliers to create redundancies in our supply chain; • scale up our supply of 225 Ac and other radioisotopes; • seek regulatory approval of product candidates that successfully complete clinical development; • obtain, expand, maintain, defend, protect and enforce our intellectual property portfolio; • continue to expand manufacturing capabilities through additional in-house facilities and expertise, as well as additional third party contractors to enable global commercial scale; • continue to utilize third parties to manufacture our lead product candidate; • undertake pre-commercial activities to enhance commercialization prospects for any current or future product candidates that we may seek to obtain regulatory approval for; • ultimately establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain marketing approval; • expand our operational, financial, and management systems and increase personnel, including personnel to support our preclinical and clinical development, manufacturing and commercialization efforts; and • add operational, legal, compliance, financial and management information systems and personnel to support our research, product development and future commercialization efforts, as well as to support our operations as a public company. 42 Because of the numerous risks and uncertainties associated with the development of radiopharmaceutical therapies, we are unable to accurately predict the timing or amount of increased expenses. The size of our future net losses will depend, in part, on the rate of future growth of our expenses and our ability to generate revenue. Our prior losses and expected future losses have had and will continue to have an adverse effect on our stockholders’ equity and working capital. Even if we succeed in commercializing one or more of our product candidates, we will continue to incur substantial research and development and other expenditures to develop, seek regulatory approval for, and market additional product candidates. We may encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect our business. For example, if we are required by the United States Food and Drug Administration, or FDA, or comparable foreign regulatory authorities to perform studies or clinical trials in addition to those we currently anticipate, or if there are any delays in commencing or completing our clinical trials or the development of any product candidates, our expenses could increase and commercial revenue could be further delayed and more uncertain, which will adversely affect our business. We may not be successful in navigating these challenges, which may adversely affect our business, results of operations and prospects. Our limited operating history may make it difficult for you to evaluate our prospects and likelihood of success. We have a limited operating history upon which you can evaluate our business and prospects. Since our inception in August 2020, we have devoted substantially all our resources and efforts to organizing and staffing our company, business planning, raising capital, conducting discovery and research activities, filing patent applications, identifying potential product candidates, undertaking preclinical studies, in-licensing technology, building out our manufacturing facility and establishing arrangements with third parties for the supply and manufacture of our product candidates and component materials. We have commenced a multi-site Phase 1b clinical trial in the United States to evaluate our lead product candidate, [ 225 Ac]Ac-AKY-1189, for the treatment of locally advanced or metastatic UC and other Nectin-4 expressing tumors. We have not yet demonstrated our ability to successfully complete any clinical trials, obtain regulatory approvals, manufacture a commercial scale product supply, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful commercialization. Additionally, we expect our financial condition and operating results to continue to fluctuate significantly from period to period due to a variety of factors, many of which are beyond our control. Such factors include, among other things, the timing of, cost of, and level of investment in, research, development, and commercialization activities, which could vary over time. Consequently, any predictions you may make about our future success or viability may not be as accurate as they could be if we had a longer operating history. In addition, as a young business, we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors. We will need to transition at some point from a company with a research and development focus to a company capable of supporting commercial activities. We may not be successful in such a transition. We will require additional funding to finance operations. If we are unable to raise capital when needed, or on acceptable terms, we would be forced to delay, reduce, or eliminate our research and product candidate development programs. Developing radiopharmaceutical product candidates, including conducting preclinical studies and clinical trials, is a very time-consuming, capital-expensive, and uncertain process that takes years to complete. We have commenced a multi-site Phase 1b clinical trial in the United States to evaluate our lead program, [ 225 Ac]Ac-AKY-1189, for the treatment of locally advanced or metastatic UC and other Nectin-4 expressing tumors and are preparing to commence a Phase 1b clinical trial for [ 225 Ac]Ac-AKY-2519. We are also evaluating multiple current product candidates in preclinical studies. We expect our expenses to increase substantially in connection with our ongoing activities, particularly as we continue the research and development of, advance the preclinical and clinical activities of, and seek regulatory approval for, [ 225 Ac]Ac-AKY-1189 for Nectin-4 expressing tumors from the FDA and other foreign regulatory authorities, as well as our other product candidates. In addition, if we obtain regulatory approval for [ 225 Ac]Ac-AKY-1189 for any Nectin-4 expressing tumor or our other product candidates, we expect to incur significant commercialization expenses related to sales, marketing, manufacturing and distribution to the extent that such sales, marketing, manufacturing and distribution are not the responsibility of our collaborators. We may also need to raise additional funds sooner if our preclinical and clinical activities take longer than expected, as a result of regulatory approvals or otherwise, or if we choose to pursue additional indications and geographies for any of our product candidates or otherwise expand more rapidly than we presently anticipate. Furthermore, we expect to incur additional costs associated with operating as a public company. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on attractive terms, we will be forced to delay, reduce, or eliminate programs, and may be unable to expand our operations or otherwise capitalize on our business opportunities, as desired, which could materially affect our business, financial condition, results of operations and prospects. As of December 31, 2025, we had $226.8 million in cash, cash equivalents and marketable securities. Based on our current business plans, we believe that our existing cash, cash equivalents and marketable securities, together with the net proceeds of approximately $335.3 million from our initial public offering completed in January 2026, will be sufficient to fund our operating expenses and capital expenditure requirements into 2029. We have based this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently expect, requiring us to seek additional funds sooner than planned, through public or private equity or debt financings or other sources, such as strategic collaborations. Our failure to raise capital or enter into such other arrangements when needed would have a negative impact on our financial condition and could force us to 43 delay, limit, reduce or terminate clinical trials, our research and development programs or other operations, or lead us to grant rights to third parties to develop and market product candidates that we would otherwise prefer to develop and market ourselves. In addition, we may seek additional capital opportunistically due to favorable market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans. Attempting to secure additional financing may divert our management from our day-to-day activities. See “Management’s discussion and analysis of financial condition and results of operations—Liquidity and capital resources.” Our future capital requirements will depend on, and could increase significantly because of many factors including: • the scope, progress, results and costs related to the clinical development of [ 225 Ac]Ac-AKY-1189 for Nectin-4 expressing tumors; • the scope, progress, results and costs of planned clinical trials for [ 225 Ac]Ac-AKY-2519 for B7-H3 expressing tumors and our other future product candidates; • the costs, timing and outcome of regulatory review of our product candidates; • the cost of advancing and furthering our miniprotein radioconjugate platform; • the costs of establishing, operating and maintaining our manufacturing facility, or securing other manufacturing arrangements for clinical-supply and commercial production; • the cost and availability of sufficient supply of 225 Ac and other radioisotopes; • the achievement of milestones or occurrence of other developments that trigger payments by us or our collaborators under any current or future collaboration agreements; • our ability to establish and maintain additional collaborations on favorable terms, if at all; • the emergence of competing therapies for oncology indications and other adverse market developments; • the costs of preparing, filing and prosecuting patent applications, obtaining, maintaining, protecting, defending and enforcing our intellectual property rights and defending intellectual property-related claims; • the extent to which we acquire or in-license other product candidates and technologies; and • the costs of establishing or contracting for sales and marketing capabilities if we obtain regulatory clearances to market [ 225 Ac]Ac-AKY-1189 for any Nectin-4 expressing tumors or any other current or future product candidates. We cannot be certain that additional funding will be available on acceptable terms, or at all. If we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we may have to significantly delay, scale back or discontinue the development or commercialization of our product candidates or other research and development initiatives. Any of our current or future license agreements may also be terminated if we are unable to meet the payment or other obligations under the agreements. We have not generated any revenue to date and may never be profitable. Our ability to become profitable depends upon our ability to generate revenue. To date, we have not generated any revenue. We do not expect to generate significant product revenue unless or until we successfully complete clinical development and obtain regulatory approval of, and then successfully commercialize, at least one of our product candidates. Other than [ 225 Ac]Ac-AKY-1189, which is in a Phase 1b clinical trial for the treatment of locally advanced or metastatic UC and other Nectin-4 expressing tumors, all of our product candidates are in the preclinical stages of development and will require additional preclinical studies and clinical development as well as regulatory review and approval, substantial investment, access to sufficient commercial manufacturing capacity and significant marketing efforts before we can generate any revenue from product sales. We will face significant development risk as our product candidates, including [ 225 Ac]Ac-AKY-1189, advance through clinical development. Our ability to generate revenue depends on a number of factors, including, but not limited to: • timely completion of our preclinical studies and our current and future clinical trials, which may be significantly slower or more costly than we currently anticipate and will depend substantially upon the performance of third-party contractors; • our ability to complete IND-enabling studies and successfully submit IND applications or comparable applications to allow us to initiate clinical trials for any other current or future product candidates; • whether we are required by the FDA or similar foreign regulatory authorities to conduct additional clinical trials or other studies beyond those planned to support the approval and commercialization of our product candidates or any future product candidates; • our ability to demonstrate to the satisfaction of the FDA or similar foreign regulatory authorities the safety, potency, purity and acceptable risk-to-benefit profile of our product candidates or any future product candidates; • the prevalence, duration and severity of potential side effects or other safety issues experienced with our product candidates or future product candidates, if any; 44 • the timely receipt of necessary marketing approvals from the FDA or similar foreign regulatory authorities; • the willingness of physicians, operators of clinics and patients to utilize or adopt any of our product candidates or future product candidates as potential cancer treatments; • our ability and the ability of third parties with whom we contract to manufacture adequate clinical and commercial supplies of our product candidates or any future product candidates, remain in good standing with regulatory authorities and develop, validate and maintain commercially viable manufacturing processes that are compliant with current good manufacturing practices, or cGMP; • our ability to successfully develop a commercial strategy and thereafter commercialize our product candidates or any future product candidates in the United States and internationally, if licensed for marketing, reimbursement, sale and distribution in such countries and territories, whether alone or in collaboration with others; and • our ability to establish, maintain, enforce, protect and defend intellectual property rights in and to our product candidates or any future product candidates. Many of the factors listed above are beyond our control, and could cause us to experience significant delays or prevent us from obtaining regulatory approvals or commercialize our product candidates. Even if we are able to commercialize our product candidates, we may not achieve or maintain profitability. If we are unable to generate sufficient revenue through the sale of our product candidates or any future product candidates, we may be unable to continue operations without continued funding. Raising additional capital may cause dilution to our stockholders restrict our operations or require us to relinquish rights to our technologies or product candidates. We expect our expenses to increase in connection with our planned operations. Unless and until we can generate a substantial amount of revenue from our product candidates, we expect to finance our future cash needs through public or private equity offerings, debt financings, collaborations, licensing arrangements or other sources, or any combination of the foregoing. In addition, we may seek additional capital due to favorable market conditions or strategic considerations, even if we believe that we have sufficient funds for our current or future operating plans. Disruptions in the financial markets in general may make equity and debt financing more difficult to obtain and may have a material adverse effect on our ability to meet our fundraising needs. To the extent that we raise additional capital through the sale of common stock, convertible securities or other equity securities, your ownership interest may be diluted, and the terms of these securities could include liquidation or other preferences and anti-dilution protections that could adversely affect your rights as a common stockholder. In addition, debt financing, if available, may result in fixed payment obligations and may involve agreements that include restrictive covenants that limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, creating liens, redeeming shares or declaring dividends, that could adversely impact our ability to conduct our business. In addition, securing financing could require a substantial amount of time and attention from our management and may divert a disproportionate amount of their attention away from day-to-day activities, which may adversely affect our management’s ability to oversee the development of our product candidates. If we raise additional funds through collaborations, strategic alliances, distribution or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds when needed, we would be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves. Any additional fundraising efforts we undertake may divert our management from their day-to-day activities, which may adversely affect our ability to develop and commercialize our product candidates. Risks related to our business and development of our product candidates We are early in our development efforts. If we are unable to develop, and commercialize, any of our current or future product candidates through clinical development, obtain regulatory approval and ultimately commercialize our product candidates, or if we experience significant delays in doing so, our business will be materially harmed. We are early in our development efforts. The success of our business depends upon our ability to identify, develop, and commercialize targeted radiopharmaceuticals across a range of oncology indications. [ 225 Ac]Ac-AKY-1189, our most advanced product candidate, is in a Phase 1b clinical trial for the treatment of locally advanced or metastatic UC and other Nectin-4 expressing tumors. Commencing clinical trials for our current or future product candidates in the United States is subject to clearance by the FDA of an IND application and finalizing the trial design based on discussions with the FDA. In the event that the FDA requires us to complete additional preclinical studies or we are required to satisfy other FDA requests prior to commencing clinical trials, the start of our planned future clinical trials may be delayed or we may be unsuccessful obtaining clearance to proceed into clinical development. In addition, clinical trials conducted in one country, may not be accepted by regulatory authorities in other countries, and regulatory approval in one country does not guarantee regulatory approval in any other country. Although the FDA may accept data from clinical trials conducted outside the United States, acceptance of these data is subject to conditions imposed by the FDA, and there can be no assurance that the FDA will accept data from trials conducted outside of the United States. If the FDA does not 45 accept the data from any trial that we conduct outside the United States, it would likely result in the need for additional trials, which would be costly and time-consuming and could delay or permanently halt our development of the applicable product candidates. Our ability to generate product revenues, which we do not expect will occur for many years, if ever, will depend heavily on the successful development and eventual commercialization of one or more of our product candidates. The success of our product candidates will depend on several factors, including the following: • successful completion of clinical trials; • effective INDs or comparable foreign applications that allow commencement of our planned clinical trials or future clinical trials for any product candidates we may develop; • successful completion of planned preclinical studies and initiation of clinical trials for our other product candidates; • successful patient enrollment in, and completion of, clinical trials; • the ability to successfully develop [ 225 Ac]Ac-AKY-1189 for any Nectin-4 expressing tumors and [ 225 Ac]Ac-AKY-2519 for any B7-H3 expressing tumors; • the ability to successfully develop additional product candidates; • our ability to demonstrate to the satisfaction of the FDA or any comparable foreign regulatory authority that the applicable product candidate’s risk-benefit ratio for its proposed indication is acceptable; • timely receipt of approvals for product candidates from applicable regulatory authorities; • the extent of any required post-regulatory approval commitments to applicable regulatory authorities; • obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our product candidates; • sourcing clinical and, if approved for commercial sale, commercial supplies for the radioisotopes used to manufacture our product candidates; • securing reliable transport for our product candidates given that isotope stability times are limited once a molecule has been bound; • successfully establishing and operating our manufacturing facility; • the ability of dosimetry and imaging assessments to demonstrate sufficient tumor uptake of imaging radioisotopes conjugated to our miniproteins; • making and maintaining arrangements with third-party manufacturers for both clinical and commercial supplies of our product candidates; • establishing sales, marketing and distribution capabilities and successfully launching commercial sales of our products, if and when approved, whether alone or in collaboration with others; • acceptance of our products, if and when approved, by patients, the medical community and third-party payors; • effectively competing with other cancer therapies; • educating medical personnel regarding the potential side effect profile of our product candidates; • facilitating patient access to the facilities able to administer our product candidates, if approved; • obtaining and maintaining third-party coverage and adequate reimbursement; and • maintaining a