10-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K

(Mark One)

For the fiscal year ended December 31, 2024

Commission File Number 001-40335

Biomea Fusion, Inc.

(Exact name of Registrant as specified in its Charter)

900 Middlefield Road, 4th Floor Redwood City, California 94063

(Address of principal executive offices) (Zip Code)

Registrant’s telephone number, including area code: (650) 980-9099

Securities registered pursuant to Section 12(b) of the Act:

Title of each class TradingSymbol(s) Name of each exchange on which registered

Common Stock, $0.0001 par value BMEA The Nasdaq Global Select Market

Securities registered pursuant to Section 12(g) of the Act: None

Indicate by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒

Indicate by check mark if the Registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. Yes ☐ No ☒

Indicate by check mark whether the Registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐

Indicate by check mark whether the Registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the Registrant was required to submit such files). Yes ☒ No ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

Large accelerated filer ☐ Accelerated filer ☐

Non-accelerated filer ☒ Smaller reporting company ☒

Emerging growth company ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit 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 aggregate market value of the voting equity held by non-affiliates of the Registrant, based on the closing price of the shares of common stock on the Nasdaq Global Select Market on June 30, 2024, was $124,145,240.

The number of shares of Registrant’s Common Stock outstanding as of March 24, 2025 was 37,572,250.

DOCUMENTS INCORPORATED BY REFERENCE

Portions of the Registrant’s definitive proxy statement to be filed with the Securities and Exchange Commission, or SEC, on or before the date 120 days after the conclusion of the Registrant’s fiscal year ended December 31, 2024 pursuant to Regulation 14A in connection with the Registrant’s 2025 Annual Meeting of Stockholders are incorporated by reference into Part III of this Annual Report on Form 10-K.

Table of Contents

Page

PART I

Item 1. Business 5

Item 1A. Risk Factors 36

Item 1B. Unresolved Staff Comments 93

Item 1C. Cybersecurity 93

Item 2. Properties 94

Item 3. Legal Proceedings 94

Item 4. Mine Safety Disclosures 94

PART II

Item 6. Selected Financial Data 95

Item 7A. Quantitative and Qualitative Disclosures About Market Risk 103

Item 8. Financial Statements and Supplementary Data 103

Item 9A. Controls and Procedures 128

Item 9B. Other Information 129

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 129

PART III

Item 10. Directors, Executive Officers and Corporate Governance 130

Item 11. Executive Compensation 130

Item 14. Principal Accountant Fees and Services 130

PART IV

Item 15. Exhibits, Financial Statement Schedules 131

Special Note Regarding Forward Looking Statements

This Annual Report on Form 10-K contains forward-looking statements about us and our industry that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this Annual Report on Form 10-K, including statements regarding our strategy, future financial condition, future operations, projected costs, prospects, plans, objectives of management and expected market growth, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. These forward-looking statements include, but are not limited to, statements about:

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our financial performance;

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the sufficiency of our existing cash, cash equivalents and restricted cash to fund our future operating expenses and capital expenditure requirements;

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our estimates regarding expenses, future revenue, capital requirements and needs for additional financing;

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our anticipated use of our existing cash, cash equivalents and restricted cash;

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the implementation of our strategic plans for our business and product candidates;

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the size of the market opportunity for our product candidates and our ability to maximize those opportunities;

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the initiation, timing, progress and results of our research and development programs, preclinical studies, clinical trials and investigational new drug applications ("IND") and other regulatory submissions;

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the beneficial characteristics, safety, efficacy and therapeutic effects of our product candidates and the ability of our FUSIONTM System to generate additional product candidates with such characteristics;

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the timing, progress and focus of our ongoing and future clinical trials, and the reporting of data from those trials;

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the ability of our clinical trials to demonstrate safety and efficacy of our product candidates, and other favorable results;

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our plans relating to the clinical development of our product candidates, including the disease areas to be evaluated;

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our ability to obtain and maintain regulatory approval of our product candidates;

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our plans relating to commercializing our product candidates, if approved;

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our estimates of the patient populations addressable by our product candidates, if approved, and the number of participants that will enroll in our ongoing and planned clinical trials;

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the expected benefits of potential future strategic collaborations with third parties and our ability to attract collaborators with development, regulatory and commercialization expertise;

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the success of competing therapies that are or may become available;

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the timing or likelihood of regulatory filings and approvals, including our expectation to seek special designations, such as orphan drug designation, for our product candidates;

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our plans relating to the further development and manufacturing of our product candidates, including for additional indications that we may pursue;

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existing regulations and regulatory developments in the United States and other jurisdictions;

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our plans and ability to obtain or protect intellectual property rights, including extensions of existing patent terms where available;

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our plan to rely on third parties to conduct and support preclinical and clinical development;

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our ability to retain the continued service of our key personnel and to identify, hire and then retain additional qualified personnel;

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the impact of any global health emergencies or other related disruptions on our business;

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unfavorable macroeconomic conditions or market volatility resulting from global economic conditions or geopolitical developments, including supply chain issues, inflationary pressures, market volatility, international tariffs, trade protection measures, economic sanctions, economic slowdowns or recessions, acts of war, and civil and political unrest; and

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our expectations regarding the period during which we will qualify as an emerging growth company under the Jumpstart Our Business Startups Act of 2012, as amended.

We have based these forward-looking statements largely on our current expectations, estimates, forecasts and projections about future events and financial trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. Although we believe that we have a reasonable basis for each forward-looking statement contained in this Annual Report on Form 10-K, we cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur at all. You should refer to the section titled “Risk Factors” for a discussion of important factors that may cause our actual results to differ materially from those expressed or implied by our forward-looking statements. Furthermore, if our forward-looking statements prove to be inaccurate, the inaccuracy may be material. Except as required by law, we undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise. We qualify all of the forward-looking statements in this Annual Report on Form 10-K by these cautionary statements.

Summary Risk Factors

The following is a summary of the principal factors that make an investment in our common stock speculative or risky. This summary does not address every aspect of our risk factors, all of the risks that we face, or other factors not presently known to us or that we currently believe are immaterial. Additional discussion of the risks summarized in these summary risk factors, and other risks that we face, can be found under the heading “Risk Factors” in this Annual Report on Form 10-K and should be carefully considered, together with other information in this Annual Report on Form 10-K and our other filings with the U.S. Securities and Exchange Commission (SEC), before making investment decisions regarding our common stock.

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We have a limited operating history, limited experience in conducting clinical trials, have not completed the clinical development of any product candidates, have no products approved for commercial sale, and have not generated any revenue, which may make it difficult for you to evaluate our current business and likelihood of success and viability.

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We will require substantial additional capital to finance our operations. If we are unable to raise such capital when needed, or on acceptable terms, we may be forced to delay, reduce and/or eliminate one or more of our research and product development programs or future commercialization efforts.

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Our discovery and development activities are focused on the development of novel covalent small-molecule therapies to treat patients with diabetes and obesity, and the approach we are taking to discover and develop such product candidates is novel, may never lead to marketable products and may not ultimately represent a significant or viable market.

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Our novel approach to the discovery and development of our current and future product candidates is unproven, and we may not be successful in our efforts to use and expand our FUSIONTM System to build a pipeline of product candidates with commercial value.

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We are early in our development efforts and are substantially dependent on our product candidates, icovamenib (formerly BMF-219) and BMF-500. If we are unable to advance icovamenib, BMF-500 or any of our future product candidates through clinical development, obtain regulatory approval and ultimately commercialize icovamenib, BMF-500 or any of our future product candidates, or experience significant delays in doing so, our business, financial condition and results of operations will be materially adversely affected.

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Preclinical and clinical drug development is a lengthy and expensive process, with an uncertain outcome. Our preclinical and clinical programs may experience delays or may never be initiated or completed, which would adversely affect our ability to obtain regulatory approvals or commercialize our product candidates on a timely basis or at all, which could have an adverse effect on our business.

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The results of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and the results of our clinical trials may not satisfy the requirements of the U.S. Food and Drug Administration (FDA) or other

comparable foreign regulatory authorities. Successful preclinical studies and clinical trials cannot provide assurance of successful commercialization.

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We have limited experience as a company in conducting clinical trials and have not successfully completed the clinical development of any product candidates to date.

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Adverse global economic conditions, including supply chain issues and inflationary pressures, could materially adversely impact our business, results of operations, and financial condition, including our preclinical studies and clinical trials.

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The regulatory approval processes of the FDA and other comparable foreign regulatory authorities are lengthy, time consuming and inherently unpredictable. If we are not able to obtain, or if there are delays in obtaining, required regulatory approvals for our product candidates, we will not be able to commercialize, or will be delayed in commercializing, our product candidates, and our ability to generate revenue will be materially impaired.

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The price of our stock may be volatile, and you may not be able to resell shares of our common stock at or above the price you paid.

PART I

Item 1. Business

Overview

We are a clinical-stage diabetes and obesity medicines company focused on the discovery and development of oral covalent small molecule drugs to treat patients with metabolic diseases. We aim to cure.

A covalent small molecule drug is a synthetic compound that forms a permanent bond to its target protein and offers potential advantages over conventional non-covalent drugs, including greater target selectivity, lower systemic drug exposure, and the ability to drive a deeper, more durable response. Leveraging our extensive expertise in covalent chemistry and development, we built our proprietary FUSIONTM System discovery platform to advance a pipeline of novel small molecule product candidates. Our lead clinical program’s drug candidate, icovamenib, is currently being developed as an orally bioavailable, and selective covalent inhibitor of menin in two clinical and multiple preclinical studies, investigating icovamenib’s potential in type 1 and type 2 diabetes, as well as its impact in obesity.

After working closely together at Pharmacyclics, Inc. (formerly Nasdaq: PCYC) (Pharmacyclics), our former Chief Executive Officer, Thomas Butler, and Chief Operating Officer and President, Ramses Erdtmann, founded Biomea Fusion, Inc. (the Company, we, our, or us) in 2017 with the shared vision and goal of developing targeted therapies for patients. Today, we have grown to approximately 80 employees, and has built a management team with significant experience both in precision medicine and in progressing drug candidates from early-stage research to clinical trials and ultimately to regulatory approval and commercialization. We have cultivated in-house expertise in medicinal chemistry, biology, translational medicine, computational biology, and chemistry, in vitro and in vivo pharmacology, biomarker development, and manufacturing. We have also established internal expertise and synergies in clinical development, clinical operations, pharmacovigilance, clinical pharmacology, regulatory affairs, and quality control. Members of the team have held various positions at several renowned biotechnology companies including Gilead Sciences, Inc. (Nasdaq: GILD), Genentech, Inc., Pharmacyclics, AbbVie Inc. (NYSE: ABBV), Celera Genomics, Johnson and Johnson, Inc. (NYSE: JNJ), and others. The team includes the co-inventors of the covalent inhibitors Imbruvica, Remdesivir, and Harvoni. We are supported by our experienced Board, broad scientific advisory board of renowned experts in diabetes and obesity, and a leading syndicate of investors.