continued acceptable safety profile of our products following regulatory approval. If we do not achieve one or more of these factors in a timely manner, or at all, we could experience significant delays or be unable to successfully commercialize our product candidates, which would materially harm our business. Our business is highly dependent on our lead product candidate, [ 225 Ac]Ac-AKY-1189, for the treatment of Nectin-4 expressing tumors. We must complete clinical trials before we can seek regulatory approval and begin commercialization of [ 225 Ac]Ac-AKY-1189. If we are unable to obtain regulatory approval for, and successfully commercialize, [ 225 Ac]Ac-AKY-1189, our business may be materially harmed, and such failure may affect our other current or future product candidates. The process for obtaining marketing approval for any product candidate, including [ 225 Ac]Ac-AKY-1189, is very long and risky and there will be significant challenges for us to address to obtain marketing approval as planned, if at all. There is no guarantee that the results obtained in our ongoing and planned clinical trials of [ 225 Ac]Ac-AKY-1189 will be sufficient to obtain regulatory approval. Furthermore, success in an early-stage trial does not necessarily mean a later stage trial will be successful. In addition, because our other product candidates are based on similar technology of our lead product candidate, if [ 225 Ac]Ac-AKY-1189 46 encounters safety or efficacy problems, manufacturing or supply interruptions, developmental delays, regulatory issues, or other problems, our development plans and business related to other product candidates could be significantly harmed. Preclinical and clinical development is a lengthy and expensive process with uncertain timelines and uncertain outcomes. If preclinical studies or clinical trials of a product candidate are prolonged or delayed, we may be unable to obtain required regulatory approvals, and therefore be unable to commercialize [ 225 Ac]Ac-AKY-1189, [ 225 Ac]Ac-AKY-2519 or any of our future product candidates on a timely basis or at all. We, and any future collaborators, are not permitted to commercialize, market, promote or sell any product candidate in the United States without obtaining regulatory approval from the FDA. Foreign regulatory authorities, such as the European Medicines Agency, or EMA, impose similar requirements. The time required to obtain approval by the FDA and comparable foreign authorities is unpredictable, but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including substantial discretion of the regulatory authorities. In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions. We, and any future collaborators, must complete additional preclinical studies and clinical trials to demonstrate the safety and efficacy of our product candidates in humans before we will be able to obtain these approvals. For our current and future product candidates, we may not be able to file IND applications, or similar applications outside the United States, on the timelines we expect. For example, we may experience supply or manufacturing delays or other delays with IND-enabling, or equivalent foreign preclinical studies. Moreover, we cannot be sure that submission of an IND application, or similar applications outside the United States, will result in the FDA, or comparable foreign regulatory authorities, allowing clinical trials to begin, or that, once begun, issues will not arise that suspend or terminate clinical trials. Additionally, even if such regulatory authorities agree with the design and implementation of the clinical trials set forth in an IND application, or similar applications outside the United States, we cannot guarantee that such regulatory authorities will not change their requirements in the future. We also cannot predict that approval of an IND application or similar application by the FDA or comparable foreign regulatory authority will result in approval of similar applications to conduct clinical trials. These considerations also apply to new clinical trials we may submit as amendments to existing INDs or similar approvals outside the United States. We do not know whether planned clinical trials will begin on time, need to be redesigned, enroll patients on time, or be completed on schedule, if at all. Clinical trials can be delayed, suspended, or terminated for a variety of reasons, including the following: • delays in or failure to obtain regulatory authorization to commence a clinical trial; • delays in or failure to obtain institutional review board, or IRB, approval at each site or national competent authority approvals including positive ethics committee opinions; • delays in or failure to reach agreement on acceptable terms with prospective contract research organizations, or CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; • difficulty in recruiting clinical trial investigators of appropriate competencies and experience; • delays in establishing the appropriate dosage levels in clinical trials; • delays in or failure to recruit and enroll suitable patients to participate in a clinical trial, as well as inclusion and exclusion criteria and patients’ prior lines of therapy and treatment; • lower than anticipated retention rates of patients in clinical trials; • failure to have patients complete a trial or return for post-treatment follow-up; • clinical sites deviating from trial protocol or dropping out of a clinical trial; • delays adding new investigators or clinical trial sites; • our third-party research contractors failing to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; • changes in regulatory requirements, policies, and guidelines; • our ability to obtain sufficient radioactive supplies, and to manufacture and deliver sufficient quantities of a product candidate for use in clinical trials; • the quality or stability of a product candidate falling below acceptable standards; • changes in the treatment landscape for our target indications in oncology that may make any of our current or future product candidates no longer relevant; • third-party actions claiming infringement by our product candidates in clinical trials outside the United States and obtaining injunctions interfering with our progress; and 47 • business interruptions resulting from geo-political actions, including war and terrorism, natural disasters including earthquakes, typhoons, floods, and wildfires, or disease. Moreover, clinical trials must be conducted in accordance with the FDA and comparable foreign regulatory authorities’ legal requirements, regulations, and guidelines, and are subject to oversight by regulatory authorities and IRBs or ethics committees at the medical institutions where the clinical trials are conducted. Safety or tolerability concerns could cause us or regulatory authorities, as applicable, to suspend or terminate a clinical trial if it is found that the participants are being exposed to unacceptable health risks, undesirable side effects, or other unfavorable characteristics of the product candidate, or if such undesirable effects or risks are found to be caused by a chemically or mechanistically similar therapeutic or therapeutic candidate. We could encounter delays if a clinical trial is suspended or terminated by us, by the IRBs or ethics committees of the institutions in which such trials are being conducted, by the data review committee or data safety monitoring board for such trial or by the FDA, or comparable foreign regulatory authorities. Such authorities may impose such a suspension or termination due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or comparable foreign regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a product, changes in governmental regulations or administrative actions, or lack of adequate funding to continue the clinical trial. In 2021, the FDA launched Project Optimus as an initiative to reform the dose optimization and dose selection paradigm in oncology drug development with the goal of advancing an oncology dose-finding and dose optimization paradigm that emphasizes dose selections that maximize efficacy as well as safety and tolerability. In support of this initiative, the FDA may request sponsors of oncology product candidates to conduct dose optimization studies before permitting sponsors to initiate a pivotal study. In early 2023, the FDA issued a draft guidance intended to assist sponsors in identifying the optimal dosages for these products during clinical development and prior to applying for approval for a new indication and usage as well as another draft guidance intended to provide recommendations to sponsors of anticancer drugs or biological products on considerations for designing trials intended to support accelerated approval. In August 2004, the FDA issued final guidance on optimizing the dosage of oncology drugs and biologics, which noted that while the guidance did not contain specific recommendations for radiopharmaceuticals, some of the recommendations in the guidance may be applicable to these products. If we are required to conduct dose optimizing studies, such studies may delay our product development activities. If we or our collaborators are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies governing clinical trials, our development plans may be impacted. For example, in December 2022, with the passage of Food and Drug Omnibus Reform Act, or FDORA, Congress required sponsors to develop and submit a diversity action plan for each Phase 3 clinical trial or any other “pivotal study” of a new drug or biological product. These plans are meant to encourage the enrollment of more diverse patient populations in late-stage clinical trials of FDA-regulated products. In June 2024, as mandated by FDORA, the FDA issued draft guidance outlining the general requirements for Diversity Action Plans, or DAPs. Unlike most guidance documents issued by the FDA, the DAP guidance when finalized will have the force of law because FDORA specifically dictates that the form and manner for submission of DAPs are specified in FDA guidance. On January 27, 2025, in response to an Executive Order issued on January 21, 2025, on Diversity, Equity and Inclusion programs, the FDA removed this draft guidance from its website. This action raises questions about the applicability of statutory obligations to submit DAPs and the agency’s current thinking on best practices for clinical development. Furthermore, even if we are able to complete our manufacturing facility, we will continue to rely on contract manufacturing organizations, or CMOs, and contract development and manufacturing organization, or CDMOs, for the proper and timely manufacturing of our product candidates in accordance with cGMP requirements. We also intend to continue to rely on CROs and clinical trial sites to ensure the proper and timely conduct of our clinical trials in compliance with good clinical practice, or GCP, requirements. While we have agreements governing their committed activities, we will have limited influence over their actual performance. To the extent our CMOs fail to comply with cGMP or to perform their manufacturing obligations in a timely manner, or our CROs fail to enroll participants for our clinical trials, fail to conduct the study in accordance with GCP, or are delayed for a significant time in the execution of trials, including achieving full enrollment, we may be affected by increased costs, program delays, or both, which may harm our business. Moreover, any clinical trials that we may conduct in countries outside the United States may subject us to further delays and expenses because of increased shipment and distribution costs, additional regulatory requirements, and the engagement of non-U.S. CROs, as well as expose us to risks associated with clinical investigators who are unknown to the FDA, and different standards of diagnosis, screening, and medical care. The FDA may decline to accept the data we obtain from these clinical studies in support of an IND application or a biologics license application, or BLA, in the United States, which may require us to repeat or conduct additional preclinical studies or clinical trials that we did not anticipate in the United States, and therefore we may be unable to commercialize our current or future product candidates, on a timely basis or at all in the United States. Foreign regulatory authorities may also decline to accept data obtained from clinical studies conducted in the United States in support of a related marketing authorization application which may lead to similar risks in countries outside the United States. If we experience delays in the completion of, or termination of, any clinical trial, the commercial prospects of [ 225 Ac]Ac-AKY-1189 for Nectin-4 expressing tumors, or our other product candidates will be harmed, and our ability to generate revenue from sales 48 of any products will be delayed. In addition, any delays in completing our clinical trials will increase our costs, slow down our development and approval process, and jeopardize our ability to commence sales and generate revenue. Significant clinical trial delays could also allow our competitors to bring products to market before we do or shorten any periods during which we have the exclusive right to commercialize our product candidates and impair our ability to commercialize our product candidates and may harm our business, financial condition, results of operations and prospects. Our clinical trials may fail to demonstrate substantial evidence of the safety and efficacy of [ 225 Ac]Ac-AKY-1189, [ 225 Ac]Ac-AKY-2519, or any of our future product candidates, which would prevent or delay or limit the scope of regulatory approval and commercialization. To obtain the requisite regulatory approvals to market and sell [ 225 Ac]Ac-AKY-1189, [ 225 Ac]Ac-AKY-2519, or any of our future product candidates, we must demonstrate through clinical trials that such product candidates are safe and effective for use in each targeted indication. Most product candidates that begin clinical trials are never approved by regulatory authorities for commercialization. Unforeseen side effects could arise either during clinical development or, if such side effects are more rare, after our products have been approved by regulatory authorities and the approved product has been marketed, resulting in the exposure of additional patients than if such side effect had arisen during a clinical trial. Furthermore, the results of our Phase 1b clinical trial may not demonstrate the clinical utility of [ 225 Ac]Ac-AKY-1189, or reveal an unacceptable safety profile. Additionally, assessments of the long-term safety of targeted alpha-emitting isotope therapies in humans have been limited, and there may be long-term effects from treatment with [ 225 Ac]Ac-AKY-1189 or any of our other current or future product candidates that we cannot predict at this time. Further, we may be unable to establish clinical endpoints that applicable regulatory authorities would consider clinically meaningful, and a clinical trial can fail at any stage of testing. Clinical trials that we conduct may not demonstrate the efficacy and safety necessary to obtain regulatory approval to market [ 225 Ac]Ac-AKY-1189, [ 225 Ac]Ac-AKY-2519 or any of our future product candidates. In some instances, there can be significant variability in safety or efficacy results between different 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. Additionally, our Phase 1b clinical trial for [ 225 Ac]Ac-AKY-1189 is, and we expect future trials of our product candidates to be, open-label trials, meaning both the patient and investigator know whether the patient is receiving the investigational product candidate. 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. Therefore, it is possible that positive results observed in an open-label trial would not be replicated in a controlled trial. Moreover, if unacceptable toxicities, undesirable side effects or adverse product-product interactions arise in the development of our product candidates alone or in combination with other therapies, we could suspend or terminate or trials, or the FDA or comparable foreign regulatory authorities could order us to cease clinical trials, deny approval of the product candidate for any or all targeted indications or require a more restrictive label. If the results of our clinical trials are inconclusive with respect to the efficacy of product candidates, if we do not meet the clinical endpoints with statistical and clinically meaningful significance, if there are safety concerns associated with our product candidates, or if the results observed cannot be replicated, we may be delayed in obtaining regulatory approval, if at all. Additionally, any safety concerns observed in our clinical trials, or in the clinical experience of others using our product candidates in “compassionate use” scenarios outside of the United States, or investigating similar products or modalities could impact our prospects for regulatory approval in those and other indications. Even if the trials are successfully completed, clinical data is often susceptible to varying interpretations and analyses, and we cannot guarantee that the FDA or comparable foreign regulatory authorities will interpret the results as we do, and more trials could be required before we submit any future BLA or comparable foreign application. We cannot guarantee that the FDA or comparable foreign regulatory authorities will view our product candidates as having efficacy even if positive results are observed in clinical trials. Moreover, results acceptable to support approval in one jurisdiction may be deemed inadequate by another regulatory authority to support regulatory approval in that other jurisdiction. To the extent that the results of the clinical trials are not satisfactory to the FDA or comparable foreign regulatory authorities for support of a regulatory application, approval of our product candidates may be significantly delayed, or we may be required to expend significant additional resources, which may not be available to us, to conduct additional development work. Even if regulatory approval is secured for a product candidate, the terms of such approval may limit the scope and use of the specific product candidate, which may also limit its commercial potential. Our approach to the discovery and development of product candidates using our miniprotein radioconjugate platform represents a novel approach to radiation therapy, which may create significant and potentially unpredictable challenges for us. Our future success depends on leveraging our miniprotein radioconjugate platform to successfully develop product candidates which are designed to treat advanced solid tumors, utilizing a novel approach to directed-radiation therapy. There are currently few approved radiopharmaceutical therapeutic products. In addition, there has been limited historical clinical trial experience, generally, for the development of radiopharmaceutical therapeutics. As a result, the design and conduct of clinical trials for these product candidates is uncertain and subject to increased risk. 49 While external beam radiation as a therapy for cancers has existed for decades, oncology treatment using systemic delivery of targeted radiopharmaceuticals in general, and alpha emitting isotopes specifically, is relatively new. Only one alpha emitting isotope therapy, Xofigo, which uses the isotope radium-223, or 223 radium, has been approved in the United States or the European Union, or EU, and only a limited number of clinical trials of products based on alpha emitting isotope therapies have commenced. Approved therapies containing beta emitting isotopes have also been limited. As such, it is difficult to accurately predict the developmental challenges we may incur for our product candidates as they proceed through discovery or identification, preclinical studies, and clinical trials. In addition, beyond the limited universe of patients treated with Xofigo, assessments of the long-term safety of targeted alpha emitting isotope therapies in humans have been limited, and there may be long-term effects from treatment with our product candidates that we cannot predict at this time. It is difficult for us to predict the time and cost of the development of our product candidates, and we cannot predict whether the application of our technology, or any similar or competitive technologies, will result in the identification, development, and regulatory approval of any products. There can be no assurance that any development problems we experience in the future related to our technology or any of our research programs will not cause significant delays or unanticipated costs, or that such development problems can be solved at all. Any of these factors may prevent us from completing our preclinical studies and clinical trials that we may initiate or commercializing any product candidates we may develop on a timely or profitable basis, if at all. Our product candidates may cause adverse events, undesirable side effects or have other properties that could halt their preclinical or clinical development, prevent, delay, or cause the withdrawal of their regulatory approval, limit their commercial potential, or result in significant negative consequences, including death of patients. If any of our product candidates receive marketing approval and we, or others, later discover that the product is less effective than previously believed or causes undesirable side effects that were not previously identified, our ability, or that of any potential future collaborators, to market the product could be compromised. As with most biological products, use of our product candidates could