Management Update

In March 2025, the Company announced a leadership transition, appointing Board member Mick Hitchcock, Ph.D., as Interim Chief Executive Officer, succeeding Thomas Butler. Dr. Michael J. M. Hitchcock, Ph.D. (Mick) has served as a member of the Company’s board since March 2021. Dr. Hitchcock is currently a Past Chair of the University of Nevada, Reno (UNR) Foundation and Adjunct Professor of Microbiology at UNR Medical School, a position in which he has served since July 2016. Dr. Hitchcock’s career in pharmaceutical research and development initially began with Bristol-Myers Squibb, where he served in several infectious disease research and project planning roles from 1980 through 1993. He joined Gilead Sciences, Inc. in 1993 and during his 27 years with the Company, he held a variety of positions, including vice president roles with responsibility for project and portfolio management, alliance management, strategic planning, medical affairs and specific areas of research. He also served as Senior Advisor at Gilead from 2009 through November 2019. During his career, he was involved in the development and commercialization of a number of anti-infective agents, primarily antivirals for treatment of HIV, HBV, influenza, CMV and other viral diseases. Dr. Hitchcock holds a Ph.D. in microbiology from the University of Melbourne, Australia and B.Sc. and M.Sc. degrees in biochemistry from the University of Manchester Institute of Science and Technology, England. He also conducted post-doctoral research at Georgetown University and NIH prior to joining industry.

OUR PROGRAMS

Our current pipeline and potentially addressable patient population

Icovamenib

Our lead product candidate, icovamenib, is designed to be an orally bioavailable, potent, and selective covalent inhibitor of menin, a ubiquitously expressed scaffold protein that functions in histone modification and epigenetic gene regulation to impact multiple cellular processes including cell cycle control, apoptosis, and DNA damage repair. Menin plays a key role in beta cell proliferation and function, as previously demonstrated through increased beta cell mass generation in Men1 knockout mice (Ja et al., 2021). We are developing icovamenib for the treatment of menin regulated or dependent diseases such as type 1 and type 2 diabetes.

Dual Potential Mechanism of Action

Icovamenib has demonstrated a generally well-tolerated safety profile in preclinical and early-stage clinical studies. Mechanistic studies support two potential modes of action: (i) increasing beta cell mass and function, thereby enhancing insulin synthesis and secretion, and (ii) upregulating glucagon-like peptide-1 (GLP-1) receptor expression, which may contribute to improved glycemic control and metabolic benefits.

(i)

Beta Cell Quantity and Function

Icovamenib is designed to increase beta cell mass and function, addressing a fundamental deficiency in patients with diabetes. Through its proposed mechanism of action, icovamenib has been observed in non-clinical and early-stage clinical studies to promote glucose-regulated beta cell proliferation and enhance insulin synthesis and secretion. By inducing controlled beta cell regeneration, this approach aims to restore endogenous insulin production and provide a durable glycemic benefit.

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GLP-1 Receptor Expression

In addition to its effects on beta cell mass and function, icovamenib has been shown to upregulate GLP-1 receptor expression in preclinical studies, which may enhance incretin signaling and improve glucose metabolism. Non-clinical data suggest that this upregulation could contribute to metabolic benefits, including improved glycemic control and potential weight loss.

Due to the long half-life of beta cells, icovamenib is not intended as a chronic therapy for insulin deficient diabetes, but rather as a 12-week treatment designed to produce lasting effects beyond the period of active administration.

We are currently investigating icovamenib in diabetes in our ongoing Phase II clinical trial COVALENT-111, for patients with type 2 diabetes, and our ongoing Phase II clinical trial COVALENT-112, for patients with type 1 diabetes. Loss of functional beta cell mass is a core component of the natural history in both types of diabetes – type 1 diabetes, which is mediated by autoimmune dysfunction leading to destruction of the beta cells, and type 2 diabetes, which is mediated by metabolic dysfunction. Beta cells are found in the pancreas and are responsible for the synthesis and secretion of insulin, a hormone that helps regulate the body’s capacity to absorb, metabolize, and convert glucose for energy. In patients with diabetes, the beta cell mass and function are diminished over time, leading to insufficient insulin secretion and hyperglycemia. Menin is thought to act as a brake on beta cell turnover / beta cell growth, supporting the notion that controlled inhibition of menin could lead to replenishment of normal healthy beta cells. Based on these and other scientific findings, we are exploring the potential for menin inhibition as a possible therapeutic approach to improve beta cell health and mass, and thus potentially treat an underlying driver of diabetes.

We are also exploring the potential benefits icovamenib can provide to patients with diabetes or obesity who are either newly dosed with a glucagon-like peptide-1 receptor (GLP-1R)-based therapy or failing on a GLP-1R-based therapy. In non-clinical studies, icovamenib when dosed in combination with semaglutide showed an additional 11.5% body weight reduction and 43% increase in lean muscle mass compared to semaglutide alone in the Zucker Diabetic Fatty (ZDF) rat model. The combination with semaglutide approximately doubled C-peptide production per unit of glucose compared to semaglutide alone, leading to a 60% improved reduction of fasting blood glucose. In ex vivo human islet experiments icovamenib enhanced the activity of GLP-1R-based therapies, leading to a substantial increase in insulin secretion. In addition, topline data from the COVALENT-111 study showed that 12 weeks of daily icovamenib in patients uncontrolled on a GLP-1R-based therapy (n=10) led to a mean HbA1c reduction of 0.84% at week 26.

BMF-650

GLP-1 is a naturally occurring incretin hormone that plays a vital role in glucose homeostasis and appetite regulation. GLP-1 receptor agonists (GLP-1 RAs) are a class of medications that bind to and activate GLP-1 receptors, mimicking the effects of native GLP-1. These agents have demonstrated robust clinical efficacy in improving glycemic control, promoting weight loss, and enhancing insulin sensitivity in individuals with type 2 diabetes and obesity.

BMF-650, is an investigational next-generation, oral small-molecule GLP-1 RA, developed by our team. BMF-650 demonstrated positive early preclinical activity, including improved glucose-stimulated insulin secretion, reduction in blood glucose concentration, and appetite suppression in cynomolgus monkeys. Preclinical studies to evaluate the properties of BMF-650 in comparison to a leading oral GLP-1 RA showed that BMF-650 exhibited higher bioavailability and a less variable pharmacokinetic profile, which may translate to improved tolerability and support successful dose escalation in patients. In cynomolgus monkey studies, BMF-650 showed significant improvements in glucose-stimulated insulin secretion, in line with findings from human donor islet experiments. BMF-650 also demonstrated superior glucose control. Appetite suppression studies demonstrated that daily oral BMF-650 dosing significantly reduced food intake during peak drug concentration, with sustained effects throughout the day for a six-day study period. These findings highlight BMF-650’s potential as an oral treatment for diabetes and obesity. Our strategy with BMF-650 is centered on flat pharmacokinetics and an increase in area under the curve (AUC) to drive development of a potential best-in-class, oral, small molecule GLP-1.

BMF-650 is advancing through IND enabling studies. With its unique pharmacokinetic profile and enhanced bioavailability, we believe BMF-650 has the potential to provide a best-in-class therapeutic option for diabetes and obesity. Submission of the IND application for BMF-650 is planned for the second half of 2025.

RECENT DEVELOPMENT UPDATES

COVALENT-111 (Type 2 Diabetes)

COVALENT-111 is a multi-site, randomized, double-blind, placebo-controlled Phase I/II study evaluating icovamenib in healthy adults and adults with type 2 diabetes. In December 2024, we reported that the study successfully met its primary endpoint, demonstrating statistically significant reductions in HbA1c at Week 26 compared to placebo after only 12 weeks of dosing. Best response was achieved in beta cell deficient patients on one or more antidiabetic agents at baseline, showing a placebo-adjusted mean reduction of 1.47% in HbA1c at Week 26 with statistical significance, after only 12 weeks of dosing icovamenib with 100 mg once daily. Overall, icovamenib was generally well-tolerated, with no adverse-event related discontinuations, no hypoglycemic events and no study drug-related serious adverse events. The Expansion Phase (Phase IIb) of the study is ongoing, with final 52-week results anticipated in the second half of 2025.

COVALENT-112 (Type 1 Diabetes)

COVALENT-112 is a multi-site, randomized, double-blind, placebo-controlled Phase I/II study evaluating icovamenib in healthy adults and adults with type 1 diabetes. The study’s primary endpoint assesses the mean change from baseline in stimulated C-peptide AUC at Week 12. The former clinical hold imposed in June 2024 and lifted in September 2024, had a more profound impact on the COVALENT-112 study in type 1 diabetes, where over 90% of the targeted patient population was not able to complete dosing due to the clinical hold. We are therefore planning to continue enrollment in the COVALENT-112 study so that we can provide a more complete update in this patient population.

FDA Clinical Hold Resolution

In June 2024, the FDA imposed a clinical hold on the Phase I/II trials of icovamenib in type 1 and type 2 diabetes due to observations from the escalation phase, when higher dosages of icovamenib were tested. In September 2024, following submission to the FDA of an in-depth review of additional safety data showing that the concerning elevated lab values occurred at 200 mg and 400 mg starting doses, not at 100 mg or lower, and none of the elevated lab values translated to serious liver injury or impairment, and 30 days later, the FDA issued a full lift of the clinical hold. The expansion phase continued as planned at the 100 mg starting dose.

Expansion into Obesity Treatment

In October 2024, we advanced BMF-650, an investigational next-generation, oral small-molecule GLP-1 RA, for the treatment of diabetes and obesity. IND-enabling studies are ongoing, and submission of the IND application for BMF-650 is planned for the second half of 2025.

Oncology Programs Discontinuation

In January 2025, we announced our strategic decision to transition into a diabetes and obesity medicines company. Based on the most recent clinical trial results, the strategic focus for icovamenib will be in metabolic disorders. We plan to conclude our studies exploring icovamenib’s potential in oncology and explore partnerships to further advance our oncology assets (i.e. BMF-500), while concentrating internal resources on metabolic disorders. As part of this transition, we have discontinued our oncology programs, including COVALENT-101 (hematologic malignancies) and COVALENT-102 (solid tumors), and are concluding our study COVALENT-103 (BMF-500 for acute leukemia).

Our Strategy – We Aim to Cure

We are committed to pioneering innovative therapies that address the underlying causes of metabolic diseases, with a primary focus on diabetes and obesity. Our strategy is driven by a patient-centric approach, leveraging our expertise in covalent drug development and our proprietary FUSIONTM System to create novel, potential first-in-class therapies that provide durable clinical benefits in these disease settings.

Our strategy is to identify key cellular regulators of metabolic homeostasis and molecular drivers of diabetes and other metabolic diseases, then to design, optimize, and develop covalent inhibitors that have the potential to produce clinically differentiated therapeutic profiles with an aim to cure. We focus on restoring beta cell function and improving glucose metabolism through precise targeting of the key pathways involved in diabetes progression. We seek to recognize the clinical value of precision targeting of malfunctioning proteins through optimized covalent inhibition.

Guided by the FUSIONTMsystem, we design covalent small molecule drug candidates to work in a two-step process. First, an inhibitor reversibly associates with the target protein, bringing its chemical warhead in proximity to a reactive amino acid residue of the target protein. In the second step, a permanent covalent bond is formed between the inhibitor and the target protein. Conventional reversible inhibitors differ from covalent inhibitors in that they do not involve the second step. The covalent “lock-and-key”, when optimized, can result in small molecule candidates with high selectivity for their targets, limited off-target activity, potentially generating a large therapeutic window. The only way then for the disease-driving functional protein to return is through de novo synthesis. This allows the drug candidate to potentially be dosed in short bursts without requiring constant systemic drug exposure as may be required by more conventional reversible drug candidates. In addition, conventional reversible small molecule drug candidates may bind to multiple targets, which can lead to poor selectivity and cause unintended side effects. We believe the covalent approach affords an added degree of selectivity, since “innocent” targets are not exposed to the drug for any longer than necessary.

Key Strategic Priorities

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Advance Icovamenib as a Disease-Modifying Therapy for Diabetes and Obesity:

Icovamenib, a potentially first-in-class covalent menin inhibitor, has demonstrated the potential to restore beta cell function, and mass to improve glycemic control. We are prioritizing the development of icovamenib initially for two key patient populations:

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Severe Insulin Deficient Diabetes Patients (SIDD): Representing approximately 14 million of type 2 diabetes in the United States and European Union (EU), and more than 50 million patients in Asian countries. This population of patients exhibit the highest unmet medical need, experiencing high treatment failure rates, rapid progression to insulin-dependency, and poor cardiovascular outcomes.

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Combination with GLP-1R Based Therapies: Icovamenib has been shown to enhance the activity of GLP-1 Rs in preclinical studies, leading to superior glucose control, weight loss, and muscle preservation. We plan to initiate a late-stage clinical trial evaluating icovamenib as an adjunct to GLP-1R-based therapies in subjects who remain uncontrolled or who are newly treated with a GLP-1R-based therapy.

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Expand the Metabolic Pipeline with BMF-650: BMF-650, our next-generation oral GLP-1 RA, is advancing through IND-enabling studies. With its unique pharmacokinetic profile and enhanced bioavailability, BMF-650 has the potential to provide a best-in-class therapeutic option for diabetes and obesity. Submission of the IND application for BMF-650 is planned for the second half of 2025.

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Evaluate Opportunities to Enhance the Potential of our Programs in Collaboration with Third Parties. We own full worldwide development and commercialization rights to each of our programs. In the future, we may selectively enter into collaborations where we believe there is an opportunity to speed up clinical development or enhance the commercialization potential of our product candidates. We intend to commercialize our product candidates in key markets either alone or with partners in order to maximize the worldwide commercial potential of our programs.

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Maintain our Entrepreneurial Outlook, Scientifically Rigorous Approach, and Culture of Tireless Commitment to Patients. We will continue to apply transformative science in the development of novel targeted therapies for patients suffering from metabolic diseases with limited therapeutic options. We intend to continue building our team of qualified individuals who share our commitment to collaboration and scientific rigor in the development of novel covalent product candidates that may have the potential to treat patients with metabolic diseases.

Background on Covalent Inhibition

A covalent small molecule drug is a synthetic compound that forms a permanent bond to its target protein through a combination of non-covalent and covalent interactions and can either stimulate or inhibit target protein function. Reversible drugs, which make up the majority of approved drugs, exert their action by establishing an equilibrium between free drug, target protein, and drug-target complex. Therefore, a reversible inhibitor, by definition, can allow an inhibited drug-protein complex to convert back to free drug and active protein unless sufficient concentration of free drug is present in the local environment. This need for constant coverage typically requires continuous systemic exposure, which can pose safety and tolerability challenges.

Forming a covalent bond between a target protein and covalent drug can be described as a two-step process. First, the compound creates a reversible, non-covalent bond to the target protein that can enable a covalent bond by placing a reactive atom on the drug compound close to a complementary reactive atom on the target protein. The second step involves the formation of a specific and long-lived covalent bond between the complementary moieties, resulting in a complex that persists throughout the lifetime of the target protein and effectively permanently disables target protein function.

Key Advantages of Covalent Drugs

Since the discovery of aspirin in 1899, covalent drugs have shown the potential to offer a number of possible safety, tolerability, and efficacy advantages over conventional reversible drugs through multiple mechanisms.

Persistent site occupancy of a marketed, covalent inhibitor in the absence of sustained drug exposure

Beyond aspirin and the Bruton’s tyrosine kinase covalent inhibitor ibrutinib (marketed as IMBRUVICA® for various B-cell malignancies and chronic graft versus host disease), a number of other covalent inhibitors have been approved by the FDA, including sofosbuvir (marketed as SOVALDI® for hepatitis C virus), tenofovir (marketed as VIREAD® for hepatitis B virus), osimertinib (marketed as TAGRISSO® for NSCLC), and bortezomib (marketed as VELCADE® for multiple myeloma and mantle cell lymphoma).

Challenges in Developing Covalent Drugs

Despite the potential advantages of covalent drugs, the majority of approved drugs are reversible binders. The inherent challenges in creating covalent drugs present significant barriers to entry to discover and develop these molecules. The key challenges in developing covalent drugs include:

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Complexity. The discovery and development of covalent drugs requires significant structural knowledge and medicinal chemistry capabilities, including the ability to construct complex novel chemical scaffolds. In addition, not all disease-causing proteins have the properties necessary for the application of covalent binding. While advancements in structural knowledge of the proteome provides greater opportunity to identify potential targets for covalent binding, we believe the lack of specialized medicinal chemistry expertise needed to leverage this knowledge has impeded the development of covalent drugs. And lastly, not all covalent inhibitors are created equal.

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Safety and tolerability. While the covalent binding modality can provide a high degree of selectivity, poorly conceived molecules with promiscuous binding profiles can pose a risk of significant off-target interactions and safety concerns. Given this significant and long-standing challenge, without the structural biology and covalent binding chemistry expertise, drug developers have historically been discouraged from pursuing covalent binders.

We believe we are positioned to leverage the significant expertise, foundational knowledge, and capabilities that our management team first acquired while developing ibrutinib and that we have expanded and refined over the last three years to create our FUSIONTM System discovery platform.

FUSIONTM System Discovery Platform

We believe that covalent small molecules have the potential to address the key limitations of existing reversible therapeutics and treat diseases where targeted therapies are not yet approved. Leveraging our extensive experience developing covalent drugs and covalent binding chemistry expertise, we built our proprietary FUSIONTM System to enable the design and development of novel covalent small molecule product candidates against high-value drivers of disease. The system also has

the capability to create a novel non-covalent inhibitor, which we may advance depending on the target. We have described some of the differences between the FUSIONTM System and traditional small molecule drug discovery approaches below:

The FUSIONTMSystem leverages artificial intelligence (AI) and virtual reality (VR) matching and custom synthesis to develop novel drugs

Our FUSIONTM System Discovery platform encompasses the following:

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Target Selection Validation and AI/VR Matching: We use our expertise in structural biology and covalent binding chemistry to identify both validated and novel targets that we believe may have a demonstrable and specific impact on disease and have particular structural characteristics that would be amenable to direct intervention with a covalent binder.

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Custom Scaffold Creation: We create novel chemical scaffolds using a computational platform to exploit the unique structural elements of a specific target protein. We then screen these scaffolds with in-house technologies to select the optimal candidates for further construction and design. This evaluation process is intended to increase the probability of having multiple targeted compounds that can advance through the discovery process and into the clinic.

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Molecule Optimization/Refinement: Using our proprietary suite of computational technologies, assays, analytical approaches, chemistry, and know-how we strive to maximize the potential selectivity, potency, safety, and convenience of our oral, covalent small molecule product candidates. We avoid compound library screening, which results in highly selective/specified scaffolds. This saves considerable time during the lead optimization step.

We aim to leverage our capabilities and platform to establish ourselves as a leader in developing covalent small molecules in order to maximize the depth and durability of clinical benefit for patients with various metabolic diseases.

Our Initial Focus: Menin

Menin and Beta Cell Biology in Diabetes

Diabetes is a chronic metabolic disease that affects the body’s ability to regulate blood sugar levels, leading to elevated glucose in the bloodstream. Over time, uncontrolled blood sugar can result in serious complications, including cardiovascular disease, kidney failure, nerve damage, and vision impairment. People with diabetes often have a reduced life expectancy compared to those without this disease. Diabetes is also a significant economic burden on the U.S. health care system, ranking as the 7th leading cause of death in the U.S. and accounting for approximately one out of every four dollars spent on healthcare in the country. According to a study published in The Lancet, worldwide over 800 million adults are estimated to live with diabetes. The CDC estimates about two in five of the adult population in the U.S. are now expected to develop diabetes during their lifetime. More than 38.4 million people of all ages (about 11% of the U.S. population) have diabetes today, while an additional 97.6 million adults (more than one in three) have pre-diabetes, blood sugars that are higher than normal but not high enough to be classified as diabetes.

Despite the availability of numerous treatment options, there remains a critical need for improved therapies that can modify disease progression rather than simply managing symptoms. The American Diabetes Association (ADA) categorizes diabetes based on etiology and onset. Type 1 diabetes is caused by an autoimmune attack on pancreatic beta cells leading to absolute insulin deficiency, including latent autoimmune diabetes of adulthood. Type 2 diabetes is characterized by progressive beta cell dysfunction and insulin resistance. The primary treatment objective is to achieve glycemic control, typically measured by reductions in HbA1c (glycated hemoglobin), a marker indicating average blood glucose over the past two to three months, to 6.5% or lower. Effective glycemic control is critical in preventing or delaying complications such as kidney disease, heart disease and nerve damage.

The loss of functional beta cell mass is a fundamental driver of disease progression in both type 1 diabetes and type 2 diabetes. Beta cells, located in the pancreas, are responsible for producing and secreting insulin, a hormone essential for glucose metabolism and regulation. In diabetes, beta cell dysfunction and depletion lead to impaired insulin secretion, resulting in hyperglycemia. Researchers suggest that menin, a regulatory protein, plays a key role in beta cell proliferation. Inhibiting menin may remove this restriction, allowing for the regeneration and restoration of functional beta cells.

Diabetes progression of type 1 and type 2 driven by beta cell loss

Icovamenib – Clinical Development in Diabetes

We are prioritizing the development of icovamenib as a potential therapeutic candidate for metabolic diseases, including type 2 diabetes. Our development strategy is informed by positive topline data from the Phase II COVALENT-111 study and preclinical in-vivo data indicating a potential synergistic effect with GLP-1 RA-based therapies.

We are focusing our clinical development efforts initially on patients with severe insulin deficiency and patients currently receiving GLP-1 RA-based therapies to address the significant unmet medical need in these populations. Given its dual potential mechanism of action, which may include increasing beta cell mass and enhancing insulin synthesis, icovamenib is being evaluated as a potential disease-modifying treatment rather than a chronic therapeutic intervention. The Company remains committed to advancing its clinical program to assess icovamenib’s ability to provide sustained glycemic control and improve metabolic outcomes. We believe this innovative strategy has the potential to transform diabetes treatment by addressing the root causes of the disease rather than solely managing symptoms.

COVALENT-111 Type 2 Diabetes Phase II Study

COVALENT-111 is a multi-site, randomized, double-blind, placebo-controlled Phase I/II study. In the completed Phase I portion of the trial, healthy volunteers were enrolled in single ascending dose cohorts to evaluate safety at the prospective dosing levels for patients with type 2 diabetes. Phase II consists of multiple ascending dose cohorts and includes adult patients with type 2 diabetes uncontrolled by standard of care medicines. The dose escalation phase evaluated icovamenib at multiple dose levels with and without food. Patients were only dosed for four weeks and then followed up for 22 weeks while off treatment.