be associated with undesirable side effects or adverse events which can vary in severity from minor reactions to death and in frequency from infrequent to prevalent. Undesirable side effects or unacceptable toxicities caused by our product candidates could cause us or regulatory authorities to interrupt, delay, or halt clinical trials. Treatment-related undesirable side effects or adverse events could also affect patient recruitment or the ability of enrolled subjects to complete the trial, or could result in potential product liability claims. In addition, these side effects may not be appropriately or timely recognized or managed by the treating medical staff, particularly outside of the research institutions that collaborate with us. We have, and will need to continue to, educate and train medical personnel using our product candidates to understand their side effect profiles, for our ongoing Phase 1b clinical trial of [ 225 Ac]Ac-AKY-1189 and any future clinical trials, and upon any commercialization of any product candidates. Inadequate training in recognizing or managing the potential side effects of our product candidates could result in adverse events to patients, including death. Any of these occurrences may materially and adversely harm our business, financial condition, results of operations and prospects. Clinical trials of our product candidates must be conducted in carefully defined subsets of patients who have agreed to enter into clinical trials. Consequently, it is possible that our clinical trials, or those of any potential future collaborator, may indicate an apparent positive effect of a product candidate that is greater than the actual positive effect, if any, or alternatively fail to identify undesirable side effects. If one or more of our product candidates receives marketing approval and we, or others, discover that it is less effective than previously believed or causes undesirable side effects that were not previously identified, including during any long-term follow-up observation period recommended or required for patients who receive treatment using our products, a number of potentially significant negative consequences could result, including: • regulatory authorities may withdraw approvals of such product, seize the product, or seek an injunction against its manufacture or distribution; • we, or any future collaborators, may be required to recall the product, change the way such product is administered to patients or conduct additional clinical trials; • additional restrictions may be imposed on the marketing of, or the manufacturing processes for, the particular product; • regulatory authorities may require additional warnings on the label, such as a “black box” warning or a contraindication, or impose distribution or use restrictions; • we, or any future collaborators, may be required to create a Risk Evaluation and Mitigation Strategy, or REMS, which could include a medication guide outlining the risks of such side effects for distribution to patients, a communication plan for healthcare providers, and/or other elements to assure safe use; • we, or any future collaborators, may be subject to fines, injunctions or the imposition of civil or criminal penalties; • we, or any future collaborators, could be sued and held liable for harm caused to patients; • the product may become less competitive; and • our reputation may suffer. 50 Any of the foregoing could prevent us from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantly harm our business, results of operations, and prospects, and could adversely impact our financial condition, results of operations or the market price of our common shares. Results of preclinical studies, dosimetry assessments, and early-stage clinical trials may not be predictive of the results of future preclinical studies or clinical trials. Success in preclinical studies does not ensure that later preclinical studies or clinical trials will be successful. Several companies in the biotechnology industry have suffered significant setbacks in clinical trials, even after positive results in preclinical and earlier clinical trials. These setbacks have been caused by, among other things, negative preclinical findings identified after clinical trials have already commenced and safety or efficacy observations made in clinical trials, including previously unanticipated adverse events. We cannot predict if the FDA or comparable foreign regulatory authority will consider the data from our future preclinical studies sufficient to support approval of an IND application or similar application. In addition, preclinical data is often susceptible to varying interpretations and analyses, which could require us to repeat or conduct additional preclinical studies. Notwithstanding any potential promising results in earlier studies, we cannot be certain that we will not face similar setbacks. In addition, the results of our preclinical animal studies, may not be predictive of the results of outcomes in subsequent clinical trials on human subjects. Product candidates in clinical trials may fail to show the desired pharmacological properties or safety and efficacy traits despite having progressed through preclinical studies. The dosimetry assessments conducted using radioconjugates of our product candidates used may not be predictive of the anticancer effect or safety profile of our product candidates and we have had limited control and input over the conduct of this assessment and the reported results. The ability of our miniproteins to localize on tumors does not ensure that our product candidates will be successful at eradicating the tumor with an acceptable risk and safety profile, if at all. Likewise, the results of any early-stage clinical trials may not be predictive of the results of the later-stage clinical trials, which tend to enroll substantially larger numbers of patients. The preliminary results of clinical trials with smaller sample sizes can be disproportionately influenced by various biases associated with the conduct of small clinical trials, such as the potential failure of the smaller sample size to accurately depict the features of the broader patient population, which limits the ability to generalize the results across a broader community, thus making the clinical trial results less reliable than clinical trials with a larger number of patients. We plan to enroll larger patient populations in later trials of [ 225 Ac]Ac-AKY-1189. With significantly more patients in future phases of the trial, we may not achieve statistically significant results or the same level of statistical significance, if any, that are observed in any earlier trials. Differences in trial design between early-stage clinical trials and later-stage clinical trials make it difficult to extrapolate the results of earlier clinical trials to later clinical trials. In addition, results in one indication may also not be predictive of results to be expected for the same product candidate in another indication. If we fail to receive positive results in preclinical studies or early-stage clinical trials, or those results are not replicated in later-stage clinical trials of any product candidate or across indications for that product candidate, the development timeline and regulatory approval and commercialization prospects for that product candidate, and, correspondingly, our business, financial condition, results of operations and prospects, would be harmed. The administration of AKY-1189 to patients in South Africa pursuant to Section 21 of the Medicines and Related Substances Act, or MRSA, as authorized by the South African Health Products Regulatory Authority, or SAPHRA, was conducted by a third-party physician. We had limited control and input with respect to the collection of the data from the patients in South Africa conducted pursuant to Section 21 of the MRSA and the manner in which it was conducted and will have limited control with respect to the human imaging data being gathered pursuant to Section 21 of the MSRA. We have relied on the results of the assessment to inform our development of [ 225 Ac]Ac-AKY-1189, and these results may turn out to be incorrect or unreliable. Similarly, we will be relying on the investigator to conduct the human imaging studies in accordance with the applicable protocol, legal, regulatory and scientific standards, and accurately report the results and correctly collect the data. If these results prove to be unreliable, the development of [ 225 Ac]Ac-AKY-1189 may be adversely affected. Interim, topline, or preliminary data from our preclinical studies and clinical trials that we announce or publish from time to time may change as more patient data becomes available or as we make changes to our manufacturing processes and are subject to audit and verification procedures that could result in material changes in the final data. From time to time, we may publicly disclose interim, topline, or preliminary data from our preclinical studies and clinical trials, which is based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the study or trial. Preliminary or interim data from clinical trials are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data becomes available. We also make assumptions, estimations, calculations, and conclusions as part of our analyses of data, and we may not have received or had the opportunity to evaluate all data fully and carefully. Further, modifications or improvements to our manufacturing processes for a therapy may result in changes to the characteristics or behavior of the product candidate that could cause our future product candidates to perform differently and affect the results of our ongoing clinical trials. As a result, other current or the topline results that we report may differ from future results of the same preclinical studies or clinical trials, or different conclusions or considerations may qualify such topline results, once additional data have been received and fully evaluated. Topline data also remain subject to audit and verification procedures that may result in the final data being materially 51 different from the preliminary data we previously published. As a result, topline data should be viewed with caution until the final data are available. Adverse differences between preliminary or interim data and final data could significantly harm our business, financial condition, results of operations and prospects. Additionally, disclosure of preliminary or interim data by us or by our competitors could result in volatility in the price of our common stock. Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions, or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate, and our company in general. If the interim, topline, or preliminary data that we report differ from actual results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain approval for, and commercialize, any of our current or future product candidates may be harmed, which could harm our business, financial condition, results of operations and prospects. Due to the radioactive nature of our product candidates, once manufactured, our product candidates will have time-limited stability, and as a result, we may encounter difficulties with fulfilment and logistics. [ 225 Ac]Ac-AKY-1189 is designed to provide at least four days of stability following radiolabeling, meaning that the patient must intravenously receive our product candidate within four days of its radiolabeling. We anticipate that our future products candidates utilizing 225 Ac, including [ 225 Ac]Ac-AKY-2519, will have similar, limited stable life-span. As such, our product candidates must be manufactured on an as-needed basis, and shipped almost immediately thereafter. Because our product candidates, including [ 225 Ac]Ac-AKY-1189, cannot be “stock-piled” and stored for even a small number of days ahead of shipment, we or any third-party manufacturer must be able to manufacture our product candidates on a rolling basis, and any delays, could result in an immediate and substantial impact on our ability to deliver the product candidate to patients. Any significant delays in delivering product candidates to patients could damage our reputation and result in deviations from our clinical trial protocols, which in turn could affect our ability to advance the clinical development of our product candidates on a timely basis, or at all. In addition, once manufactured, our product candidates must be quickly and safely transported to the applicable clinical trial site. As we scale our operations and enroll larger clinical trials, and prepare for potential commercialization, we will need to scale our shipping abilities. Labor disputes, government restrictions, work stoppages, pandemics, derailments, damage or loss events, adverse weather conditions, other events beyond our control could interrupt or delay transportation, which could result in the loss or damage of our product candidates. Although, we carry insurance to cover material loss or damage to supplies in transit, any insurance policy claims awarded to us may be insufficient to cover our losses or damages. We depend on enrollment and retention of patients in our clinical trials. If we experience delays or difficulties enrolling or retaining patients in our clinical trials, our research and development efforts and business, financial condition, results of operations and prospects could be materially adversely affected. Successful and timely completion of clinical trials will require that we enroll and retain a sufficient number of patient candidates. Any clinical trials we conduct may be subject to delays for a variety of reasons, including as a result of patient enrollment taking longer than anticipated, patient withdrawal, or adverse events. These types of developments could cause us to delay the trial or halt further development. Our clinical trials will compete with other clinical trials that are in the same therapeutic areas as our product candidates, and this competition reduces the number and types of patients available to us, as some patients who might have opted to enroll in our trials may instead opt to enroll in a trial being conducted by one of our competitors. In addition, in the future, we may evaluate our product candidates as first-in-line treatments for which there are other approved treatment alternatives, which may present enrollment challenges. Because the number of qualified clinical investigators and clinical trial sites capable of administering radiopharmaceutical therapies is limited, we expect to conduct some of our clinical trials at the same clinical trial sites that some of our competitors use, which will reduce the number of patients who are available for our clinical trials at such clinical trial sites. Enrollment may also depend in part on the medical community and public’s perception of our product candidates or those of our competitors. Adverse events in our preclinical studies or clinical trials or those of our competitors or of academic researchers or other clinicians utilizing our product candidates under “compassionate use” pathways outside the United States, or similar technologies, even if not ultimately attributable to product candidates we may discover and develop, and the resulting publicity could result in unfavorable public perception and adversely impact our ability to enroll clinical trials. Delays in the completion of any clinical trial of [ 225 Ac]Ac-AKY-1189 for Nectin-4 expressing tumors or our other current or future product candidates will increase our costs, slow down the development and approval process, and delay or potentially jeopardize our ability to commence sales and generate revenue. In addition, some of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of [ 225 Ac]Ac-AKY-1189 or any other current or future product candidates. 52 The commercial success of [ 225 Ac]Ac-AKY-1189, or any of our other current or future products, if approved, will depend upon public perception of radiopharmaceuticals and the degree of their market acceptance by physicians, patients, healthcare payors and others in the medical community. Adverse events in clinical trials of our product candidates, or in clinical trials or other studies conducted by others involving similar products, which may include the same radioisotopes as our product candidates, and the resulting negative publicity, as well as any other adverse events in the field of radiopharmaceuticals that may occur in the future, could result in a decrease in demand for [ 225 Ac]Ac-AKY-1189 for any approved indication or any future product candidates that we may develop. If public perception is influenced by claims that radiopharmaceuticals or specific therapies within radiopharmaceuticals are unsafe, [ 225 Ac]Ac-AKY-1189 or any other current or future product candidates may not be accepted by the general public or the medical community. In particular, the commercial success of our products, if approved, will depend upon, among other things, these products gaining and maintaining acceptance by physicians, patients, third-party payors, and other members of the medical community as efficacious and cost-effective alternatives to competing products and treatments. Even if [ 225 Ac]Ac-AKY-1189, or any other product candidates we develop receive marketing approval by the FDA or other foreign regulatory authority, they may not achieve the level of commercial acceptance and sales experienced by approved beta-emitting therapies, Pluvicto and Lutathera. If any of our products, once approved, do not achieve and maintain an adequate level of acceptance, we may not generate material sales or be able to successfully commercialize such product. The degree of market acceptance of our candidates products, if approved, will depend on a number of factors, including: • our ability to provide acceptable evidence of safety and efficacy; • the prevalence and severity of any side effects in general, and relative to other treatments; • publicity concerning our products or competing products and treatments; • the relative convenience and ease of administration of our products and product candidates, which may require coordination amongst multiple physicians across disciplines for administration; • availability, relative cost and relative efficacy of alternative and competing treatments; • the ability to offer our products for sale at competitive prices; • the willingness of the target patient population to try therapies and of physicians to prescribe these products; • the strength of marketing and distribution support; and • the sufficiency of coverage or reimbursement by third parties. We may develop [ 225 Ac]Ac-AKY-1189, and potentially future product candidates, in combination with other therapies, which exposes us to additional risks. We may develop [ 225 Ac]Ac-AKY-1189, and may develop future product candidates, for use in combination with one or more currently approved cancer therapies. Even if any product candidate we develop was to receive marketing approval or be commercialized for use in combination with other existing therapies, we would continue to be subject to the risks that the FDA or similar foreign regulatory authorities could revoke approval of the therapy used in combination with our product candidate or that safety, efficacy, manufacturing or supply issues could arise with these existing therapies. Combination therapies are commonly used for the treatment of cancer, and we would be subject to similar risks if we develop any of our product candidates for use in combination with other products or for indications other than cancer. This could result in our own products being removed from the market or being less successful commercially. We may also evaluate [ 225 Ac]Ac-AKY-1189 or any other current or future product candidates in combination with one or more other cancer therapies that have not yet been approved for marketing by the FDA or similar foreign regulatory authorities. We will not be able to market and sell [ 225 Ac]Ac-AKY-1189 or any product candidate we develop in combination with any such unapproved cancer therapies that do not ultimately obtain marketing approval. If the FDA or similar foreign regulatory authorities do not approve these other products or revoke their approval of, or if safety, efficacy, manufacturing, or supply issues arise with, the products we choose to evaluate in combination with [ 225 Ac]Ac-AKY-1189 or any product candidate we develop, we may be unable to obtain approval of or market [ 225 Ac]Ac-AKY-1189 or any other current or future product candidate we develop. We may expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success. A key element of our strategy is to apply our development pipeline to address a broad array of cancer targets and new therapeutic areas. The therapeutic discovery activities that we are conducting may not be successful in identifying product candidates that are useful in treating targets in oncology. Our research programs may be unsuccessful in identifying potential 53 product candidates, or our potential product candidates may be shown to have harmful side effects or may have other characteristics that may make the products unmarketable or unlikely to receive regulatory approval. Because we have limited financial and managerial resources, we focus on research programs, therapeutic platforms, and product candidates that we identify for specific indications. Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities. Our spending on current and future research and development programs, therapeutic platforms, and product candidates for specific indications may not yield any commercially viable products. If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may need to 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. We face substantial competition, which may result in others discovering, developing, or commercializing products before or more successfully than we do. The development and commercialization of new radiopharmaceutical products is highly competitive. We face and will continue to face competition from third parties that use radioisotopes and from companies focused on more traditional therapeutic modalities. Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection, and establish collaborative arrangements for research, development, manufacturing, and commercialization of new products. We consider our most direct competitors to be companies developing targeted alpha-based radiopharmaceuticals for the treatment of cancer. There are several companies developing targeted alpha-based radiopharmaceuticals for the treatment of cancer, including Abdera Therapeutics, Actinium Pharmaceuticals, Inc., Alpha9 Oncology, Inc., Artbio AS, Bayer AG, Convergent Therapeutics, Fusion Pharmaceuticals Inc. (acquired by AstraZeneca), Johnson & Johnson, Mariana Oncology, Inc. (acquired by Novartis AG), Perspective Therapeutics, POINT Biopharma Global Inc. (acquired by Eli Lilly), RadioMedix, Inc., RayzeBio, Inc. (acquired by Bristol Myers Squibb) and Telix Pharmaceuticals Limited. These companies are targeting a wide range of solid and hematologic malignancies using various alpha emitting isotopes, including 223 radium, lead-212 and 225 Ac. The first and only approved alpha particle-based therapy is Bayer’s Xofigo ( 223 radium) which is a salt of radium that cannot easily and robustly be attached to a targeting molecule, but naturally localizes to regions where cancer cells are infiltrating bone. Xofigo was approved in 2013 for the treatment of prostate cancer with symptomatic bone metastases. There are several companies with approved beta-emitting radiopharmaceuticals, including Lantheus Holdings, Novartis, Bayer, Sirtex, Boston Scientific and Q BioMed Inc. and other companies developing beta-emitting radiopharmaceuticals, including POINT Biopharma Global, ITM Isotope Technologies Munich SE, Y-Mabs and Telix Pharmaceuticals Limited. The beta emitting isotopes used by these companies include iodine-131, lutetium-177, strontium-89 and yttrium-90. A recently approved beta particle-based radiopharmaceutical is Novartis’ Pluvicto, which was approved by the FDA in 2022 for the treatment of patients with metastatic prostate cancer. Our competitors will also include companies that are or will be developing other treatment methods as well as therapies for the same indications in oncology that we are targeting. In addition to the competitors we face in developing radiopharmaceuticals, we will also face competition in the indications we expect to pursue. In order to compete effectively with these existing therapies, we will need to demonstrate that our therapies are favorable to existing therapeutics and obtain comparable coverage and reimbursement for our product candidates. Many of our current or future competitors have significantly greater financial resources and expertise in research and development, isotope supply chain logistics, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals, obtaining reimbursement for and marketing of approved products than we do. Mergers and acquisitions in the biotechnology, pharmaceutical and diagnostic industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These competitors also compete with us in recruiting and retaining qualified personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we or our collaborators may develop. Our competitors also may obtain FDA or other foreign regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we or our collaborators are able to enter the market. Even if the product candidates we may develop in the future achieve regulatory approval, they may be priced at a significant premium over competitive products if any have been approved by then, resulting in reduced competitiveness. Moreover, technological advances or products developed by our competitors may render our technologies or product candidates we may develop in the future obsolete, less competitive, or not economical. The key competitive factors affecting the success of [ 225 Ac]Ac-AKY-1189 and our other current and future product candidates, if approved, are likely to be their efficacy, safety, convenience, price, the level of generic competition and the availability of reimbursement from government and other third-party payors. 54 The market opportunities for our product candidates may be smaller than we anticipated or may be limited to those patients who are ineligible for or have failed prior treatments. If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected. Our current and future target patient populations are based on our beliefs and estimates regarding the incidence or prevalence of certain types of cancers that may be addressable by our product candidates, which is derived from a variety of sources, including scientific literature and surveys of clinics. Our projections may prove to be incorrect and the number of potential patients may turn out to be lower than expected. Even if we obtain significant market share for our product candidates, because the potential target populations could be small, we may never achieve profitability without obtaining regulatory approval for additional indications, including use of our product candidates for front-line and second-line therapy. We expect to initially seek approval of some of our product candidates, including [ 225 Ac]Ac-AKY-1189 and [ 225 Ac]Ac-AKY-2519, as second-or third-line therapies for patients who have failed other approved treatments. Subsequently, for those product candidates that prove to be sufficiently beneficial, if any, we would expect to seek approval as a second-line therapy and potentially as a front-line therapy, but there is no guarantee that our product candidates, even if approved for third-line therapy, would be approved for second-line or front-line therapy. In addition, we may have to conduct additional clinical trials prior to gaining approval for second-line or front-line therapy. Our company has never commercialized a product candidate and may experience delays or unexpected difficulties in obtaining regulatory approval for our current and future product candidates. Our company has never obtained regulatory approval for, or commercialized, a product. It is possible that the FDA may refuse to accept any or all of our planned BLAs for substantive review or may conclude after review of our data that our application is insufficient to obtain regulatory approval for any product candidates. If the FDA does not approve any of our planned BLAs, it may require that we conduct additional costly clinical trials, preclinical studies or manufacturing validation studies before it will reconsider our applications. Depending on the extent of these or any other FDA-required studies, approval of any BLA or other application that we submit may be significantly delayed, possibly for several years, or may require us to expend more resources than we have available. Any failure or delay in obtaining regulatory approvals would prevent us from commercializing our product candidates, generating revenues and achieving and sustaining profitability. It is also possible that additional studies, if performed and completed, may not be considered sufficient by the FDA to approve any BLA or other application that we submit. If any of these outcomes occur, we may be forced to abandon the development of our product candidates, which would materially adversely affect our business and could potentially cause us to cease operations. We face similar risks for our applications in foreign jurisdictions. We currently have no marketing and sales organization and have no experience in marketing products. If we are unable to establish marketing and sales capabilities or enter into agreements with third parties to market and sell our product candidates, if approved for commercial sale, we may not be able to generate product revenue. We currently have no sales, marketing or distribution capabilities and have no experience in marketing products. We intend to develop an in-house marketing organization and sales force, which will require significant capital expenditures, management resources and time. We will have to compete with other pharmaceutical and biotechnology companies to recruit, hire, train and retain marketing and sales personnel. If we are unable to, or decide not to, establish internal sales, marketing and distribution capabilities, we will pursue collaborative arrangements regarding the sales and marketing of our products, if licensed. However, there can be no assurance that we will be able to establish or maintain such collaborative arrangements, or if we are able to do so, that they will have effective sales forces. Any revenue we receive will depend upon the efforts of such third parties, which may not be successful. We may have little or no control over the marketing and sales efforts of such third parties and our revenue from product sales may be lower than if we had commercialized our product candidates ourselves. We also face competition in our search for third parties to assist us with the sales and marketing efforts of our product candidates. There can be no assurance that we will be able to develop in-house sales and distribution capabilities or establish or maintain relationships with third-party collaborators to commercialize any product in the United States or overseas for which we are able to obtain regulatory approval. We may become exposed to costly and damaging liability claims, either when testing [ 225 Ac]Ac-AKY-1189 or our other current or future product candidates in the clinic or at the commercial stage, and our product liability insurance may not cover all damages from such claims. We are exposed to potential product liability and professional indemnity risks that are inherent in the research, development, manufacturing, marketing, and use of pharmaceutical products. We currently have no products that have been approved for commercial sale, the use of product candidates by us in clinical trials, and the sale of any approved products in the future, may expose us to liability claims, including third-party claims against any of our collaboration partners, some of which we could be contractually obligated to indemnify. These claims might be made by patients that use the product, healthcare providers, pharmaceutical companies, or others selling such products. Any claims against us, regardless of their merit, could be difficult and 55 costly to defend and could materially adversely affect the market for [ 225 Ac]Ac-AKY-1189 or our other current or future product candidates or any prospects for commercialization. Although the clinical trial process is designed to identify and assess potential side effects, it is always possible that a product, even after regulatory approval, may exhibit unforeseen side effects. If [ 225 Ac]Ac-AKY-1189 or any of our other current or future product candidates were to cause adverse side effects during clinical trials or after approval of the product candidate, we may be exposed to substantial liabilities. Physicians and patients may not comply with any warnings that identify known potential adverse effects and patients who should not use [ 225 Ac]Ac-AKY-1189 or our other current or future product candidates. Even successful defense against product liability claims would require significant financial and management resources. Regardless of the merits or eventual outcome, liability claims may result in: • decreased demand for [ 225 Ac]Ac-AKY-1189 or any of our other current or future product candidates; • injury to our reputation; • withdrawal of clinical trial participants; • initiation of investigations by regulators; • costs to defend the related litigation; • a diversion of management’s time and our resources; • substantial monetary awards to trial participants or patients; • product recalls, withdrawals or labeling, marketing or promotional restrictions; • loss of revenue; • exhaustion of any available insurance and our capital resources; • the inability to commercialize any product candidate; and • and a decline in our share price. Although we maintain product liability insurance in the United States, and in other jurisdictions where we have ongoing clinical trials, it is possible that our liabilities could exceed our insurance coverage. We intend to expand our insurance coverage to include the sale of commercial products if we obtain regulatory approval for [ 225 Ac]Ac-AKY-1189 or any of our other current or future product candidates. However, we may be unable to maintain insurance coverage at a reasonable cost or obtain insurance coverage that will be adequate to satisfy any liability that may arise. If a successful product liability claim or series of claims is brought against us for uninsured liabilities or in excess of insured liabilities, our assets may not be sufficient to cover such claims, and our business operations could be impaired. We are party to multiple license and collaboration agreements with significant payment obligations that are contingent upon the occurrence of future events, the timing and likelihood of which are difficult to predict. If we fail to comply with our obligations under these license and collaboration agreements, we could lose rights that are important to our business. Under our license and collaboration agreements, we have payment obligations that are contingent upon future events, such as the achievement of specified development, regulatory and commercial milestones, and in some cases, we are required to make royalty payments in connection with the sales of products developed under those agreements. Although we could be required to make substantial milestone payments under our license and collaboration agreements, we are currently unable to estimate the timing or likelihood of achieving the milestones or making future sales. For further discussion of our obligations under these agreements, see “Business—License and collaboration agreements.” We may be unable to meet our obligations as they become due, especially in the event that multiple milestones are achieved in a short amount of time. If we are unable to meet our obligations when due, it may result in the delay or termination of the research, development or commercialization of the relevant product candidate, and may result in costly litigation or arbitration that diverts management attention and resources away from our day-to-day activities, which may adversely affect our business, financial condition, results of operations and prospects. Risks related to government regulation The development and commercialization of pharmaceutical products is subject to extensive regulation, and the regulatory approval processes of the FDA and comparable foreign authorities are lengthy, time-consuming, and inherently unpredictable. If we are ultimately unable to obtain regulatory approval for [ 225 Ac]Ac-AKY-1189 or any other current or future product candidates, on a timely basis if at all, our business will be substantially harmed. Commencing clinical trials in the United States is subject to acceptance by the FDA of an IND application and finalizing the trial design based on discussions with the FDA. Even after we receive and incorporate guidance from the FDA, the FDA could 56 disagree that we have satisfied their requirements to commence any clinical trial or change their position on the acceptability of our trial design or the clinical endpoints selected, which may require us to complete additional preclinical studies or clinical trials, delay the enrollment of our clinical trials, abandon our clinical development plans or meet stricter approval conditions than we currently expect. There are equivalent processes and risks applicable to clinical trial applications in other countries, including countries in the EU. Furthermore, we have not previously submitted a BLA to the FDA or similar marketing applications to similar foreign regulatory authorities. An BLA must include extensive preclinical and clinical data and supporting information to establish the product candidate’s safety, purity and potency for each desired indication. The BLA must also include significant information regarding the manufacturing controls for the product. We expect the novel nature of our product candidates to create further challenges in obtaining regulatory approval. A BLA must be supported by extensive clinical and preclinical data, as well as extensive information regarding pharmacology, chemistry, manufacturing and controls. Outside the United States, many comparable foreign regulatory authorities employ similar approval processes. [ 225 Ac]Ac-AKY-1189 and any of our current or future product candidates could fail to receive regulatory approval for many reasons, including the following: • the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials; • we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that a product candidate is safe and effective for its proposed indication; • the results of clinical trials may not meet the level of statistical significance required by the FDA or comparable foreign regulatory authorities for approval; • we may be unable to demonstrate that the product candidate’s clinical and other benefits outweigh its safety risks; • the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials; • the data collected from clinical trials of our product candidates may not be sufficient to support the submission of BLA or other submission or to obtain regulatory approval in the United States or elsewhere, or regulatory authorities may not accept a submission due to, among other reasons, the content or formatting of the submission; • the FDA or comparable foreign regulatory authorities may fail to approve our manufacturing processes or facilities or those of third-party manufacturers with whom we contract for clinical and commercial supplies; and • the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval. This lengthy approval process, as well as the unpredictability of clinical trial results, may result in our failing to obtain regulatory approval to market [ 225 Ac]Ac-AKY-1189 or any other current or future product candidates, which would significantly harm our business, financial condition, results of operations and prospects. The FDA and comparable foreign regulatory authorities have substantial discretion in the approval process and determining when or whether regulatory approval will be obtained for [ 225 Ac]Ac-AKY-1189 or any other current or future product candidates. For example, regulatory authorities in various jurisdictions may have differing requirements for, interpretations of and opinions on our preclinical and clinical data. As a result, we may be required to conduct additional preclinical studies, alter our proposed clinical trial designs, or conduct additional clinical trials to satisfy the regulatory authorities in each of the jurisdictions in which we hope to conduct clinical trials and develop and market our products, if approved. Further, even if we believe the data collected from clinical trials of [ 225 Ac]Ac-AKY-1189 or our other current or future product candidates is promising, such data may not be sufficient to support approval by the FDA or any comparable foreign regulatory authority. In addition, even if we were to obtain approval, regulatory authorities may approve [ 225 Ac]Ac-AKY-1189 or any other current or future product candidates for fewer or more limited indications than we request, may not approve the price we intend to charge for our products, may grant approval contingent on the performance of costly post-marketing clinical trials, or may approve 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 [ 225 Ac]Ac-AKY-1189 or any other current or future product candidates. We may seek orphan drug designation for the product candidates we develop, and we may be unsuccessful or may be unable to maintain the benefits associated with orphan drug designation, including the potential for market exclusivity. As part of our business strategy, we may seek orphan drug designation for the product candidates we develop, and we may be unsuccessful. Regulatory authorities in some jurisdictions, including the United States and Europe, may designate drugs and biologics for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may designate a drug or biologic as an orphan drug if it is a drug or biologic intended to treat a rare disease or condition, which is defined as a patient 57 population of fewer than 200,000 individuals annually in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug or biologic will be recovered from sales in the United States. In the United States, orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers. Similarly, in Europe, the European Commission grants orphan drug designation after receiving the opinion of the EMA Committee for Orphan Medicinal Products on an orphan drug designation application. Orphan drug designation is intended to promote the development of drugs and biologics that are intended for the diagnosis, prevention or treatment of life-threatening or chronically debilitating conditions affecting not more than five in 10,000 persons in Europe and for which no satisfactory method of diagnosis, prevention or treatment has been authorized (or the product would be a significant benefit to those affected). Additionally, designation is granted for drugs and biologics intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition and when, without incentives, it is unlikely that sales of the drug or biologic in Europe would be sufficient