Following the Escalation Phase of COVALENT-111, the study advanced into an Expansion Phase (n>200) consisting of multiple cohorts dosing type 2 diabetes patients for longer dose durations. The first three arms (Arm A, B, and C) of the Expansion Phase are evaluating icovamenib dosed over eight and 12 weeks at 100 mg and 200 mg with up to 40 weeks of follow-up, off treatment.

The modified intent-to-treat population was defined as all randomized participants who took at least one dose of study drug (N=225) or placebo. The study was interrupted by the FDA imposed clinical hold, and therefore some patients could not complete their dosing period. The topline efficacy analysis provided in December 2024 focused on those patients who had completed at least 80% of their assigned dosing schedule prior to the clinical hold, the Per Protocol Patient population, and included a post-hoc analysis of the subgroup who were treated with one or more anti-hyperglycemic therapies at baseline (n=168). From those patients N=113 were on study drug and N=55 were on placebo. In total 10% of all patients enrolled were on no background therapy, 69% were on metformin alone, 16% were on two therapies and 5% were on three therapies.

In per protocol patients who were “uncontrolled” with at least one medication at baseline (N=115), icovamenib showed a statically significant, placebo-adjusted 0.36% reduction in HbA1c, independent of dose strength. The dose duration comparison analyzed all 113 patients, and those treated for eight weeks (N=45 Arm A) versus those treated for 12 weeks (N=69 Arm B and C) showed a difference in HbA1c reduction of 0.27% versus 0.42% respectively. The longer duration of treatment resulted in greater HbA1c lowering, with a placebo-corrected statistically significant higher reduction.

Each patient was classified into one of four identified phenotypes of type 2 diabetes based on their baseline characteristics prior to the readout. The various type 2 subtypes of diabetes are: Severe Insulin Deficient Diabetes (SIDD), Mild Obesity Diabetes (MOD), Mild Age Related Diabetes (MARD) and Severe Insulin Resistant Diabetes (SIRD). The statistical analysis plan prespecified each phenotype as well as the primary endpoint for analysis across each arm, prior to the recent readout of the Week 26 data. The identification of these subtypes was based on the specific algorithms specified by Ahlqvist E, et al. Lancet Diabetes Endocrinol. 2018;6:361-369. MOD and SIRD patients are generally considered insulin resistant and are identifiable by a higher BMI and higher homeostatic model assessment (HOMA) beta cell function (HOMA-β), indicating better beta cell functionality, versus MARD and SIDD patients who are generally considered insulin deficient with a lower BMI and a lower HOMA-β, indicating lower beta cell function. SIDD patients are known to present with the lowest c-peptide release and HOMA-β at baseline.

When comparing the per protocol patients who were considered “uncontrolled” (HbA1c >7.0%) in the various prespecified subtypes, COVALENT-111 study results after Week 26 showed that insulin deficient patients performed approximately six-fold better than those patients enrolled with insulin resistance. MOD and SIRD patients combined (N=69) showed a reduction in HbA1c of 0.13% versus the MARD and SIDD patients combined (N=44) who showed a combined reduction of 0.73% (statistically significant p=0.009), 14 weeks after completing treatment.

Comparing the various dosing arms (Arm A: dosing for eight weeks 100 mg once a day (QD)), Arm B: dosing for 12 weeks with 100 mg QD, Arm C: dosing for eight weeks with 100 mg QD and four weeks with 100 mg twice a day) the best performing Arm in the study was Arm B.

Reviewing the prespecified subtypes with insulin deficiency (MARD and SIDD patients) in these two study arms (Arm B and C, dosing at 12 weeks), they had a statistically significant 0.84% mean reduction in HbA1c. These results are further improved when reviewing the most insulin deficient patients, SIDD patients, who had a statistically significant mean reduction in HbA1c at Week 26 of 1.17% in both study arms (Arm B and C). Among only the Arm B patients, with just 12 weeks of dosing 100 mg QD, the most insulin deficient patients (SIDD patients) showed even further improved responses up to a statistically significant mean reduction in HbA1c at Week 26 of 1.47%. These data suggest that 12 weeks of dosing, particularly in insulin deficient patients, has the potential to result in a robust improvement in glycemic control at Week 26.

HbA1c Reduction Continued Over Time – Outside the Treatment Period

During the icovamenib 12-week treatment period, for both the combined 12-week arms (Arm B and C) and for Arm B alone, there were statistically significant reductions in HbA1c for all participants in those arms and greater improvements in HbA1c

in the insulin deficient patients. HbA1c levels reduced steadily, with a continued downward trajectory observed beyond Week 12. Notably, after the completion of treatment, during the off-treatment period, weeks 12 to 26, patients continued to experience reductions in HbA1c, suggesting a prolonged therapeutic effect.

This response profile supports icovamenib’s potential as a disease-modifying therapy for patients with insulin deficiency, with durable glycemic improvements even after treatment discontinuation.

The placebo-adjusted mean change in HbA1c was -0.75% at Week 12 (end of treatment period). Notably, the HbA1c reduction continued to improve post-treatment, reaching -1.47% at Week 26, which represents 14 weeks after treatment cessation.

These findings suggest that icovamenib may provide a durable glycemic benefit beyond the treatment period, supporting its potential role as a disease-modifying therapy in patients with severe insulin deficiency who have limited treatment options. Further clinical evaluation is ongoing to assess the long-term impact of icovamenib on glycemic control.

Icovamenib was generally well-tolerated. There were no study drug-related serious adverse events reported, no treatment discontinuations nor study discontinuation due to adverse events and there were no deaths in icovamenib- or placebo-treated patients.

In the COVALENT-111 study, in a post hoc analysis patients who were receiving GLP-1R based therapy at baseline exhibited a clinically meaningful 0.84% reduction in HbA1c following icovamenib administration across all dose levels. Notably, patients in Arm C achieved an even greater HbA1c reduction of 1.0%. These patients were considered “uncontrolled” at the time of enrollment (HbA1c > 7.0%) despite being on a GLP-1R based therapy. Additionally, they experienced up to 14% further reduction in body weight at Week 26.

We plan to initiate a late-stage development study evaluating icovamenib in SIDD subjects and a Phase II study evaluating icovamenib as an adjunct to GLP-1-based therapies in subjects who are either initiating a GLP-1 RA-based therapy or are uncontrolled on a GLP-1 RA-based therapy.

Further Preclinical Results of Icovamenib in Combination with Semaglutide

We conducted a preclinical study of two animal groups, one group of 10 ZDF rats dosed with icovamenib (day 1 through day 28) in combination with semaglutide (day 14 through day 28) and a second group of 10 ZDF rats dosed with semaglutide alone (day 14 through day 28). The ZDF rat is a type 2 diabetes animal model characterized by insulin resistance. This study evaluated the activity of icovamenib in combination with a GLP-1 RA (i.e., semaglutide) to assess key metabolic parameters in animal models including: improvements in C-peptide index, a marker of insulin secretion and glucose regulation, blood glucose, HbA1c, HOMA for insulin resistance (HOMA-IR) and HOMA-β, changes in body weight and composition, including fat and lean mass, and appetite suppression. Biomarkers were analyzed at multiple time points throughout a 28-day period.

An approximately 60% reduction in fasting blood glucose level and an approximately 50% reduction in AUC during the Oral Glucose Tolerance Test (OGTT) were observed with the icovamenib combination therapy versus semaglutide alone, indicating improved glucose metabolism (p<0.0001). The HbA1c reduction on Day 28 was greater with the combination therapy (>1%) compared to semaglutide alone (p<0.05). Insulin resistance as measured by HOMA-IR was reduced by approximately 75% with combination therapy compared to semaglutide alone (p<0.001). Combination treatment also improved beta cell function as measured by HOMA-β. Importantly, the combination therapy reduced body weight by 11.5% and fat mass by 29.5% compared to semaglutide alone. A 43% increase in lean mass compared to semaglutide alone was observed with the combination therapy.

We believe these preclinical findings support the potential of icovamenib as a complementary therapy to GLP-1 RA based therapies in diabetes treatment. The combination demonstrated enhanced glycemic control, improved insulin sensitivity, and superior weight loss benefits while preserving muscle mass, suggesting a differentiated metabolic effect.

We continue to advance the clinical development of icovamenib and plan to further assess its activity in combination with GLP-1 RA-based therapies in future clinical studies.

COVALENT-112 Type 1 Diabetes Phase II Study

COVALENT-112 is a multi-site, randomized, double-blind, placebo-controlled Phase I/II study evaluating icovamenib in healthy adults and adults with type 1 diabetes. The study’s primary endpoint assesses the mean change from baseline in stimulated C-peptide AUC at Week 12. The former clinical hold imposed in June 2024 and lifted in September 2024, had a more profound impact on the ongoing Phase II COVALENT -112 study in type 1 diabetes, where over 90% of the targeted patient population were not able to complete dosing due to the clinical hold. We are therefore planning to continue enrollment in the COVALENT-112 study so we can provide a more complete update in this patient population in 2025.

Competition

The biotechnology and pharmaceutical industries are characterized by the rapid evolution of technologies and understanding of disease etiology, intense competition and a strong emphasis on intellectual property. We believe that our approach, strategy, scientific capabilities, know-how and experience provide us with competitive advantages. In addition, we believe we are currently the only company in the United States developing irreversible covalent binders specifically against menin. More broadly, we define ourselves as targeted drug developers focused on irreversible covalent drugs and as such expect substantial competition from multiple sources, including major pharmaceutical, specialty pharmaceutical, and existing or emerging biotechnology companies, academic research institutions and governmental agencies and public and private research institutions worldwide. Many of our competitors, either alone or through collaborations, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

These companies may be or may become interested in discovery and development of irreversible covalent binders that may compete with us against menin or related targets at scale and in an integrated way. Even if they do not advance programs with the same mechanism of action as ours, these companies could develop products or product candidates that are competitive with ours or that have a superior product profile and may do so at a rapid pace. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient enrollment in clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. As a result, our competitors may discover, develop, license or commercialize products before or more successfully than we do. We face competition from segments of the pharmaceutical, biotechnology and other related markets that pursue the development of therapies that target irreversible covalent binding against protein targets of interest to us.

To our knowledge, there are no clinical-stage programs that aim to specifically regenerate insulin-producing beta cells in the islets by targeting menin for diabetes. There are over 60 approved agents and therapies being utilized to address diabetes. Such approved agents and therapies are intended to provide specific benefits to patients; however, we are not aware of any successfully addressing the root cause of diabetes, a depleted pool of functional beta cells. Several programs are targeting beta cell proliferation, including DYRK1A inhibitors. However, in addition to specific safety challenges, studies have shown that this approach may not only proliferate beta cells but also other pancreatic cells, which would not necessarily improve the ratio of alpha to beta cells in the pancreas.

Our competitors will also include companies that are or will be developing other targeted therapies, including small molecule, antibody, or protein degraders for the same indications that we are targeting. We could see a reduction or elimination in our commercial opportunity if our competitors develop and commercialize drugs that are safer, more effective, have fewer or less severe side effects, are more convenient to administer, are less expensive or with more favorable labeling than our product candidates. Our competitors also may obtain FDA or other regulatory approval for their drugs more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market. The key competitive factors affecting the success of all of our product candidates, if approved, are likely to be their potency, selectivity, inactivation of the target, therapeutic window, safety, convenience, price, the level of generic competition, our ability to market and commercialize the product candidate, and the availability of reimbursement from government and other third-party payors.

Intellectual Property

We seek to protect the intellectual property and proprietary technology that we consider important to our business, including by pursuing patent applications that cover our product candidates and methods of using the same, as well as other relevant inventions and improvements that we believe to be commercially important to the development of our business. We also rely on trade secrets, know-how and continuing technological innovation to develop and maintain our proprietary and intellectual property position. Our commercial success depends, in part, on our ability to obtain, maintain, enforce and protect our intellectual property and other proprietary rights for the technology, inventions and improvements we consider important to our business, and to defend any patents we may own or in-license in the future, prevent others from infringing any patents we may own or in-license in the future, preserve the confidentiality of our trade secrets, and operate without infringing, misappropriating or otherwise violating the valid and enforceable patents and proprietary rights of third parties. As with other biotechnology and pharmaceutical companies, our ability to maintain and solidify our proprietary and intellectual property position for our product candidates and technologies will depend on our success in obtaining effective patent claims and enforcing those claims if granted. However, our pending provisional and Patent Cooperation Treaty (PCT) applications, and any patent applications that we may in the future file or license from third parties, may not result in the issuance of patents and any issued patents we may obtain do not guarantee us the right to practice our technology or commercialize our product candidates. The PCT is a treaty with more than 150 contracting states that makes it possible to seek patent protection across multiple states by filing a single “international” application. We also cannot predict the breadth of claims that may be allowed or enforced in any patents we may own or in-license in the future. Any issued patents that we may own or in-license in the future may be challenged, invalidated, circumvented or have the scope of their claims narrowed. In addition, because of the extensive time required for clinical development and regulatory review of a product candidate we may develop, it is possible that, before any of our product candidates can be commercialized, any related patent may expire or remain in force for only a short period following commercialization, thereby limiting the protection such patent would afford the respective product and any competitive advantage such patent may provide.

The term of individual patents depends upon the date of filing of the patent application, the date of patent issuance and the legal term of patents in the countries in which they are obtained. In most countries, including the United States, the patent term is 20 years from the earliest filing date of a non-provisional patent application. In the United States, a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the United States Patent and Trademark Office (USPTO) in examining and granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier filed patent. The term of a patent claiming a new drug product may also be eligible for a limited patent term extension when FDA approval is granted, provided statutory and regulatory requirements are met. The extension period granted on a patent covering a product is typically one-half the time between the effective date of a clinical investigation involving human beings is begun and the submission date of a new drug application (NDA), plus the time between the submission date of a NDA and the ultimate approval date. The extension period cannot be longer than five years and the total patent term, including the extension period, must not exceed 14 years following FDA approval. Only one patent applicable to an approved product is eligible for the extension, and only those claims covering the approved product, a method for using it, or a method for manufacturing it may be extended. A patent that covers multiple products for which extension is sought can only be extended in connection with one of the approvals. The USPTO reviews the application for any patent term extension or restoration in consultation with the FDA. In the future, if any of our product candidates receive approval by the FDA, we expect to apply for a patent term extension on an issued patents covering the product, depending upon the length of the

clinical studies for the product and other factors. Outside the U.S., similar applications for patent term extensions or supplementary protection certificates are available in a limited number of countries. We expect to apply for such coverage where available. There can be no assurance that the USPTO or any other patent office outside the U.S. will approve any of our applications for patent term extensions or supplementary protection certificates. There can be no assurance that patents will issue from our current or future pending patent applications, or that we will benefit from any patent term extension or favorable adjustments to the terms of any patents we may own or in-license in the future. In addition, the actual protection afforded by a patent varies on a product-by-product basis, from country-to-country, and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country and the validity and enforceability of the patent. Patent term may be inadequate to protect our competitive position on our products, if approved, for an adequate amount of time.

As of December 31, 2024, we owned four issued U.S. patents, more than sixty U.S. and outside U.S. pending patent applications, directed to compositions of matter, methods of treatment, and methods of making with respect to our product candidates, including icovamenib and BMF-500.

Prosecution is a lengthy process, during which the scope of the claims initially submitted for examination by the USPTO or other foreign jurisdiction are often significantly narrowed by the time they issue, if they issue at all. Any of our pending PCT patent applications are not eligible to become issued patents until, among other things, we file national stage patent applications within 30 months in the countries 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 patent applications and any patent protection on the inventions disclosed in such PCT patent applications. Our provisional patent applications may never result in issued patents and are not eligible to become issued patents until, among other things, we file a non-provisional and/or PCT patent application within 12 months of filing the related provisional patent application. If we do not timely file non-provisional or PCT patent applications, we may lose our priority date with respect to our provisional patent applications and any patent protection on the inventions disclosed in our provisional patent applications. While we intend to timely file non-provisional and PCT patent applications relating to our provisional patent applications, and we intend to timely file national stage patent applications relating to our PCT patent applications, we cannot predict whether any of our current or future patent applications related to icovamenib, or any of our other product candidates, will issue as patents. If we do not successfully obtain patent protection, or, even if we do obtain patent protection, if the scope of the patent protection we obtain our product candidates or technology is not sufficiently broad, we will be unable to prevent others from using our technology or from developing or commercializing technology and products similar or identical to ours or other competing products and technologies. Additionally, even if any of our patent applications issue as patents, the patents covering our proprietary technologies and our product candidates would be expected to expire between 2039 to 2042.

In addition to patent applications, we rely on unpatented trade secrets, know-how and continuing technological innovation to develop and maintain our competitive position. However, trade secrets and confidential know-how are difficult to protect. In particular, we consider various aspects of our irreversible binder discovery platform to constitute our trade secrets and know-how. We seek to protect our proprietary information, in part, by executing confidentiality agreements with our collaborators and scientific advisors and non-competition, non-solicitation, confidentiality and invention assignment agreements with our employees and consultants. We cannot guarantee that we will have executed such agreements with all applicable employees and contractors, or that these agreements will afford us adequate protection of our intellectual property and proprietary information rights. In addition, our trade secrets and/or confidential know-how may become known or be independently developed by a third party or misused by any person to whom we disclose such information. These agreements may also be breached, and we may not have an adequate remedy for any such breach. Despite any measures taken to protect our intellectual property, unauthorized parties may attempt to copy aspects of our products or to obtain or use information that we regard as proprietary. Although we take steps to protect our product candidates or any future proprietary information, third parties may independently develop the same or similar proprietary information or may otherwise gain access to our proprietary information. As a result, we may be unable to meaningfully protect our trade secrets and proprietary information. For more information regarding the risks related to our intellectual property, please see “Risk Factors—Risks related to our intellectual property.”

License and Partnership Agreements

As of December 31, 2024, we did not have any license or partnership agreements related to any of our programs. As these programs and our business evolve, we may consider entering into a potential license or partnership and may explore partnerships to further advance our oncology assets while concentrating our internal resources on metabolic disorders. A potential partnership could provide non-dilutive funding and access to additional capabilities and expertise that a partner could provide to enhance the overall probability of program success.

Manufacturing

We do not have any manufacturing facilities or personnel. We currently rely, and expect to continue to rely, on third parties for the manufacture of our product candidates undergoing preclinical studies, as well as for our clinical trials. This arrangement is also expected for commercial manufacturing if our product candidates receive marketing approval. Certain of our suppliers of ingredients, raw materials, components and materials are single source suppliers. All of our product candidates are small molecules and are manufactured in synthetic processes from available starting materials. We expect to continue to develop product candidates that can be produced cost-effectively at contract manufacturing facilities.

Commercialization

Subject to receiving marketing approvals, we expect to commence commercialization activities by building a focused sales and marketing organization in the United States to sell our products. We believe that such an organization will be able to address the community of oncologists who are the key specialists in treating the patient populations for which our product candidates are being developed. Outside the United States, we expect to enter into distribution and other marketing arrangements with third parties for any of our product candidates that obtain marketing approval. We also plan to build a marketing and sales management organization to create and implement marketing strategies for any products that we market through our own sales organization and to oversee and support our sales force. The responsibilities of the marketing organization would include developing educational initiatives with respect to approved products and establishing relationships with researchers and practitioners in relevant fields of medicine.

Government Regulation

Government authorities in the United States, at the federal, state and local level, and other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, marketing, and export and import of drug products. A new drug must be approved by the FDA through the (NDA) process before it may be legally marketed in the United States. We, along with any third-party contractors, will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval of our products and product candidates. The process of obtaining regulatory approvals and the subsequent compliance with applicable federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources.

U.S. Drug Development Process

In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act (FDCA) and its implementing regulations. 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. The process required by the FDA before a drug may be marketed in the United States generally involves the following:

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completion of preclinical laboratory studies, animal studies and formulation studies in accordance with the FDA’s good laboratory practice (GLP) requirements and other applicable regulations;

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submission to the FDA of an IND, which must become effective before human clinical trials may begin;

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approval by an independent Institutional Review Board (IRB), or ethics committee at each clinical site before each trial may be initiated;

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performance of adequate and well-controlled human clinical trials in accordance with good clinical practices (GCPs), to establish the safety and efficacy of the proposed drug for its intended use;

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preparation of and submission to the FDA of an NDA after completion of all pivotal trials;

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a determination by the FDA within 60 days of its receipt of an NDA to file the application for review

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satisfactory completion of an FDA advisory committee review, if applicable;

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satisfactory completion of an FDA inspection of the manufacturing facilities at which the drug is produced to assess compliance with current good manufacturing practice (cGMP) requirements to ensure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity, and of selected clinical investigation sites to assess compliance with GCPs; and

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FDA review and approval of the NDA to permit commercial marketing of the product for particular indications for use in the United States.

Prior to beginning the first clinical trial with a product candidate in the United States, a sponsor must submit an IND to the FDA. An IND is a request for authorization from the FDA to administer an investigational new drug product to humans. The central focus of an IND submission is on the general investigational plan and the protocol(s) for clinical studies. 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 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. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial. 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 the clinical trial can begin. Submission of an IND therefore may or may not result in FDA authorization to begin a clinical trial.

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 study. Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. A separate submission to the existing IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments. Furthermore, an independent IRB for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site and must monitor the study until completed. Some studies also include oversight by an independent group of qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, which provides authorization for whether or not a study may move forward at designated check points based on access to certain data from the study and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy. Depending on its charter, this group may determine whether a trial may move forward at designated check points based on access to certain data from the trial. The FDA or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the research subjects or participants are being exposed to an unacceptable health risk.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to participants. There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

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Phase I: The product candidate is initially introduced into healthy human subjects or participants with the target disease or condition. These studies are designed to test the safety, dosage tolerance, absorption, metabolism and distribution of the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.

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Phase II: The product candidate is administered to a limited participant population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and safety risks. Multiple Phase II clinical trials may be conducted to obtain information prior to beginning larger and more expensive Phase III clinical trials.