to justify the necessary investment in developing the drug or biologic. In Europe, orphan drug designation entitles a party to a number of incentives, such as protocol assistance and scientific advice specifically for designated orphan medicines, and potential fee reductions depending on the status of the sponsor. Generally, if a drug or biologic with an orphan drug designation subsequently receives the first marketing approval for the indication for which it has such designation, the drug or biologic is entitled to a period of marketing exclusivity, which precludes the EMA, or the FDA from approving another marketing application for the same drug and for the same indication during the period of exclusivity, except in limited circumstances. The applicable period is seven years in the United States and 10 years in Europe. The European exclusivity period can be reduced to six years if a drug or biologic no longer meets the criteria for orphan drug designation or if the drug or biologic is sufficiently profitable such that market exclusivity is no longer justified. Even if we obtain orphan drug exclusivity for a product candidate, that exclusivity may not effectively protect such product candidate from competition because different therapies can be approved for the same condition and the same therapies can be approved for different conditions but used off-label. Even after an orphan drug is approved, the FDA can subsequently approve the same drug for the same condition if the FDA concludes that the later drug or biologic is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care. In addition, a designated orphan drug may not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received orphan designation. Moreover, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the drug or biologic to meet the needs of patients with the rare disease or condition. Orphan drug designation neither shortens the development time or regulatory review time of a drug or biologic nor gives the drug or biologic any advantage in the regulatory review or approval process. While we may seek orphan drug designation for applicable indications for our current and any future product candidates, we may never receive such designations. Even if we do receive such designation, there is no guarantee that we will enjoy the benefits of that designation. We may seek one or more designations or expedited programs for one or more of our product candidates, but we might not receive such designations or be allowed to proceed on expedited program pathways, and even if we do and proceed on such expedited program pathways in the future, such designations or expedited programs may not lead to a faster development or regulatory review or approval process, and each designation does not increase the likelihood that any of our product candidates will receive marketing approval in the United States. We have received fast track designation for [ 225 Ac]Ac-AKY-1189 for the treatment of adult patients with locally advanced or metastatic UC who had progressed on or after prior systemic therapies and may seek fast track designation for certain of our other product candidates. If a drug is intended for the treatment of a serious or life-threatening condition and nonclinical or clinical data for the drug demonstrates the potential to address an unmet medical need for such a condition, the drug sponsor may apply for fast track designation. The FDA has broad discretion whether or not to grant this designation, so even if we believe a particular product candidate is eligible for this designation, we cannot assure you that the FDA would decide to grant it for any of our other product candidates. Even with fast track designation, we may not experience a faster development process, review or approval compared to conventional FDA procedures. The FDA may withdraw fast track designation if it believes that the designation is no longer supported by data from our clinical development program. Fast track designation alone does not guarantee qualification for the FDA’s priority review procedures. A breakthrough therapy is defined as a drug that is 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 indicates that the drug 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, 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. Product candidates designated as breakthrough therapies by the FDA may also be eligible for priority review and accelerated approval. Designation as a breakthrough therapy is within the discretion of the FDA. 58 Accordingly, even if we believe one of our future product candidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead determine not to make such designation. In any event, the receipt of a breakthrough therapy designation for a product candidate may not result in a faster development process, review or approval compared to therapies considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, even if one or more of our product candidates qualify as breakthrough therapies, the FDA may later decide that such product candidates no longer meet the conditions for qualification or decide that the time period for FDA review or approval will not be shortened. If the FDA determines that a product candidate offers a treatment for a serious condition and, if approved, the product would provide a significant improvement in safety or effectiveness, the FDA may designate the product candidate for priority review. A priority review designation means that the goal for the FDA to review an application is six months, rather than the standard review period of ten months. We may request priority review for our product candidates. The FDA has broad discretion with respect to whether or not to grant priority review status to a product candidate, so even if we believe a particular product candidate is eligible for such designation or status, the FDA may decide not to grant it. Moreover, a priority review designation does not necessarily result in an expedited regulatory review or approval process or necessarily confer any advantage with respect to approval compared to conventional FDA procedures. Receiving priority review from the FDA does not guarantee approval within the six-month review cycle or at all. Even if [ 225 Ac]Ac-AKY-1189 or any of our other current or future product candidates obtains regulatory approval, we will be subject to ongoing obligations and continued regulatory review, which may result in significant additional expense. Additionally, [ 225 Ac]Ac-AKY-1189 or any of our other current or future product candidates, if approved, could be subject to labeling and other restrictions and market withdrawal and we may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our products. If the FDA or a comparable foreign regulatory authority approves [ 225 Ac]Ac-AKY-1189 for any Nectin-4 expressing tumor or any of our other current or future product candidates, the manufacturing facilities and processes, testing, labeling, packaging, distribution, import, export, adverse event reporting, storage, advertising, promotion, and recordkeeping for the product will be subject to extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with cGMP and GCPs for any clinical trials that we conduct post-approval, all of which may result in significant expense and limit our ability to commercialize such products. In addition, any regulatory approvals that we or our partners receive a product candidate may also be subject to limitations on the approved indicated uses for which the product may be marketed or to the conditions of approval, or contain requirements for potentially costly post-marketing testing, including Phase 4 clinical trials, and surveillance to monitor the safety and efficacy of the product candidate. Manufacturers and manufacturers’ facilities are required to comply with extensive FDA and comparable foreign regulatory authority requirements, including ensuring that quality control and manufacturing procedures conform to cGMP regulations. As such, we and our CMOs will be subject to continual review and inspections to assess compliance with cGMP and adherence to commitments made in any approved regulatory application. Accordingly, we and others with whom we work must continue to expend time, money, and effort in all areas of regulatory compliance, including manufacturing, quality control, and distribution. If there are changes in the application of legislation or regulatory policies, or if problems are discovered with a product or our manufacture of a product, or if we or one of our distributors, licensees or co-marketers fails to comply with regulatory requirements, the regulators could take various actions. These include issuing warning letters or untitled letters, imposing fines on us, imposing restrictions on the product or its manufacture, and requiring us to recall or remove the product from the market. The regulators could also suspend any of our preclinical studies and clinical trials or suspend or withdraw our regulatory approvals, requiring us to conduct additional clinical trials, change our product labeling, or submit additional applications for marketing authorization. If any of these events occurs, our ability to sell such product may be impaired, and we may incur substantial additional expense to comply with regulatory requirements, which could materially adversely affect our business, financial condition, results of operations and prospects. In addition, if we have any product candidate approved, our product labeling, advertising, and promotion will be subject to regulatory requirements and continuing regulatory review. In the United States, the FDA and the Federal Trade Commission, or the FTC, strictly regulate the promotional claims that may be made about pharmaceutical products to ensure that any claims about such products are consistent with regulatory approvals, not misleading or false, and adequately substantiated by clinical data. Physicians may use pharmaceutical products off-label in their professional medical judgment, as the FDA does not restrict or regulate a physician’s choice of diagnostic or treatment within the practice of medicine. However, the promotion of a product in a manner that is false, misleading, unsubstantiated, or for unapproved, or off-label, uses may result in enforcement letters, inquiries and investigations, and civil and criminal sanctions by the FDA or the FTC. In particular, a product may not be promoted for uses that are not approved by the FDA as reflected in the product’s approved labeling. If we receive regulatory approval for a product candidate, physicians may nevertheless prescribe it to their patients in a manner that is inconsistent with the approved label. If we are found to have promoted such off-label uses, we may become subject to significant liability. 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 sanctions and may result in false claims litigation under federal and state statutes, which can lead to consent decrees, civil monetary penalties, restitution, criminal fines and imprisonment, and exclusion 59 from participation in Medicare, Medicaid, and other federal and state healthcare programs. The federal government has levied large civil and criminal fines against companies for alleged improper promotion and has enjoined several companies from engaging in off-label promotion. The FDA has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed. Equivalent limitations and penalties are provided in the European Economic Area, or EEA, both at the supranational level and at the national level in the individual EEA countries. Any government investigation of alleged violations of law could require us to expend significant time and resources in response and could generate negative publicity. Any failure to comply with ongoing regulatory requirements may significantly and adversely affect our ability to commercialize and generate revenue from our products, if approved. Failure to comply with EU and EEA countries’ laws that apply to the conduct of clinical trials, manufacturing approval, marketing authorization of medicinal products and marketing of such products, both before and after grant of the marketing authorization, or with other applicable regulatory requirements may result in administrative, civil or criminal penalties. These penalties could include delays or refusal to authorize the conduct of clinical trials, or to grant marketing authorization, product withdrawals and recalls, product seizures, suspension, withdrawal or variation of the marketing authorization, total or partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties. If regulatory sanctions are applied or if regulatory approval is withdrawn, the value of our company and our operating results will be adversely affected. Moreover, the policies of the FDA and of comparable foreign regulatory authorities may change and additional government regulations may be enacted that could prevent, limit, or delay regulatory approval of [ 225 Ac]Ac-AKY-1189 or any of our other or future product candidates. As an example, the regulatory landscape related to clinical trials in the EEA recently evolved. The EU Clinical Trials Regulation, or CTR, which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022. The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each EEA country, leading to a single decision for each EEA country. The assessment procedure for the authorization of clinical trials has been harmonized as well, including a joint assessment by all EEA countries concerned, and a separate assessment by each EEA country with respect to specific requirements related to its own territory, including ethics rules. Each EEA country’s decision is communicated to the sponsor via the centralized EU portal. Once the clinical trial approved, clinical study development may proceed. The CTR foresees a three-year transition period. The extent to which ongoing and new clinical trials will be governed by the CTR varies. For clinical trials in relation to which application for approval was made on the basis of the Clinical Trials Directive before January 31, 2022, the Clinical Trials Directive will continue to apply on a transitional basis for three years. Additionally, sponsors could choose to submit a clinical trial application under either the Clinical Trials Directive or the CTR until January 31, 2023. Where these trials were authorized on the basis of the Clinical Trials Directive, they will be governed by the Clinical Trials Directive until January 31, 2025. Commencing on February 1, 2025, all ongoing trials are subject to the provisions of the CTR. The CTR will apply to clinical trials from an earlier date if the clinical trial has already transitioned to the CTR framework. Compliance with the CTR requirements by us and our third-party service providers, such as CROs, may impact our developments plans. We cannot predict the likelihood, nature, or extent of government regulation that may arise from future legislation or administrative or executive action, either in the United States or abroad. In addition, if we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any regulatory approval that we may have obtained and we may not achieve or sustain profitability. Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not mean that we will be successful in obtaining regulatory approval of our product candidates in other jurisdictions. Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not guarantee that we will be able to obtain or maintain regulatory approval in any other jurisdiction, while a failure or delay in obtaining regulatory approval in one jurisdiction may have a negative effect on the regulatory approval process in others. For example, even if the FDA grants marketing approval of a product candidate, similar foreign regulatory authorities must also approve the manufacturing, marketing and promotion of the product candidate in those countries. Approval and licensure procedures vary among jurisdictions and can involve requirements and administrative review periods different from, and greater than, those in the United States, including additional preclinical studies or clinical trials as clinical trials conducted in one jurisdiction may not be accepted by regulatory authorities in other jurisdictions. In many jurisdictions outside the United States, a product candidate must be approved for reimbursement before it can be approved for sale in that jurisdiction. In some cases, the price that we intend to charge for our products is also subject to approval. 60 We may also submit marketing applications in other countries. Regulatory authorities in jurisdictions outside of the United States have requirements for approval of product candidates with which we must comply prior to marketing in those jurisdictions. Obtaining similar foreign regulatory approvals and compliance with similar foreign regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction of our products in certain countries. If we fail to comply with the regulatory requirements in international markets and/or receive applicable marketing approvals, our target market will be reduced and our ability to realize the full market potential of our product candidates will be harmed. Disruptions at the FDA and other government agencies and foreign regulatory authorities, including those caused by funding shortages or global health concerns could hinder their ability to hire, retain, or deploy key leadership and other personnel, or otherwise prevent new or modified drugs from being developed, approved, or commercialized in a timely manner or at all, which could negatively impact our business. The ability of the FDA or comparable foreign regulatory authorities to review and approve new drugs can be affected by a variety of factors, including government budget reductions in force, and funding levels, statutory, regulatory, and policy changes, the FDA’s or comparable foreign regulatory authorities’ ability to hire and retain key personnel and accept the payment of user fees, pandemics and other public health crises, and other events that may otherwise affect the FDA’s or comparable foreign regulatory authorities’ ability to perform routine functions. Average review times at the FDA have fluctuated in recent years as a result. In addition, government funding of other government agencies that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable. Recent disruptions at the FDA and other agencies may also slow the time necessary for new drugs or modifications to approved drugs to be reviewed and/or approved by necessary regulatory authorities, which would adversely affect our business. For example, in recent years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA, have had to furlough critical employees and stop critical activities. In addition, the current U.S. presidential administration has issued certain policies and executive orders directed towards reducing the employee headcount and costs associated with U.S. administrative agencies, including the FDA, and it remains unclear the degree to which these efforts may limit or otherwise adversely affect the FDA’s ability to conduct routine activities. Separately, in response to the COVID-19 pandemic, the FDA postponed most inspections of domestic and foreign manufacturing facilities at various points. If any future prolonged government shutdown occurs, or if renewed global health concerns, funding shortages or staffing limitations 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, financial condition, results of operations and prospects. We are currently, and may in the future, conduct clinical trials for product candidates outside the United States, and the FDA and comparable foreign regulatory authorities may not accept data from such trials. We may in the future choose to conduct one or more additional clinical trials outside the United States, including in the EU, South Africa, Australia and/or Asia. The acceptance of study data from clinical trials conducted outside the United States or another jurisdiction by the FDA or comparable foreign regulatory authority may be subject to certain conditions or may not be accepted at all. In cases where data from foreign clinical trials are intended to serve as the basis for regulatory approval in the United States, the FDA will generally not approve the application based on foreign data alone unless: (i) the data is applicable to the U.S. population and U.S. medical practice; and (ii) the trials were performed by clinical investigators of recognized competence and pursuant to GCP regulations. Additionally, the FDA’s clinical trial requirements, including sufficient size of patient populations and statistical powering, must be met. Many foreign regulatory authorities have similar approval requirements. In addition, such foreign trials would be subject to the applicable local laws of the foreign jurisdictions where the trials are conducted. There can be no assurance that the FDA or any comparable foreign regulatory authority will accept data from trials conducted outside of the United States or the applicable jurisdiction. If the FDA or any comparable foreign regulatory authority does not accept such data, it would result in the need for additional trials, which could be costly and time-consuming, and which may result in product candidates that we may develop not receiving approval for commercialization in such jurisdiction. Our business operations and current and future relationships with healthcare professionals, principal investigators, consultants, vendors, customers, and third-party payors in the United States and elsewhere are subject, directly or indirectly, to applicable anti-kickback, fraud and abuse, false claims, physician payment transparency, health information privacy and security and other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings. Healthcare providers, healthcare facilities and institutions, and third-party payors in the United States and elsewhere will play a primary role in the recommendation and prescription of any product candidates for which we obtain regulatory approval. Our future arrangements with healthcare professionals, healthcare facilities and institutions, principal investigators, consultants, customers, and third-party payors may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations, including, without limitation, the federal Anti-Kickback Statute and the federal False Claims Act, or the FCA, which may constrain 61 the business or financial arrangements and relationships through which we research, sell, market, and distribute any product candidates for which we obtain regulatory approval. In addition, we may be subject to physician payment transparency laws and regulation by the federal government and by the states and foreign jurisdictions in which we conduct our business. The applicable federal, state, and foreign healthcare laws and regulations that affect our ability to operate include, but are not limited to, the following: • the federal Anti-Kickback Statute, which prohibits, among other things, persons or entities from knowingly and willfully soliciting, offering, 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, lease, order or recommendation of, any good, facility, item or service, for which payment may be made, in whole or in part, under any U.S. federal healthcare program, such as Medicare and Medicaid. The term “remuneration” has been broadly interpreted to include anything of value. The federal Anti-Kickback Statute has also been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other hand. There are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution, but the exceptions and safe harbors are drawn narrowly and require strict compliance in order to offer protection. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • the U.S. federal civil and criminal false claims laws, including without limitation, the civil FCA, which can be enforced by private citizens on behalf of the U.S. federal government through civil whistleblower or qui tam actions, and the federal civil monetary penalties law which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, to the U.S. federal government, claims for payment or approval that are false or fraudulent, knowingly making, using, or causing to be made or used, a false record or statement material to a false or fraudulent claim, or from knowingly making a false statement to avoid, decrease, or conceal an obligation to pay money to the U.S. federal government. Pharmaceutical manufacturers can cause false claims to be presented to the U.S. federal government by, among other things, engaging in impermissible marketing practices, such as the off-label promotion of a drug for an indication for which it has not received FDA approval. Further, pharmaceutical manufacturers can be held liable under the civil 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 including items and services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil FCA; • the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal and civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing, or covering up a material fact or making any materially false statement, in connection with the delivery of, or payment for, healthcare benefits, items, or services. Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the healthcare fraud statute implemented under HIPAA or specific intent to violate it in order to have committed a violation; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, impose obligations on certain healthcare providers, health plans and healthcare clearinghouses, known as covered entities, as well as their business associates and their subcontractors that perform certain services involving the storage, use or disclosure of individually identifiable health information, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information and require notification to affected individuals and regulatory authorities of certain breaches of security of individually identifiable health information. HITECH increased the civil and criminal penalties that may be imposed against covered entities, business associates and possibly other persons and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions. In addition, many state laws govern the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, and often are not preempted by HIPAA; • the U.S. Federal Food, Drug, and Cosmetic Act, or the FDCA, which prohibits, among other things, the adulteration or misbranding of drugs, biologics, and medical devices; • the federal and state laws that require pharmaceutical manufacturers to report certain calculated drug prices to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement under government healthcare programs; • the U.S. Physician Payments Sunshine Act and its implementing regulations, which requires, among other things, certain manufacturers of drugs, devices, biologics, and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare and Medicaid Services, or CMS, information related to certain payments and other transfers of value physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare professionals (such as physician assistants and nurse practitioners), and teaching hospitals, as well as ownership and investment interests held by such physicians and their immediate family members; 62 • analogous U.S. state laws and regulations, including: state anti-kickback and false claims laws, which may apply to our business practices, including but not limited to, research, distribution, sales and marketing arrangements, and claims involving healthcare items or services reimbursed by any third-party payor, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the U.S. federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws and regulations that require drug manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; and state and local laws requiring the registration of pharmaceutical sales representatives; and • similar healthcare laws and regulations in foreign jurisdictions, including reporting requirements detailing interactions with and payments to healthcare providers. Outside the United States, interactions between pharmaceutical companies and healthcare professionals are also governed by strict laws, such as national anti-bribery laws of European countries, national sunshine rules, regulations, industry self-regulation codes of conduct and physicians’ codes of professional conduct. Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment. Ensuring that our internal operations and future business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs. It is not always possible to identify and deter employee misconduct or business non-compliance, and the precautions we take to detect and prevent inappropriate conduct may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations. Efforts to ensure that our business arrangements will comply with applicable healthcare laws may involve substantial costs. We have entered into consulting and scientific advisory board arrangements with physicians and other healthcare providers, including some who could influence the use of [ 225 Ac]Ac-AKY-1189 of any of our other current or future product candidates, if approved. Compensation under some of these arrangements includes the provision of stock or stock options in addition to cash consideration. Because of the complex and far-reaching nature of these laws, it is possible that if our products are commercialized, governmental authorities could conclude that our business practices do not comply with current or future statutes, regulations, agency guidance or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to significant penalties, including civil, criminal, and administrative penalties, damages, fines, exclusion from government-funded healthcare programs, such as Medicare and Medicaid, or similar programs in other countries or jurisdictions, integrity oversight and reporting obligations to resolve allegations of non-compliance, disgorgement, imprisonment, contractual damages, reputational harm, diminished profits, and the curtailment or restructuring of our operations. If any of the physicians or other providers or entities with whom we expect to do business are found to be in violation of applicable laws, they may be subject to significant criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs and imprisonment, which could affect our ability to operate our business. Further, defending against any such actions can be costly, time-consuming and may require significant personnel resources. Therefore, even if we are successful in defending against any such actions that may be brought against us, our business may be impaired. Healthcare policy changes may have a material adverse effect on our business, financial condition, results of operations and prospects. The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively, the ACA, enacted in March 2010, made several substantial changes in the way healthcare is financed by both governmental and private insurers, and significantly impacted the U.S. pharmaceutical industry. Some ways in which the ACA may significantly impact our business include provisions regarding coordination and promotion of research on comparative clinical effectiveness of different technologies and procedures, initiatives to revise Medicare payment methodologies, and initiatives to promote quality indicators in payment methodologies. 63 There have been legal and political challenges to certain aspects of the ACA. For example, on June 17, 2021, the U.S. Supreme Court dismissed a challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress. Prior to the U.S. Supreme Court ruling, on January 28, 2021, President Biden issued an executive order to initiate a special enrollment period from February 15, 2021, through August 15, 2021 for purposes of obtaining health insurance coverage through the ACA marketplace. The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA. Further, on August 16, 2022, President Biden signed the Inflation Reduction Act of 2022, or IRA, into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025. The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program. It is possible that the ACA will be subject to judicial or Congressional challenges in the future. It is unclear how any such challenges and current or evolving federal policies regarding healthcare reform measures will impact the ACA or our business. Since the ACA’s passage, legislative changes to the ACA have been proposed and adopted. On July 4, 2025, the annual reconciliation bill, the “One Big Beautiful Bill Act,” or OBBBA, was signed into law which is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program. OBBBA also narrows access to ACA marketplace exchange enrollment and declines to extend the ACA’s enhanced advanced premium tax credits, set to expire in 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance. Additionally, under the sequestration required by the Budget Control Act of 2011, beginning April 1, 2013, Medicare payments to providers were reduced, which will remain in effect through 2032 unless additional Congressional action is taken. On March 11, 2021, the American Rescue Plan Act of 2021 was signed into law, which eliminated the statutory cap on the Medicaid drug rebate effective January 1, 2024. The rebate was previously capped at 100% of a drug’s average manufacturer price. Recently, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed drugs, which has resulted in several presidential executive orders, Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products. At the federal level, in July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs. In response to Biden’s executive order, on September 9, 2021, the U.S. Department of Health and Human Services, or HHS, released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles. Further, the IRA, among other things (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation. These provisions began to take effect progressively in fiscal year 2023, although the drug price negotiation program is currently subject to legal challenges. HHS has and will continue to issue and update guidance as these programs are implemented. It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry. In addition, in response to the Biden administration’s October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the Center for Medicare and Medicaid Innovation which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care. It is unclear whether the models will be utilized in any health reform measures in the future. At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological drug pricing, including price or patient reimbursement constraints, discounts, restrictions on certain drug access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Our ability to develop and market new drug products may be impacted if litigation challenging the FDA’s approval of another company’s drug continues. In April 2023, the U.S. District Court for the Northern District of Texas invalidated the approval by the FDA of mifepristone, a drug product, which was originally approved in 2000, and whose distribution is governed by various measures adopted under a REMS. The Court of Appeals for the Fifth Circuit declined to order the removal of mifepristone from the market but did hold that plaintiffs were likely to prevail in their claim that changes allowing for expanded access of mifepristone, which the FDA authorized in 2016 and 2021, were arbitrary and capricious. In June 2024, the Supreme Court reversed and remanded that decision after unanimously finding that the plaintiffs did not have standing to bring this legal action against the FDA. Depending on the outcome of this litigation, if it continues, our ability to develop [ 225 Ac]Ac-AKY-1189 or future product candidates we may develop may be at risk and could be delayed, undermined or subject to protracted litigation. Finally, we could be adversely affected by several significant administrative law cases decided by the U.S. Supreme Court in 2024. In Loper Bright Enterprises v. Raimondo , for example, the court overruled Chevron U.S.A., Inc. v. Natural Resources Defense Council, Inc. , which for 40 years required federal courts to defer to permissible agency interpretations of statutes that are silent or ambiguous on a particular topic. The U.S. Supreme Court stripped federal agencies of this presumptive deference and held that courts must exercise their independent judgment when deciding whether an agency such as FDA acted within its statutory authority under the Administrative Procedure Act, or the APA. Additionally, in Corner Post, Inc. v. Board of Governors of the Federal Reserve System , the court held 64 that actions to challenge a federal regulation under the APA can be initiated within six years of the date of injury to the plaintiff, rather than the date the rule is finalized. The decision appears to give prospective plaintiffs a personal statute of limitations to challenge longstanding agency regulations. These decisions could introduce additional uncertainty into the regulatory process and may result in additional legal challenges to actions taken by federal regulatory agencies, including the FDA and the CMS that we rely on. In addition to potential changes to regulations as a result of legal challenges, these decisions may result in increased regulatory uncertainty and delays and other impacts, any of which could adversely impact our business and operations. Furthermore, recent changes to the leadership of federal agencies like HHS, CMS and FDA can lead to new policies and regulations that can have a material impact on our industry and business operations. Many EEA countries periodically review their reimbursement procedures for medicinal products, which could have an adverse impact on reimbursement status. We expect that legislators, policymakers and healthcare insurance funds in the EEA countries will continue to propose and implement cost-containing measures, such as lower maximum prices, lower or lack of reimbursement coverage and incentives to use cheaper, usually generic, products as an alternative to branded products, and/or branded products available through parallel import to keep healthcare costs down. Moreover, in order to obtain reimbursement for our products in some European countries, including some EEA countries, we may be required to compile additional data comparing the cost-effectiveness of our products to other available therapies. Health Technology Assessment, or HTA, of medicinal products is becoming an increasingly common part of the pricing and reimbursement procedures in some EEA countries, including those representing the larger markets. The HTA process is the procedure to assess therapeutic, economic and societal impact of a given medicinal product in the national healthcare systems of the individual country. The outcome of an HTA will often influence the pricing and reimbursement status granted to these medicinal products by the competent authorities of individual EEA countries. The extent to which pricing and reimbursement decisions are influenced by the HTA of the specific medicinal product currently varies between EEA countries. In December 2021, Regulation No 2021/2282 on HTA amending Directive 2011/24/EU, was adopted in the EU. This Regulation, which entered into force in January 2022 and will apply as of January 2025, is intended to boost cooperation among EEA countries in assessing health technologies, including new medicinal products, and providing the basis for cooperation at EEA level for joint clinical assessments in these areas. The Regulation foresees a three-year transitional period and will permit EEA countries to use common HTA tools, methodologies, and procedures across the EEA, working together in four main areas, including joint clinical assessment of the innovative health technologies with the most potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas. Individual EEA countries will continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technologies, and making decisions on pricing and reimbursement. If we are unable to maintain favorable pricing and reimbursement status in EEA countries for product candidates that we may successfully develop and for which we may obtain regulatory approval, any anticipated revenue from and growth prospects for those products in the EEA could be negatively affected. Legislators, policymakers and healthcare insurance funds in the EEA may continue to propose and implement cost-containing measures to keep healthcare costs down; particularly due to the financial strain that the COVID-19 pandemic placed on national healthcare systems of the EEA countries. These measures could include limitations on the prices we would be able to charge for product candidates that we may successfully develop and for which we may obtain regulatory approval or the level of reimbursement available for these products from governmental authorities or third-party payors. Further, an increasing number of EEA and other foreign countries use prices for medicinal products established in other countries as “reference prices” to help determine the price of the product in their own territory. Consequently, a downward trend in prices of medicinal products in some countries could contribute to similar downward trends elsewhere. We cannot predict whether future healthcare initiatives will be implemented at the federal or state level, supranational or national level, or how any future legislation or regulation may affect us, any of which may have a materially adverse effect on our business, financial condition, results of operations and prospects. Even if we are able to commercialize a product candidate, coverage and adequate reimbursement may not be available or such product candidate may become subject to unfavorable pricing regulations or third-party coverage and reimbursement policies, which would harm our business. The regulations that govern regulatory approvals, pricing, and reimbursement for product products vary widely from country to country. Some countries require approval of the sale price of a drug product before it can be marketed or may require us or our collaborators to conduct clinical trials that compare the cost-effectiveness of our product candidates to other therapies to obtain reimbursement or pricing approval. In many countries, the pricing review period begins after regulatory approval is granted. In some foreign markets, prescription drug product pricing remains subject to continuing governmental control even after initial approval is granted. As a result, we might obtain regulatory approval for a product in a particular country, but then be subject to price regulations that delay our commercial launch of the product, possibly for lengthy time periods, and negatively impact the revenue we are able to generate from the sale of the product in that country. Adverse pricing limitations may hinder our ability to 65 recoup our investment in one or more product candidates, even if [ 225 Ac]Ac-AKY-1189 or any of our future product candidates obtain regulatory approval. Our ability to commercialize any products successfully also will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from third-party payors, such as government authorities, private health insurers, and other organizations. Even if we succeed in bringing one or more products to market, these products may not be considered cost-effective, and the amount reimbursed for any products may be insufficient to allow us to sell our products on a competitive basis. Because our programs are in the early stages of development, we are unable at this time to determine their cost effectiveness or the likely level or method of coverage and reimbursement. Increasingly, the third-party payors who reimburse patients or healthcare providers are requiring that drug companies provide them with predetermined discounts from list prices, and are seeking to reduce the prices charged or the amounts reimbursed for drug products. Moreover, no uniform policy requirement for coverage and reimbursement for drugs exists among third-party payors in the United States, which may result in significant variations in coverage and reimbursement from payor to payor. Even if favorable coverage and reimbursement status is attained for one or more drug products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future. If the price we are able to charge for any products we develop, or the coverage and reimbursement provided for such products, is inadequate in light of our development and other costs, our return on investment could be affected adversely. The continuing efforts of the government, insurance companies, managed care organizations, and other payors of healthcare services to contain or reduce costs of healthcare and/or impose price controls may adversely affect: • the demand for [ 225 Ac]Ac-AKY-1189 or any of our other current or future product candidates, if we obtain regulatory approval; • our ability to set a price that we believe is fair for our products; • our ability to obtain coverage and reimbursement approval for a product; • our ability to generate revenue and achieve or maintain profitability; • the level of taxes that we are required to pay; and • the availability of capital. Our inability to promptly obtain and maintain coverage and adequate reimbursement from both third-party payors for the product candidates that we may develop and for which we obtain regulatory approval could adversely affect our business, financial condition, results of operations, and prospects. We and our collaborators and our third-party service providers are subject to a variety of stringent and evolving U.S. and foreign laws, regulations, rules, contractual obligations, policies and industry standards related to data privacy and cybersecurity, which could increase compliance costs, and our actual or perceived failure to comply therewith could subject us to regulatory investigations or actions, litigation, fines or penalties, disruptions of our business operation, reputational harm, loss of revenue or profits, and other adverse business consequences. We process a large quantity of sensitive information, including proprietary and confidential business information and other personal information, and we and our collaborators and third-party service providers are subject to various federal, state, local and foreign data privacy and cybersecurity laws, rules and regulations relating to the privacy, security and processing of personal information. The global data privacy and cybersecurity landscape is rapidly evolving, and we and our collaborators and third-party service providers may be affected by or subject to new, amended, or existing laws, rules and regulations, including as our operations continue to expand or if we operate in foreign jurisdictions. These laws, rules and regulations may be subject to differing interpretations, which adds to the complexity of processing personal information. Guidance on implementation and compliance practices are often updated or otherwise revised. This evolution may create uncertainty in our business, affect our ability to operate in certain jurisdictions or to collect, store, transfer, use, share or otherwise process personal information, necessitate the acceptance of more onerous obligations in our contracts, result in liability or impose additional costs on us. If we fail or are perceived to have failed to comply with these laws, rules and regulations, we may be subject to litigation, regulatory investigations, enforcement notices, enforcement actions, fines, imprisonment of company officials and public censure, claims for damages by affected individuals, and criminal or civil penalties, as well as negative publicity, reputational harm, loss of goodwill and a potential loss of business, any of which could have a material adverse effect on our business, financial condition, results of operations and prospects. 66 In the United States, numerous federal, state and local laws, rules and regulations, including state data breach notification laws and federal and state data privacy laws, rules and regulations that govern the collection, use, disclosure, protection, transfer and other processing of health information and other personal information apply to our operations and the operations of our collaborators and third-party service providers. Each of these laws, rules and regulations is subject to varying interpretations and constantly evolving. For example, HIPAA, as amended by HITECH, and regulations promulgated thereunder impose certain obligations with respect to safeguarding the privacy, security, transmission and other processing of individually identifiable health information on “covered entities,” and their respective “business associates,” as well as their covered subcontractors, that perform services for them. Depending on the facts and circumstances, we could be subject to significant penalties if we violate HIPAA. For example, under HIPAA, we could potentially face substantial criminal or civil penalties if we knowingly receive protected health information from a HIPAA-covered healthcare provider or research institution that has not satisfied HIPAA’s requirements for disclosure of such protected health information, or otherwise violate applicable HIPAA requirements related to the protection of such information. Moreover, determining whether protected health information has been handled in compliance with applicable privacy standards and our contractual obligations with third parties can be complex and may be subject to changing interpretation. If we are unable to properly protect the privacy and security of protected health information, we could be found to have breached our contracts. The HHS has the discretion to impose penalties without attempting to first resolve violations. HHS enforcement activity can result in financial liability and reputational harm, and responses to such enforcement activity can consume significant internal resources. Even when HIPAA does not apply, failing to take appropriate steps to keep consumers’ personal information secure may constitute a violation of the Federal Trade Commission Act. The FTC expects a company’s data security measures to be reasonable and appropriate in light of the sensitivity and volume of consumer information it holds, the size and complexity of its business and the cost of available tools to improve security and reduce vulnerabilities. Individually identifiable health information is considered sensitive data that merits stronger safeguards. In connection with our clinical trials, we may maintain sensitive identifiable personal information, including health information, that we receive throughout the clinical trial process, during our research collaborations, and directly from individuals (or their healthcare providers) who enroll in our patient assistance programs. As such, we may become subject to further obligations under HIPAA. In addition, our collection of personal information generally may subject us and our collaborators and third-party service providers to state data privacy laws governing the processing of personal information, including requiring us to reasonably protect certain types of personal information we hold or to otherwise comply with certain specified cybersecurity requirements with respect to personal information and requiring notification of affected individuals and state regulators in the event of a breach of such personal information in certain instances. For example, these state laws include the California Consumer Privacy Act, as amended by the California Privacy Rights Act, or collectively the CCPA, and applies to personal information of consumers, business representatives and employees that are California residents and requires covered businesses to make disclosures to consumers about their data collection, use and sharing practices, allows consumers to opt out of certain data sharing with third parties and provides a cause of action for data breaches. The CCPA provides for significant civil penalties of up to $7,500 per violation as well as a private right of action for certain data breaches and statutory damages. Although there are limited exemptions for clinical trial data and some other health data under the CCPA, the CCPA and other similar laws may impact our business activities and increase our compliance costs. Additionally, the California Privacy Rights Act, effective in most material respects as of January 1, 2023, expanded data privacy and cybersecurity compliance requirements and consumers’ rights under the CCPA including by, among other things, giving California residents the ability to correct their personal information and limit use of certain sensitive personal information, establishing restrictions on the retention of personal information, expanding the types of data breaches subject to the CCPA’s private right of action, and establishing a new California Privacy Protection Agency to implement and enforce the law. Other states, including but not limited to Virginia, Colorado, Utah, and Connecticut, have also passed comprehensive privacy laws, and similar laws are being considered in several other states (including Washington, which enacted the My Health, My Data Act in 2023), as well as at the federal and local levels. While many of these states, like California, also exempt some data processed in the context of clinical trials, these laws could have potentially conflicting requirements that further complicate compliance efforts, and increase legal risk and compliance costs for us, and the third parties upon whom we rely. In addition, all 50 U.S. states and the District of Columbia have enacted breach notification laws that may require us to notify patients, employees or regulators in the event of unauthorized access to or disclosure of personal or confidential information experienced by us or our collaborators or third-party service providers. These laws are not consistent, and compliance in the event of a widespread data breach is difficult and may be costly. Moreover, states have been frequently amending existing laws, requiring attention to changing regulatory requirements. We also may be contractually required to notify patients or other counterparties of a security breach. In addition to government regulation, privacy advocates and industry groups have and may in the future propose self-regulatory standards from time to time. These and other industry standards may legally or contractually apply to us, or we may elect to comply with such standards. Any clinical trial programs and research collaborations that we engage in outside the United States may implicate international data protection laws, including, in Europe, the General Data Protection Regulation, or GDPR, and the United Kingdom’s GDPR, combining the GDPR and the UK’s Data Protection Act of 2018, or the UK GDPR. The GDPR and UK GDPR govern the collection, use, disclosure, transfer or other processing of personal data of individuals within the EEA and UK and impose stringent operational requirements for data processors and controllers of personal data. For example, the GDPR and UK GDPR impose onerous 67 accountability obligations requiring data controllers and processors to maintain a record of their data processing and policies. The GDPR and UK GDPR also impose certain other onerous obligations, including obligations for controllers and processors to appoint data protection officers in certain circumstances, increased transparency obligations to data subjects for controllers, obligations to honor increased rights for data subjects, and obligations to implement certain technical and organizational safeguards to protect the security and confidentiality of personal data. The GDPR and UK GDPR also provide that EEA member states and the UK make their own further laws, rules and regulations to introduce specific requirements related to the processing of “special categories of personal data,” including personal data related to health, biometric data used for unique identification purposes and genetic information, as well as personal data related to criminal offences or convictions. This fact may lead to greater divergence on the law that applies to the processing of such data types across the EEA and the UK, compliance with which, as and where applicable, may increase our costs and could increase our overall compliance risk. Such member state specific regulations could limit our ability to collect, use and share data in the context of any future EEA or UK establishments (regardless of where any processing in question occurs). Among other things, the GDPR and UK GDPR require detailed notices for clinical trial subjects and investigators as well as the security of personal information, and notification of data processing obligations or security incidents to appropriate data protection authorities or data subjects. In addition, the GDPR and UK GDPR materially expanded the definition of what constitutes personal data (including, for example, by expressly clarifying that the GDPR applies to “pseudonymized” and key-coded data). Since January 1, 2021, when the transitional period following the exit of the UK from the EU, or Brexit, expired, companies required to comply with the GDPR are also required to comply with the UK GDPR, which exposes these companies to two parallel regimes, each of which authorizes similar fines and may subject them to increased compliance risk based on differing, and potentially inconsistent or conflicting, interpretation and enforcement by regulators and authorities (particularly, if the laws are amended in the future in divergent ways). While the GDPR and the UK GDPR remain substantially similar for the time being, the government of the UK has adopted reforms to its data privacy and cybersecurity legal framework in its Data Use and Access Act 2025, which became law on June 19, 2025 (phasing in between June 2025 and June 2026) and will introduce significant changes from the GDPR. This may lead to additional compliance costs and could increase overall risk exposure as businesses may no longer be able to take a unified approach across the EEA and the UK, and such businesses may need to amend their processes and procedures to align with the new framework. Implementing mechanisms to endeavor to ensure compliance with the GDPR and the UK GDPR may be onerous and expose businesses to divergent parallel regimes that may be subject to potentially different interpretations and enforcement actions for certain violations and related uncertainty. With respect to transfers of personal data from the EEA, on June 28, 2021, the European Commission issued an adequacy decision in respect of the UK’s data protection framework, enabling data transfers from EU member states to the UK to continue without requiring organizations to put in place contractual or other measures in order to lawfully transfer personal data between the territories. However, the UK adequacy decision will automatically expire in December 2031 unless the European Commission re-assesses and renews or extends that decision and remains under review (and may be modified or revoked) by the Commission during this period. In addition, transfers of personal data from the UK to other countries, including the EEA, are subject to specific transfer rules under the UK regime. The GDPR and UK GDPR impose substantial fines for breaches and violations (up to the greater of €20 million or 4% of consolidated annual worldwide gross revenue under the GDPR or GBP 17.5 million under the UK GDPR). In addition to administrative fines, a wide variety of other potential enforcement powers are available to competent supervisory authorities in respect of potential and suspected violations of the GDPR or the UK GDPR, including extensive audit and inspection rights, and powers to order temporary or permanent bans on all or some processing of personal data carried out by non-compliant actors The GDPR and UK GDPR also confer a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies and obtain compensation for damages resulting from violations of the GDPR or the UK GDPR. Further, the exit of the UK from the EU and ongoing developments in the UK have created uncertainty regarding data protection regulation in the UK. Certain legal developments in Europe have created complexity and uncertainty regarding transfers of personal data from the EEA to the United States, which will affect us if we begin to transfer personal data from the EEA to other jurisdictions. In July 2023, the European Commission adopted an adequacy decision in relation to the new EU-U.S. Data Privacy Framework, or DPF, rendering the DPF effective as a GDPR transfer mechanism for personal data transferred from the EEA to the United States by United States entities self-certified under the DPF. However, the DPF adequacy decisions do not foreclose, and are likely to face, future legal challenges and the ongoing legal uncertainty with respect to international data transfers may increase our costs and our ability to efficiently process personal data from the EEA. Other data transfer mechanisms such as the Standard Contractual Clauses approved by the European Commission have faced challenges in European courts, may require additional risk analysis and supplemental measures to be used, and may be challenged, suspended or invalidated. Loss of our ability to lawfully transfer personal data out of the EEA and UK to the United States or any other jurisdictions may require us to increase our data processing capabilities in the EEA and UK at significant expense. If we are otherwise unable to transfer personal data between and among countries and regions in which we operate, it could affect the manner in which we perform our operations or provide our services, the geographical location or segregation of our relevant systems and operations, and adversely affect our financial results. These international laws, rules and regulations may apply not only to us, but also to our collaborators, vendors or other third-party service providers that store 68 or otherwise process personal data on our behalf, such as information technology vendors, and any of the foregoing limitations could impact our ability to work with such collaborators or third-party service providers in certain jurisdictions. We are bound by contractual obligations related to data privacy and cybersecurity, and our efforts to comply with such obligations may not be successful. For example, certain data privacy laws, such as the EU GDPR, the UK GDPR and the CCPA, require our customers to impose specific contractual restrictions on their service providers. We publish privacy policies, marketing materials and other statements, such as compliance with certain certifications or self-regulatory principles, regarding data privacy and cybersecurity. If these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators or other adverse consequences. Obligations related to data privacy and cybersecurity are quickly changing, becoming increasingly stringent, and creating regulatory uncertainty. Additionally, these obligations may be subject to differing applications and interpretations, which may be inconsistent or conflicting among jurisdictions. We are likely to be required to expend significant capital and other resources to ensure ongoing compliance with applicable data privacy and cybersecurity laws. Claims that we have violated individuals’ privacy rights or breached our contractual obligations or policies, even if we are not found liable, could be expensive and time-consuming to defend, and could result in adverse publicity that could harm our business. Moreover, even if we take all necessary action to comply with legal and regulatory requirements, we could be subject to data breaches or other unauthorized access of personal information or other sensitive or confidential information, which could subject us to fines and penalties, as well as litigation and reputational damage and other adverse consequences. If we or our collaborators or our third-party service providers fail to keep apprised of and comply with applicable international, federal, state, or local regulatory requirements, we could be subject to a range of regulatory actions that could affect our or any collaborators’ ability to seek to commercialize our product candidates. Any threatened or actual governmental enforcement action or litigation where private rights of action are available could also generate adverse publicity, damage our reputation, result in liabilities, fines, and loss of business, and require that we devote substantial resources that could otherwise be used in other aspects of our business. With laws, rules, regulations, and other obligations relating to data privacy and cybersecurity imposing new and relatively burdensome obligations, and with the substantial uncertainty over the interpretation and application of these and other obligations, we may face challenges in addressing their requirements and making necessary changes to our policies and practices and may incur significant costs and expenses in an effort to do so. We are currently in the process of developing and updating our policies and procedures in accordance with requirements under applicable data privacy and cybersecurity laws, rules and regulations and have not completed formal assessments of whether we are in compliance with all applicable data privacy and cybersecurity laws, rules and regulations. Additionally, if third parties with which we work, such as our collaborators, vendors or other third-party service providers, violate applicable laws, rules or regulations or our policies, such violations may also put our or our clinical trial and employee data, including personal or other sensitive or confidential information, at risk, and our business, financial condition, results of operations, and prospects may be adversely affected. We are subject to certain U.S. and foreign export and import controls, sanctions, embargoes, anti-corruption laws, and anti-money laundering laws and regulations. Compliance with these legal standards could impair our ability to compete in domestic and international markets. We can face criminal liability and other serious consequences for violations, which can harm our business. We are subject to export control and import laws and regulations, including the U.S. Export Administration Regulations, U.S. Customs regulations, various economic and trade sanctions regulations administered by the U.S. Treasury Department’s Office of Foreign Assets Controls, the U.S. Foreign Corrupt Practices Act of 1977, as amended, or FCPA, the U.S. domestic bribery statute contained in 18 U.S.C. § 201, the U.S. Travel Act, the USA PATRIOT Act, and other state and national anti-bribery and anti-money laundering laws in the 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 expect to have direct or indirect interactions with officials and employees of government agencies or government-affiliated hospitals, universities, and other organizations, and we expect our international activities to increase in time. We may engage third parties to conduct clinical trials, obtain necessary permits, licenses, patent registrations and other regulatory approvals or sell our products outside the United States, to conduct clinical trials, and/or to obtain necessary permits, licenses, patent registrations, and other regulatory approvals. 