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Phase III: The product candidate is administered to an expanded participant population to further evaluate dosage, to provide statistically significant evidence of clinical efficacy and to further test for safety, generally at multiple geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and to provide an adequate basis for product approval.

In some cases, the FDA may require, or sponsors may voluntarily pursue, additional clinical trials after a product is approved to gain more information about the product. These so-called Phase IV studies may be conducted after initial marketing approval, and may be used to gain additional experience from the treatment of participants in the intended therapeutic indication. In certain instances, the FDA may mandate the performance of Phase IV clinical trials as a condition of approval of an NDA.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the drug and finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, the manufacturer must develop methods for testing the identity, strength, quality and purity of the final drug. In addition, 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.

While the IND is active and before approval, progress reports summarizing the results of the clinical trials and non-clinical studies performed since the last progress report must be submitted at least annually to the FDA, and written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected adverse events, findings from other studies suggesting a significant risk to humans exposed to the same or similar drugs, findings from animal or in vitro testing suggesting a significant risk to humans, and any clinically important increased incidence of a serious suspected adverse reaction compared to that listed in the protocol or investigator brochure.

In addition, during the development of a new drug, 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 II, and before an NDA is submitted. Meetings at other times may be requested. These meetings can provide an opportunity for the sponsor to share information about the data gathered to date, for the FDA to provide advice, and for the sponsor and the FDA to reach agreement on the next phase of development. Sponsors typically use the meetings at the end of the Phase II trial to discuss Phase II clinical results and present plans for the pivotal Phase III clinical trials that they believe will support approval of the new drug.

U.S. Review and Approval Process

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, preclinical and other non-clinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the chemistry of the drug, proposed labeling and other relevant information are submitted to the FDA as part of an NDA requesting approval to market the product. Data can come from company-sponsored clinical studies intended to test the safety and effectiveness of a use of the product, or from a number of alternative sources, including studies initiated by independent investigators. The submission of an NDA is subject to the payment of substantial user fees; a waiver of such fees may be obtained under certain limited circumstances. Additionally, no user fees are assessed on NDAs for products designated as orphan drugs, unless the product also includes a non-orphan indication.

The FDA conducts a preliminary review of all NDAs 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 NDA for filing. In this event, the NDA must be resubmitted with the additional information. The resubmitted application also is subject to review before the FDA accepts it for filing. Once filed, the FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP-compliant to assure and preserve the product’s identity, strength, quality and purity. Under the Prescription Drug User Fee Act (PDUFA) guidelines that are currently in effect, the FDA has a goal of ten months from the filing date to complete a standard review of an NDA for a drug that is a new molecular entity. This review typically takes twelve months from the date the NDA is submitted to FDA because the FDA has approximately two months to make a “filing” decision after it the application is submitted.

The FDA may refer an application for a novel drug to an advisory committee. 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.

Before approving an NDA, the FDA will typically 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 and adequate to assure consistent production of the product within required specifications. Additionally, before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCPs. If the FDA determines that the application, manufacturing process or manufacturing facilities are not acceptable, it will outline the deficiencies in the submission and often will request additional testing or information. Notwithstanding the submission of any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

After the FDA evaluates an NDA and conducts inspections of manufacturing facilities where the investigational product and/or its drug substance will be produced, the FDA may issue an approval letter or a Complete Response Letter (CRL). An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A CRL will describe all of the deficiencies that the FDA has identified in the NDA, except that where the FDA determines that the data supporting the application are inadequate to support approval, the FDA may issue the CRL without first conducting required inspections and/or reviewing proposed labeling. In issuing the CRL, the FDA may recommend actions that the applicant might take to place the NDA in condition for approval, including requests for additional information or clarification. The FDA may delay or refuse approval of an NDA if applicable regulatory criteria are not satisfied, require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product.

If regulatory approval of a product is granted, such approval will be granted for particular indications and may entail limitations on the indicated uses for which such product may be marketed. For example, the FDA may approve the NDA with a risk evaluation and mitigation strategy (REMS) to ensure the benefits of the product outweigh its risks. A REMS is a safety strategy to manage a known or potential serious risk associated with a medicine and to enable patients to have continued access to such medicines by managing their safe use, and could include medication guides, physician communication plans, or elements to assure safe use (ETASU), such as restricted distribution methods, patient registries, and other risk minimization tools. If the FDA concludes a REMS is needed, the sponsor of the NDA must submit a proposed REMS; the FDA will not approve the NDA without a REMS, if required. The FDA also may condition approval on, among other things, changes to proposed labeling or the development of adequate controls and specifications. The FDA may also require one or more Phase IV post-market studies and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization, and may limit further marketing of the product based on the results of these post-marketing studies.

In addition, the Pediatric Research Equity Act (PREA) requires a sponsor to conduct pediatric clinical trials for most drugs, for a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration. Under PREA, original NDAs and supplements must contain a pediatric assessment unless the sponsor has received a deferral or waiver. The required assessment must evaluate the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The sponsor or FDA may request a deferral of pediatric clinical trials for some or all of the pediatric subpopulations. A deferral may be granted for several reasons, including a finding that the drug is ready for approval for use in adults before pediatric clinical trials are complete or that additional safety or effectiveness data needs to be collected before the pediatric clinical trials begin. The FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment, fails to keep a deferral current or fails to submit a request for approval of a pediatric formulation.

Expedited Development and Review Programs

The FDA offers a number of expedited development and review programs for qualifying product candidates. For example, the Fast Track program is intended to expedite or facilitate the process for reviewing new products that are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition. Fast Track designation applies to the combination of the product and the specific indication for which it is being studied. The sponsor of a Fast Track product has opportunities for more frequent interactions with the applicable FDA review team during product development and, once an NDA 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 portions of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the portions of the NDA, the FDA agrees to accept portions of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first portions of the NDA.

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 available 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 I and an organizational commitment to expedite the development and review of the product candidate, including involvement of senior managers.

Any marketing application for a drug 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 the FDA review and approval process, such as priority review and accelerated approval. A product candidate is eligible for priority review if it is designed to treat a serious or life-threatening disease or condition, and if approved, would provide a significant improvement in safety or effectiveness compared to available alternatives for such disease or condition. For new-molecular-entity NDAs, 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.

Additionally, product candidates studied for their safety and effectiveness in treating serious or life-threatening diseases or conditions may receive accelerated approval upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. As a condition of accelerated approval, the FDA will generally require the sponsor to perform adequate and well-controlled post-marketing clinical studies to verify and describe the anticipated effect on irreversible morbidity or mortality

or other clinical benefit. Under the Food and Drug Omnibus Reform Act of 2022 (FDORA), the FDA is permitted to 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 drug or indication approved under accelerated approval if, for example, the confirmatory trial fails to verify the predicted clinical benefit of the product. In addition, for products being considered for accelerated approval, the FDA generally requires, unless otherwise informed by the agency, that all advertising and promotional materials intended for dissemination or publication within 120 days of marketing approval be submitted to the agency for review during the pre-approval review period.

Fast Track designation, Breakthrough Therapy designation, priority review, and accelerated approval 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.

Orphan Drug Designation and Exclusivity

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, defined as a disease or condition with a patient population of fewer than 200,000 individuals in the United States, or a patient population of 200,000 or more individuals in the United States and when there is no reasonable expectation that the cost of developing and making available the drug in the United States will be recovered from sales in the United States for that drug. Orphan drug designation must be requested before submitting an NDA. After the FDA grants orphan drug designation, the generic identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.

If a product that has orphan drug 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, including a full NDA, to market the same drug for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or in instances of drug supply issues. Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same disease or condition, or the same drug for a different disease or condition. Among the other potential benefits of orphan drug designation are tax credits for certain research and a waiver of the NDA application user fee.

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. In addition, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or, as noted above, if a second applicant demonstrates that its product is clinically superior to the approved product with orphan exclusivity or the manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Post-approval Requirements

Drug 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 record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product. After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval. There also are continuing, annual program fees for any marketed products. Drug manufacturers and their subcontractors and those supplying products, ingredients, and components are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP, which impose certain procedural and documentation requirements upon us and our third-party manufacturers. 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 requirements. Manufacturers and other parties involved in the drug supply chain for prescription drug products must also comply with product tracking and tracing requirements and for notifying the FDA of counterfeit, diverted, stolen and intentionally adulterated products or products that are otherwise unfit for distribution in the United States. 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.

The FDA may withdraw approval 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 studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things:

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restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;

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fines, warning letters, or untitled letters;

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clinical holds on clinical studies;

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refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product approvals;

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product seizure or detention, or refusal to permit the import or export of products;

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consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs;

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mandated modification of promotional materials and labeling and the issuance of corrective information;

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the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or

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injunctions or the imposition of civil or criminal penalties.

The FDA closely regulates the marketing, labeling, advertising and promotion of drug products. A company can make only those claims relating to safety and efficacy, purity and potency that are approved by the FDA and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses. Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties. Physicians may prescribe, in their independent professional medical judgment, legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products. However, companies may share truthful and not misleading information that is otherwise consistent with a product’s FDA-approved labelling.

From time to time, legislation is drafted, introduced, passed in Congress and signed into law that could significantly change the statutory provisions governing the approval, manufacturing, and marketing of products regulated by the FDA. In addition to new legislation, FDA regulations, guidances, and policies are often revised or reinterpreted by the agency in ways that may significantly affect the manner in which pharmaceutical products are regulated and marketed.

Other United States 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 United States in addition to the FDA, which may include the Centers for Medicare and Medicaid Services (CMS), other divisions of the Department of Health and Human Services (HHS), the Department of Justice, the Drug Enforcement Administration, the Consumer Product Safety Commission, the Federal Trade Commission (FTC), the Occupational Safety and Health Administration, the Environmental Protection Agency and state and local governments and governmental agencies.

United States Patent Term Restoration and Marketing Exclusivity

Depending upon the timing, duration and specifics of FDA approval of our future product candidates, some of our United States 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 restoration of the patent term of up to five years as compensation for patent term lost during the FDA regulatory review process. Patent-term restoration, however, cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date and only those claims covering such approved drug product, a method for using it or a method for manufacturing it may be extended. The patent-term restoration period is generally one-half the time between the effective date of an IND and the submission date of an NDA plus the time between the submission date of an NDA and the approval of that application, except that the review period is reduced by any time during which the applicant failed to exercise due diligence. Only one patent applicable to an approved drug is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent. The U.S. Patent and Trademark Office, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.

Regulatory exclusivity provisions under the FDCA also can delay the submission or the approval of certain applications. The FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to gain approval of an NDA for a new chemical entity. A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance. During the exclusivity period, the FDA may not accept for review an abbreviated NDA (ANDA), or a 505(b)(2) NDA submitted by another company for another version of such drug where the applicant does not own or have a legal right of reference to all the data required for approval. However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement.

The FDCA also provides three years of exclusivity for an NDA, 505(b)(2) NDA or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, new indications, dosages or strengths of an existing drug. This three-year exclusivity covers only the conditions of use associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for drugs containing the original active agent for other conditions of use. Five-year and three-year exclusivity will not delay the submission or approval of a full NDA. However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

In addition, drugs can also obtain pediatric exclusivity in the United States. Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms. This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request” for such a study.