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 such activities. Any violations of the laws and regulations described above may result in substantial civil and criminal fines and penalties, imprisonment, the loss of 69 export or import privileges, debarment, tax reassessments, breach of contract and fraud litigation, reputational harm, and other consequences. If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have a material adverse effect on 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, including radioactive materials and gas. Our operations involve the use of hazardous and flammable materials, including chemicals and biological and radioactive materials. Our operations also produce hazardous waste products. We generally contract with third parties for the disposal of these materials and wastes. We cannot eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from our use of hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties. Our use of facilities that use and produce radioactive materials subjects us to compliance with decommissioning and decontamination, or D&D, requirements when we close those facilities, exposing us to potentially significant costs. Our product candidates are manufactured using radioactive components, such as the radioisotope 225 Ac. When one of such facilities reaches the end of its useful life or if we need to abandon such facility for any other reason, we are obligated under the laws and regulatory rules of the various jurisdictions in which we operate to decommission and decontaminate such facility. We have no experience with D&D, and the costs of such D&D may be substantial. Estimating the amount and timing of such future D&D costs includes, among other factors, country-specific requirements and projections as to when a facility will retire or the useful life of a facility. If we do not conduct D&D properly at any of our sites, we may suffer significant additional costs to remediate any D&D deficiencies, fines, regulatory or criminal charges or other sanction or legal action, any of which could have a material adverse effect upon our business, financial condition and results of operations. Although we have estimated our future D&D costs and recorded a liability for such costs, there can be no assurances that we will not incur material D&D costs beyond such estimates or our provisions. 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, and this insurance may not provide adequate coverage against potential liabilities. We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous, or radioactive materials. In addition, we may incur substantial costs to comply with current or future environmental, health and safety laws and regulations. Current or future environmental laws and regulations may impair our research, development, and production efforts, which could harm our business, financial condition, results of operations or prospects. Risks related to manufacturing We intend to build and operate our own manufacturing facility for preclinical and clinical supply needs, which will require significant resources, and we may fail to successfully establish and operate our facility, which could adversely affect our clinical trials and the commercial viability of our product candidates. We are currently establishing and building a manufacturing facility, in addition to our reliance on CDMOs for the manufacture of our product candidates for preclinical and clinical needs. We expect that construction of our own manufacturing facility will provide us with enhanced control of material supply for preclinical studies and clinical trials, enable the more rapid implementation of process changes, and allow for better long-term cost efficiencies. However, we have no experience as a company in construction of a manufacturing facility and may never be successful in building our own manufacturing facility or capability. As a result, we will also need to hire additional personnel to manage our operations and facilities and develop the necessary infrastructure to continue the research and development and manufacture of our product candidates. We, as a company, have no experience in setting up, building, or eventually managing a manufacturing facility. If we fail to complete the planned construction and buildout in an efficient manner, or fail to recruit the required personnel and generally manage our growth effectively, the development and production of our product candidates could be curtailed or delayed. Even if we are successful, our manufacturing capabilities could be affected by cost-overruns, unexpected delays, equipment failures, labor shortages, natural disasters, power failures and numerous other factors that could prevent us from realizing the intended benefits of our manufacturing strategy and have a material adverse effect on our business. Furthermore, if we are successful in building our own manufacturing facility, we will continue to be reliant on our CDMOs for clinical and commercial supply, if our product are approved, and their continued compliance with relevant regulations. In addition, the FDA, the EMA, and other foreign regulatory authorities may require us to submit samples of any lot of any approved product together with the protocols showing the results of applicable tests at any time. Under some circumstances, the FDA, the EMA, or other foreign regulatory authorities may require that we not distribute a lot until the relevant agency authorizes its release. Slight deviations in the manufacturing process, including those affecting quality attributes and stability, may result in unacceptable changes in the product that could result in lot failures or product recalls. Lot failures or product recalls could cause us to delay product launches or clinical trials, which could be costly to us and otherwise harm our business, financial condition, results 70 of operations, and prospects. Problems in our manufacturing process could restrict our ability to meet clinical and market demand for our products. Any problems in our manufacturing process or facilities could make us a less attractive collaborator for potential partners, including larger pharmaceutical companies and academic research institutions, which could limit our access to additional attractive development programs. Our product candidates are biologics and the manufacture of our product candidates is complex. Even after our planned manufacturing facility is operating, we will continue to rely on third parties to manufacture our product candidates. Our business could be harmed if those third parties fail to provide us with sufficient quantities of product supplies or product candidates, or fail to do so at acceptable quality levels or prices. Our product candidates are biologics and the process of manufacturing them is complex, highly regulated and subject to multiple risks. As a result of these complexities, the cost to manufacture biologics is generally higher than traditional small molecule chemical compounds, and the manufacturing process for biologics is less reliable and is more difficult to reproduce. In addition, manufacturing our product candidates will require many reagents, which are substances used in our manufacturing processes to bring about chemical or biological reactions, and other specialty materials and equipment, some of which are manufactured or supplied by small companies with limited resources and experience to support commercial biologics production. Even minor deviations from normal manufacturing processes could result in reduced production yields, product defects, and other supply disruptions. If microbial, viral or other contaminations are discovered in our product candidates or in the manufacturing facilities in which our product candidates are made, such manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination. We have experienced manufacturing deviations and similar issues in the past, and may experience similar issues in the future. We cannot assure you that any stability failures or other issues relating to the manufacture of our product candidates will not occur in the future. Any such issues could cause delays in our development plans. Further, as product candidates are developed through preclinical to late-stage clinical trials towards approval and commercialization, it is common that various aspects of the development program, such as manufacturing methods, are altered along the way in an effort to optimize processes and results. Such changes carry the risk that they will not achieve these intended objectives, and any of these changes could cause our product candidates to perform differently and affect the results of planned clinical trials or other future clinical trials. Even if we are able to complete our manufacturing facility, we will continue to rely on U.S.-based third-party manufacturers or third-party collaborators for the manufacture of our product candidates and for commercial supply of any of our product candidates for which we or any of our potential future collaborators obtain marketing approval. We may be unable to maintain agreements with our existing third-party manufacturers, or to establish additional agreements with third-party manufacturers or to do so on acceptable terms. Even if we are able to establish agreements with third-party manufacturers, reliance on third-party manufacturers entails additional risks, including: • the number of potential manufacturers is limited and any new manufacturers are subject to the FDA’s review and approval of a supplemental BLA. This approval would require new testing and may require pre-approval inspections of the new manufacturer by the FDA. In addition, a new manufacturer would have to be educated in, or develop substantially equivalent processes for, production of our products; • our current third-party manufacturers are located in United States and we may encounter issues with exporting our product candidates into foreign jurisdictions; • our third-party manufacturers might be unable to timely manufacture our product or produce the quantity and quality required to meet our clinical and commercial needs, if any; • our third-party manufacturers may not be able to execute our manufacturing procedures and other logistical support requirements appropriately; • our third-party manufacturers may not perform as agreed, according to our schedule or specifications, or at all, may not devote sufficient resources to our product candidates, may give greater priority to the supply of other products over our product candidates, or may not remain in the contract manufacturing business for the time required to supply our clinical trials or to successfully produce, store, and distribute our products; • our third-party manufacturers are subject to ongoing periodic unannounced inspection by the FDA and corresponding state agencies to ensure strict compliance with GMPs and other government regulations and corresponding foreign standards. We do not have control over third-party manufacturers’ compliance with these and/or any other applicable regulations and standards; 71 • we may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our products; • our third-party manufacturers could breach, terminate or not renew their agreement with us at a time that is costly or inconvenient for us; • clinical and, if approved, commercial supplies for the raw materials and components used to manufacture and process our product candidates, particularly those for which we have no other source or supplier, may not be available or may not be suitable or acceptable for use due to material or component defects; • the possible mislabeling of clinical supplies, potentially resulting in the wrong dose amounts being supplied or active product or placebo not being properly identified; • the possible misappropriation of our proprietary information, including our trade secrets and know-how; • the possibility of clinical supplies not being delivered to clinical sites on time, leading to clinical trial interruptions, or of product supplies not being distributed to commercial vendors in a timely manner, resulting in lost sales; and • our third-party manufacturers may have unacceptable or inconsistent product quality success rates and yields. Our third-party manufacturers and clinical reagent suppliers may be subject to regulatory requirements or sanctions, as well as damage or interruption from, among other things, fire, natural or man-made disaster, power loss, telecommunications failure, unauthorized entry, computer viruses, denial-of-service attacks, acts of terrorism, human error, vandalism or sabotage, financial insolvency, bankruptcy and similar events. We currently engage WuXi Biologics (Hong Kong) Limited, or WuXi, with respect to the manufacture of miniprotein variants and recombinant production and pharmacokinetic studies unrelated to [ 225 Ac]Ac-AKY-1189 and [ 225 Ac]Ac-AKY-2519. Certain Chinese biotechnology companies and CMOs, including WuXi, may in the future become subject to 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, thereby potentially disrupting the supply of material to us. The recently proposed BIOSECURE Act would have banned U.S. government contracts, grants, and loans from being used towards biotechnology equipment and services produced or provided by certain named Chinese biotechnology companies, including WuXi, and would authorize the U.S. government to name additional Chinese biotechnology companies of concern. The legislation did not pass the U.S. Congress in 2024; however, on December 18, 2025, the BIOSECURE Act was passed as part of the final Fiscal Year 2026 National Defense Authorization Act. Although the newly passed act does not explicitly name WuXi, or any other companies in the statute, the BIOSECURE Act bans federal procurement or funding associated with “biotechnology companies of concern” and restricting use of their equipment and services in federal contracts, grants, and loans. The implementation of the act will be phased in over a period of years, and could severely restrict the ability of companies to work with certain Chinese biotechnology companies of concern without losing the ability to contract with, or otherwise receive funding from, the U.S. government. The new administration has substantially altered prior U.S. government international trade policy and has commenced activities to renegotiate, or potentially terminate, certain existing bilateral or multi-lateral trade agreements and treaties with foreign countries. In addition, the new administration has initiated or is considering imposing tariffs on certain foreign goods. Related to this action, certain foreign governments, including China, have instituted or are considering imposing tariffs on certain U.S. goods. It remains unclear what the new policies by the U.S government or foreign governments will or will not do with respect to tariffs or other international trade agreements and policies. A trade war or other governmental action related to tariffs or international trade agreements or policies has the potential to disrupt our research activities, affect our suppliers, increase the cost of materials purchased to manufacture our products, impact our ability to sell our products outside the U.S. or to sell our products outside the U.S. at competitive prices and/or to affect the U.S. or global economy or certain sectors thereof and, thus, could adversely impact our business. If the third parties we engage to supply materials or manufacture product candidates or products for preclinical testing or clinical or commercial supply should cease to do so for any reason, we would likely experience delays in advancing these preclinical tests and clinical trials and/or interruptions in commercial supply while we identify and qualify replacement suppliers or manufacturers, and we may be unable to obtain replacement supplies on terms that are favorable to us, or at all. If we are not able to obtain adequate supplies of our product candidates or products or the substances used to manufacture them, it could materially and adversely impact our business, prospects, operating results or financial condition. Each of these risks could delay or prevent the completion of our ongoing and future clinical trials or the approval of any of our product candidates by the FDA, result in higher costs or adversely impact commercialization of our product candidates. Any shortages in the supply of such raw materials used in the manufacture of our product candidates could delay or prevent the completion of our clinical trials or the approval of any of our product candidates by the FDA, result in higher costs or adversely impact commercialization of our product candidates. In addition, we may rely on third parties to perform certain specification tests on our product candidates prior to delivery to patients. If these tests are not appropriately done and test data are not reliable, patients could be put at risk of serious harm and the FDA could place significant restrictions on our company until deficiencies are remedied. 72 The facilities used by our contract manufacturers to manufacture our product candidates may be subject to inspections that will be conducted after we submit our BLA to the FDA. 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. Any product candidates that we may develop may compete with product candidates of other companies for access to manufacturing facilities. There are a limited number of manufacturers that operate under cGMP regulations and that might be capable of manufacturing for us. 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 approvals, license revocation, seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our products and harm our business and results of operations. Our contract manufacturers’ failure to achieve and maintain high manufacturing standards, in accordance with applicable regulatory requirements, or the incidence of manufacturing errors, could result in patient injury or death, product shortages, product recalls or withdrawals, delays or failures in product testing or delivery, cost overruns or other problems that could seriously harm our business. Contract manufacturers often encounter difficulties involving production yields, quality control and quality assurance, as well as shortages of qualified personnel. We may be unable to obtain a sufficient supply of 225 Ac or other radioisotopes to support clinical development or manufacturing at commercial scale. 225 Ac is a key component of [ 225 Ac]Ac-AKY-1189 and [ 225 Ac]Ac-AKY-2519 and, as a radiopharmaceutical company, we expect our future product candidates to include 225 Ac or other isotopes. Although we believe our present suppliers have adequate quantities of 225 Ac and labeling isotopes available to meet our current needs, we may encounter supply shortages which could affect our business operations and results of operations. There can be no assurance that our suppliers will renew the contracts on acceptable terms, or at all. Further, long-term suppliers are not yet producing beyond minimal research quantities and there is no guarantee they will come online in the time frame we expect. Even when a contract exists, we have very limited recourse under our current supply contracts if a supplier is unable to meet its obligations. Suppliers may be unable to meet their obligations for a number of reasons, for example, the U.S. Department of Energy has reserved its ability to cancel private orders when the supply is instead needed for national defense, environmental safety or there is a lack of capacity, and the likelihood of any such c