Other Healthcare Laws

Our business operations and current and future arrangements with investigators, healthcare professionals, consultants, third-party payors, patient organizations and customers may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations. These laws may constrain the business or financial arrangements and relationships through which we conduct our operations, including how we research, market, sell and distribute our product candidates, if approved. The laws that may affect our ability to operate include, but are not limited to:

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the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying any remuneration (including any kickback, bribe, or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce, or in return for, either the referral of an individual, 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 a federal healthcare program, such as the Medicare and Medicaid programs. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. Violations are subject to civil and criminal fines and penalties for each violation, plus up to three times the remuneration involved, imprisonment, and exclusion from government healthcare programs;

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federal civil and criminal false claims laws, including the False Claims Act (FCA), which can be enforced through civil “qui tam” or “whistleblower” actions, and civil monetary penalty laws, which 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 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 money to the federal government; or knowingly concealing or knowingly and improperly avoiding or decreasing such an obligation. Manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. In addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the FCA. The FCA also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the FCA and to share in any monetary recovery;

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the federal Health Insurance Portability and Accountability Act of 1996 (HIPAA), which created new federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters. Similar to the federal Anti-Kickback Statute, a person or entity can be found guilty

of violating these statutes without actual knowledge of the statutes or specific intent to violate them in order to have committed a violation;

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HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (HITECH), imposes requirements on certain covered healthcare providers, health plans and healthcare clearinghouses as well as their respective business associates that perform services for them that involve the use, or disclosure of, individually identifiable health information, relating to the privacy, security and transmission of individually identifiable health information without appropriate authorization. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, 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 attorneys’ fees and costs associated with pursuing federal civil actions. Even when HIPAA does not apply, according to the FTC, failing to take appropriate steps to keep consumers’ personal information secure constitutes unfair acts or practices in or affecting commerce in violation of Section 5(a) of the FTC Act, 15 U.S.C. § 45(a). 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;

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the federal Physician Payment Sunshine Act, created under the Patient Protection and Affordable Care Act of 2010, as amended (ACA) and its implementing regulations, which requires manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to HHS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other licensed health care practitioners and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members;

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California’s California Consumer Privacy Act (CCPA), which went into effect on January 1, 2020, which affords consumers expanded privacy protections. For example, the CCPA gives California residents expanded rights to access and require deletion of their personal information, opt-out of certain personal information sharing, and receive detailed information about how their personal information is used. The CCPA also provides for civil penalties for violations, as well as a private right of action for data breaches that may increase our risk to data breach class action litigation. The CCPA was expanded substantially on January 1, 2023, when the California Privacy Rights Act of 2020 (CPRA) became fully operative. The CPRA, among other things, gives California residents the ability to limit use of certain sensitive personal information, further restrict the use of cross-contextual advertising, establish restrictions on the retention of personal information, expand the types of data breaches subject to the CCPA’s private right of action, provide for increased penalties for CPRA violations concerning California residents under the age of 16, and establish a new California Privacy Protection Agency to implement and enforce the new law;

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federal government price reporting laws, which require us to calculate and report complex pricing metrics in an accurate and timely manner to government programs;

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federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; and

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analogous state and foreign laws and regulations, such as state and foreign 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, compensations 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.

Coverage and Reimbursement

Sales of any product depend, in part, on the extent to which such product will be covered by third-party payors, such as federal, state, and foreign government healthcare programs, commercial insurance and managed healthcare organizations, and the level of reimbursement for such product by third-party payors. Decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a plan-by-plan basis. These third-party payors are increasingly reducing reimbursements for medical products, drugs and services.

Factors payors consider in determining reimbursement are based on whether the product is:

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a covered benefit under its health plan;

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safe, effective and medically necessary;

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appropriate for the specific patient;

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cost-effective; and

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neither experimental nor investigational.

No uniform policy for coverage and reimbursement for products exists among third-party payors in the U.S. Therefore, coverage and reimbursement for products can differ significantly from payor to payor. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our product candidates to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. Furthermore, rules and regulations regarding reimbursement change frequently, in some cases on short notice, and we believe that changes in these rules and regulations are likely.

In addition, the U.S. government, state legislatures and foreign governments have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement and requirements for substitution of generic products. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit sales of any product. Decreases in third-party reimbursement for any product or a decision by a third-party payor not to cover a product could reduce physician usage and patient demand for the product and also have a material adverse effect on sales.

Healthcare Reform

In 2010, the ACA was enacted, which substantially changed the way healthcare is financed by both governmental and private insurers, and significantly affected the pharmaceutical industry. The ACA contained a number of provisions, including those governing enrollment in federal healthcare programs, reimbursement adjustments and changes to fraud and abuse laws. For example, the ACA:

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increased the minimum level of Medicaid rebates payable by manufacturers of brand name drugs from 15.1% to 23.1% of the average manufacturer price;

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required collection of rebates for drugs paid by Medicaid managed care organizations;

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required manufacturers to participate in a coverage gap discount program, under which they must agree to offer 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 (a requirement later replaced under the Inflation Reduction Act of 2022 (IRA) by the Medicare Part D manufacturer discount program); and

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imposed a non-deductible annual fee on pharmaceutical manufacturers or importers who sell “branded prescription drugs” to specified federal government programs.

There has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices. Specifically, there have been several recent U.S. Congressional inquiries and proposed federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drugs. Both the Trump administration and Congress have indicated that they will continue to seek new legislative and executive measures to control drug costs. In addition, other legislative and regulatory changes have been proposed and adopted in the United States since the ACA was enacted:

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The U.S. Budget Control Act of 2011, among other things, included aggregate reductions of Medicare payments to providers of two percent per fiscal year that remain in effect through 2031.

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The U.S. American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

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The American Rescue Plan Act of 2021 eliminates the statutory Medicaid drug rebate cap, previously set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024. Due to the Statutory Pay-As-You-Go Act of 2010, estimated budget deficit increases resulting from the American Rescue Plan Act of 2021, and subsequent legislation, Medicare payments to providers were further reduced starting in 2025 absent further legislation.

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The IRA also includes several provisions that will impact our business 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 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. Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have one orphan designation and for which the only approved indication is for that disease or condition. If a product receives multiple orphan designations or has multiple approved indications, it may not qualify for the orphan drug exemption. The implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA’s Medicare drug price negotiation program. The effect of IRA on our business and the healthcare industry in general is not yet known.

Individual states have also been increasingly active in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. In addition, regional health care authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other health care programs. We expect that additional state and federal healthcare reform measures will be adopted in the future, particularly in light of the new presidential administration, any of which could limit the amounts that federal and state governments will pay for healthcare products and services.

Human Capital Resources

As of December 31, 2024, we had 106 full-time employees, 79 of whom were engaged in research and development activities. We believe we have good relationships with our employees. None of our employees are represented by a labor union or covered under a collective bargaining agreement.

Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and additional employees. The principal purposes of our equity incentive plans are to attract, retain and motivate selected employees, consultants and directors through the granting of stock-based compensation awards.

Corporate Information

We were established in the state of Delaware in August 2017 as Biomea Fusion, LLC. In December 2020, all outstanding membership interests in Biomea Fusion, LLC were converted into equity interests in the Company.

Our principal executive offices are located at 900 Middlefield Road, 4th Floor, Redwood City, California 94063, and our telephone number is (650) 980-9099. Our website address is www.biomeafusion.com. We do not incorporate the information on or accessible through our website into this Annual Report on Form 10-K, and you should not consider any information on, or that can be accessed through, our website a part of this Annual Report on Form 10-K.

Biomea Fusion, Inc., the Biomea logo, FUSIONTM System and our other registered or common law trademarks, trade names or service marks appearing in this Annual Report on Form 10-K are owned by us. This Annual Report on Form 10-K contains references to our trademarks and to trademarks belonging to other entities. Solely for convenience, trademarks and trade names referred to in this Annual Report on Form 10-K, including logos, artwork and other visual displays, generally appear without the ® or TM symbols, but such references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensor to these trademarks and trade names. We do not intend our use or display of other companies’ trade names or trademarks to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

Available Information

Our Annual Reports on Form 10‐K, Quarterly Reports on Form 10‐Q, Current Reports on Form 8‐K, proxy and information statements and amendments to reports filed pursuant to Sections 13(a), and 15(d) of the Securities Exchange Act of 1934, as amended (Exchange Act) are filed with the SEC. We are subject to the informational requirements of the Exchange Act and file or furnish reports, proxy statements and other information with the SEC. The SEC maintains an Internet site that contains

reports, proxy and information statements and other information regarding issuers that file electronically with the SEC at www.sec.gov. Such documents and other information filed by us with the SEC are available free of charge on the “Investors & Media” section of our website when such reports are available on the SEC’s website. The contents of websites referred to above are not incorporated into this Annual Report on Form 10-K. Further, our references to the URLs for these websites are intended to be inactive textual references only.

Item 1A. Risk Factors

Our business is subject to various risks and uncertainties, including those described below, that we believe apply to our business and the industry in which we operate. You should carefully consider these risks, as well as the other information in this Annual Report on Form 10-K, including our financial statements and the related notes and “Management’s Discussion and Analysis of Financial Condition and Results of Operations.” The occurrence of any of the events or developments described below could have a material adverse effect on our business, results of operations, financial condition, prospects and stock price. Additional risks and uncertainties not presently known to us or that we currently deem immaterial may also impair our business.

Risks Related to Our Limited Operating History, Business, Financial Condition, Results of Operations, and Need for Additional Capital

We have a limited operating history, limited experience in conducting clinical trials, have not completed any clinical trials, have no products approved for commercial sale, and have not generated any revenue, which may make it difficult for you to evaluate our current business and likelihood of success and viability.

We are a clinical-stage biotechnology company with a limited operating history with which investors can evaluate our business and prospects. We commenced operations in August 2017, have not completed any clinical trials, have no products approved for commercial sale and have never generated any revenue, and our operations to date have been primarily limited 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, preparing for and initiating our initial clinical trials, and establishing arrangements with third parties for the manufacture of initial quantities of product candidates. We currently have two product candidates, icovamenib and BMF-500, under investigation in clinical trials, with the first patient dosed with BMF-500 in October 2023. Our remaining product candidates, including BMF-650, are in the discovery or preclinical development stage.

We have limited experience as a company in conducting clinical trials and have not successfully completed the clinical development of any product candidates to date. Consequently, any predictions you 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 company with a limited operating history, 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 have not yet demonstrated an ability to successfully overcome such risks and difficulties, or to make such a transition. If we do not adequately address these risks and difficulties or successfully make such a transition, our business will suffer.

We expect our financial condition and results of operations to continue to fluctuate significantly from quarter to quarter and year to year due to a variety of factors, many of which are beyond our control. Accordingly, you should not rely upon the results of any quarterly or annual periods as indications of future operating performance.

We have incurred significant net losses in each period since our inception, and we expect to incur significant net losses for the foreseeable future.

Investment in biopharmaceutical product development is a highly speculative undertaking and entails substantial upfront capital expenditures and significant risk that any potential product candidate will fail to demonstrate adequate efficacy or an acceptable safety profile, gain regulatory approval, and become commercially viable. We are early in our development efforts and have not yet completed the development of any of our product candidates. We have no products approved for commercial sale and have not generated any revenue from product sales to date, and we continue to incur significant research and development and other expenses related to our ongoing operations. Even if we succeed in receiving marketing approval for and commercializing one or more of our product candidates, we expect that we will continue to incur substantial research and development and other expenses in order to discover, develop and market additional potential products. We have financed our operations primarily through sales of our common stock and convertible preferred stock.

We have incurred significant net losses in each reporting period since we commenced operations in August 2017. Our net losses were $138.4 million and $117.3 million, for the years ended December 31, 2024 and 2023, respectively. As of December 31, 2024, we had an accumulated deficit of $387.3 million. Substantially all of our losses have resulted from expenses incurred in connection with our research and development programs and from general and administrative costs

associated with our operations. We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase substantially if and as we:

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continue our research and development efforts and submit additional INDs;

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continue the clinical development of icovamenib for the treatment of patients with type 1 and type 2 diabetes;

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explore the potential clinical utility of icovamenib in other metabolic disorders, including pre-diabetes and obesity;

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continue the clinical development of BMF-500, a covalent inhibitor of FMS-like tyrosine kinase 3 (FLT3);

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continue the preclinical development and initiate clinical development of BMF-650;

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continue our efforts to develop product candidates from our FUSIONTM System discovery platform;

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conduct preclinical studies and initiate and conduct clinical trials;

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seek marketing approvals for any product candidates that successfully complete clinical trials;

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experience any delays or encounter any issues with any of the above, including but not limited to failed studies, complex results,

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safety issues, or other regulatory challenges;

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establish a sales, marketing, and distribution infrastructure and scale-up manufacturing capabilities, whether alone or with third parties, to commercialize any product candidates for which we may obtain regulatory approval, if any;

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obtain, expand, maintain, enforce, and protect our intellectual property portfolio;

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hire additional clinical, regulatory, and scientific personnel; and

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operate as a public company.

Because of the numerous risks and uncertainties associated with biopharmaceutical product development, we are unable to accurately predict the timing or amount of increased expenses we will incur or when, if ever, we will be able to achieve profitability. Even if we 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. 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.

We have not generated any revenue from our product candidates and may never generate revenue or be profitable. Our ability to generate revenue and achieve profitability depends significantly on our ability to achieve several objectives relating to the discovery and development of our product candidates.

Our ability to become profitable depends upon our ability to generate revenue. We have not received marketing approval for any product candidate, and we have not generated any revenue from any product sales or other sources since our inception. We do not expect to generate revenue unless or until we successfully complete preclinical and clinical development and obtain regulatory approval of, and then successfully commercialize, at least one product candidate. Icovamenib, our lead product candidate, is in the early stages of clinical development. As such, we face significant translational risk as our product candidates advance further in clinical development, and promising results in preclinical studies or early clinical trials may not be replicated in later-stage clinical trials. If approved, Icovamenib is not intended as a chronic therapy for insulin deficient diabetes, which could further limit our ability to achieve profitability. All of our current and future product candidates will require preclinical and clinical development, 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. Our ability to generate revenue depends on a number of factors, including, but not limited to:

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timely initiation and completion of our preclinical studies and clinical trials for icovamenib, BMF-500, BMF-650 and our future product candidates, which may be significantly slower or cost more than we currently anticipate and will depend substantially upon the performance of third-party contractors;

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establishing and maintaining relationships with contract research organizations (CROs) and clinical sites for the ongoing clinical and preclinical development of icovamenib and BMF-650 and any future product candidates;

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our ability to complete IND-enabling studies, and successfully submit and receive authorization to proceed under INDs or comparable regulatory applications;

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whether we are required by the FDA or other comparable 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;

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our ability to demonstrate to the satisfaction of the FDA and comparable foreign regulatory authorities the safety, efficacy, consistent manufacturing quality, and acceptable risk-benefit profile of our small molecule product candidates or any future product candidates;

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the prevalence, duration, and severity of potential side effects or other safety issues experienced with our product candidates or future product candidates, if any;

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the timely receipt of necessary regulatory approvals from the FDA and comparable foreign regulatory authorities;

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the willingness of physicians, operators of clinics, and patients to utilize or adopt any of our product candidates or future product candidates over alternative or more conventional therapies;

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the actual and perceived availability, cost, risk profile and side effects and efficacy of our product candidates, if approved, relative to existing and future alternative therapies in our target indications, including diabetes and obesity, and competitive product candidates and technologies;

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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 cGMP;

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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 approved for marketing, reimbursement, sale and distribution in such countries and territories, whether alone or in collaboration with others;

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patient demand for our current product candidates and any future product candidates, if approved;

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our ability to establish and enforce intellectual property rights in and to our product candidates or any future product candidates;

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obtaining coverage and adequate reimbursement by third-party payors for our product candidates;

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addressing any competing therapies and technological and market developments; and

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attracting, hiring, and retaining qualified personnel.

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 commercializing our product candidates. Even if we are able to commercialize our product candidates, we may not achieve profitability soon after generating product sales, if ever. 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 adequate funding.

Due to the significant resources required for the development of our product candidates, we must prioritize development of certain product candidates and/or certain indications. 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.

We are currently focused on the discovery and development of novel covalent small molecules to treat patients with diabetes and obesity. We seek to maintain a process of prioritization and resource allocation among our programs to maintain a balance between advancing our current product candidates and any future product candidates. Although we had previously pursued the development of icovamenib in cancer and metabolic diseases, in January 2025, we announced that our strategic focus for icovamenib will be in metabolic disorders and that we will conclude our studies exploring icovamenib’s potential in oncology and explore partnerships to advance our oncology assets.

Our decisions concerning the allocation of research, development, collaboration, management, and financial resources toward particular product candidates or therapeutic areas may not lead to the development of any viable commercial product and may divert resources away from better opportunities with other therapeutic platforms or product candidates or for other indications that later prove to have greater commercial potential or a greater likelihood of success. Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities. If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through future 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. In addition, if our determination to focus our internal resources on the development of icovamenib in metabolic disorders and seek partnerships to advance our oncology assets does not lead to clinical or commercial success, or we otherwise make incorrect determinations regarding the viability or market potential of any of our programs or product candidates or misread trends in the diabetes or obesity disease treatment landscape or in the pharmaceutical, biopharmaceutical or biotechnology industry more generally, our business, financial condition and results of operations could be materially adversely affected.

Since our inception, we have used substantial amounts of cash to fund our operations, and our expenses will increase substantially in the foreseeable future in connection with our ongoing activities, particularly as we continue the research and development of, initiate and conduct clinical trials of, and seek marketing approval for our product candidates. Developing biopharmaceutical products, including conducting preclinical studies and clinical trials, is a very time-consuming, expensive and uncertain process that takes years to complete. Our operations have consumed significant amounts of cash since inception, and we expect our expenses to increase in connection with our ongoing activities, particularly as we conduct clinical trials of, and seek marketing approval for our current product candidates and advance our future product candidates. Even if one or more of the product candidates that we develop is approved for commercial sale, we anticipate incurring significant costs associated with sales, marketing, manufacturing, and distribution activities. Our expenses could increase beyond expectations if we are required by the FDA or other regulatory agencies to perform preclinical studies or clinical trials in addition to those that we currently anticipate. Other unanticipated costs may also arise. Because the design and outcome of our ongoing and planned clinical trials are highly uncertain, we cannot reasonably estimate the actual amount of resources and funding that will be necessary to successfully complete the development and commercialization of any product candidate we develop. We also expect to incur additional costs associated with our continuing operation as a public company. Accordingly, we will need to obtain substantial additional funding in order to continue our operations.

As of December 31, 2024, we had $58.6 million in cash, cash equivalents and restricted cash. Based on our current operating plan, we believe that our existing cash and cash equivalents, and restricted cash as of December 31, 2024, without any future financing, will not be sufficient for us to continue as a going concern for at least one year from the issuance date of the financial statements appearing elsewhere in this Annual Report on Form 10-K. Our estimate as to how long we expect our existing capital resources to be able to continue to fund our operations is based on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we currently expect. Changing circumstances, some of which may be beyond our control, could cause us to consume capital significantly faster than we currently anticipate, and we may need to seek additional funds sooner than planned through public or private equity offerings, debt financings, collaborations and licensing arrangements or other sources. Such financing may dilute our stockholders or restrict our operating activities. To the extent we raise additional funds by issuing equity securities, our stockholders may experience dilution. Any future debt financing into which we enter may impose upon us additional covenants that restrict our operations, including limitations on our ability to incur liens or additional debt, pay dividends, repurchase our common stock, make certain investments and engage in certain merger, consolidation, or asset sale transactions. Any debt financing or additional equity that we raise may contain terms that are not favorable to us or our stockholders. If we are unable to raise additional funds when needed, we may be required to delay, reduce, or terminate some or all of our development programs and clinical trials. We may also be required to sell or license other rights to our product candidates in certain territories or indications that we would prefer to develop and commercialize ourselves. In addition, we may seek additional capital due to favorable market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans. If we raise additional funds through upfront payments or milestone payments pursuant to strategic collaborations with third parties, we may have to relinquish valuable rights to our product candidates or grant licenses on terms that are not favorable to us. In addition, we may seek additional capital due to favorable market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans.

Our future capital requirements depend on many factors, including but not limited to:

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the scope, timing, progress, duration, costs and results of our clinical trials, drug discovery, preclinical development activities, and laboratory testing for our product candidates;

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the number and scope of clinical programs we decide to pursue;

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the scope and costs of manufacturing development and commercial manufacturing activities;

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the extent to which we discover and develop additional product candidates;

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the cost, timing, and outcome of regulatory review of our product candidates;

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the cost and timing of establishing sales and marketing capabilities, if any of our product candidates receive marketing approval;

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the costs of preparing, filing, and prosecuting patent applications, maintaining and enforcing our intellectual property rights, and defending intellectual property-related claims;

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our ability to establish and maintain collaborations on favorable terms, if at all;

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licensing, or other arrangements into which we may enter in the future, including the timing of receipt of any milestone or royalty payments under these agreements;

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the timing, receipt, and amount of sales from our potential products;

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our need and ability to hire additional management, scientific, and medical personnel;

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our need to implement additional internal systems and infrastructure, including financial and reporting systems;

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our efforts to enhance operational systems and our ability to attract, hire, and retain qualified personnel, including personnel to support the development of our product candidates;

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the costs associated with being a public company;

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the cost associated with commercializing our product candidates, if they receive regulatory approval;

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our ability to establish and maintain strategic collaborations and other similar partnerships for the development and commercialization of our product candidates; and

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the impact of adverse global economic conditions on our business, which may exacerbate the magnitude of the factors discussed above.

We do not have any committed external source of funds and adequate additional financing may not be available to us on acceptable terms, or at all. In addition, our ability to raise additional capital may be adversely impacted by potential worsening global economic and political conditions, inflationary pressures, increases in interest rates and disruptions to and volatility in the credit and financial markets in the United States and worldwide or other factors.

There is substantial doubt about our ability to continue as a going concern.

BMEA US Equity

BMEA · 10-K · period ended 2024-12-31

Item 1. Business

Item 1A. Risk Factors

BMEA US Equity☆

BMEA · 10-K · period ended 2024-12-31

Item 1. Business

Item 1A. Risk Factors

BMEA US Equity