10-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K

(Mark One)

For the fiscal year ended December 31, 2023

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, 2023, was $596,910,000.

The number of shares of Registrant’s Common Stock outstanding as of March 21, 2024 was 35,889,360.

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, 2023 pursuant to Regulation 14A in connection with the Registrant’s 2024 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 42

Item 1B. Unresolved Staff Comments 97

Item 1C. Cybersecurity 97

Item 2. Properties 98

Item 3. Legal Proceedings 98

Item 4. Mine Safety Disclosures 98

PART II

Item 6. Selected Financial Data 99

Item 7A. Quantitative and Qualitative Disclosures About Market Risk 108

Item 8. Financial Statements and Supplementary Data 108

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 investments 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 investments;

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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 (INDs) 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 pandemics or other related disruptions on our business;

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unfavorable global economic conditions, including inflationary pressures, market volatility, 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 Securities and Exchange Commission, or SEC, before making investment decisions regarding our common stock.

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We have a limited operating history, 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, preclinical and clinical development is focused on the development of novel covalent small-molecule therapies to treat patients with genetically-defined cancers and metabolic diseases, and the approach we are taking to discover and develop such binders is novel, may never lead to marketable products and may not ultimately represent a significant 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, BMF-219 and BMF-500. If we are unable to advance BMF-219, BMF-500 or any of our future product candidates through clinical development, obtain regulatory approval and ultimately commercialize BMF-219, 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 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 biopharmaceutical company focused on the discovery and development of oral covalent small molecule drugs to treat patients with metabolic diseases and genetically defined cancers. 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 covalent small molecule product candidates.

Our lead product candidate, BMF-219, built from the FUSIONTM System, is an orally bioavailable, potent and selective covalent inhibitor of menin. Menin is a transcriptional scaffold protein that has no intrinsic enzymatic activity but facilitates signal transduction via crosstalk with various direct and indirect binding partners to regulate gene transcription and cell signaling to drive specific biological functions. In a cell type, tissue, and environment-specific manner, menin-related binding partners, genes, proteins, and regulated pathways could include JunD, MLL, NPM1, MYC, Smad, Runx1, estrogen receptor, PPAR-gamma, PRMT5, NFkB, Sirt1, EZH2, FLT3, Pbk, cyclins, cyclin dependent kinases (CDKs), cyclin dependent kinase inhibitors (CDKIs), heat shock proteins (HSPs), AKT, B-catenin, Hoxa9, Meis1, MYB, LEDGF, Gastrin, TGF-β, FOXO, and Prolactin. The reversible menin-MLL interaction inhibitors currently in clinical development by other companies primarily drive their clinical effect via interfering with the interaction of MLL with menin. In contrast, BMF-219 is designed to broadly impact menin’s interaction with additional binding partners that are known to contribute to various pathologies. We currently have clinical trials of BMF-219 underway in patients with type 1 and type 2 diabetes as well as patients with liquid and solid tumors.

In pancreatic beta-cells, menin acts as a checkpoint to regulate beta cell proliferation. In a hyperglycemic state, the reduction of functional menin protein levels has been shown by Biomea and academic groups to drive beta cell specific proliferation in pancreatic islets and restore glycemic control (in animal models). In preclinical studies, the administration of BMF-219 has also produced a pronounced effect in models of diabetes, normalizing glucose levels in rats during treatment that is sustained after drug washout, and driving replication of beta cells in ex vivo human islets that increase insulin secretion. Thus, we believe that in people with uncontrolled diabetes, the inhibition of menin by BMF-219 has the potential to enable the proliferation, preservation, and reactivation of healthy, functional beta cells capable of producing insulin, thereby leading to improvements in long-term glycemic control. BMF-219 is currently in Phase 2 clinical trials in type 2 diabetes (COVALENT-111) and type 1 diabetes (COVALENT-112).

Menin, in complex with specific binding partners, is also an important transcriptional regulator of oncogenic signaling in multiple cancers. For example, in AML mutations or genetic rearrangements, menin binding partners MLLr and NMP1 are known oncogenic drivers of the disease. In other liquid and solid tumor types, signal transduction through menin binding partners MYC and JunD have been implicated in driving tumor growth. Across a range of liquid and solid tumor models studies, the administration of BMF-219 has resulted in robust anti-tumor responses and has been generally well-tolerated. As of December 31, 2023, BMF-219 is being evaluated in liquid and solid tumors across two ongoing clinical trials, COVALENT-101 and COVALENT-102.

Beyond BMF-219, we are utilizing our novel FUSIONTM System to engineer potentially differentiated covalent investigational therapies against disease drivers. In May 2022, we announced the nomination of our second development candidate, BMF-500, a covalent inhibitor of FMS-like tyrosine kinase 3 (FLT3). We announced the U.S. Food and Drug Administration (FDA) clearance of Investigational New Drug application (IND) for BMF-500 in relapsed or refractory (R/R) acute leukemias (AML) in May 2023, and we dosed our first patient in October 2023. BMF-500 is being evaluated in R/R AML clinical trial, COVALENT-103.

We are currently advancing additional preclinical covalent programs for the treatment of select diseases and expect to nominate our third development candidate in 2024. Our goal is to utilize our capabilities and our FUSIONTM System platform to become the leader in developing covalent small molecules to maximize the depth and durability of clinical benefit when treating various diseases.

After working closely together at Pharmacyclics, our Chief Executive Officer and Chairman of the Board of Directors, Thomas Butler, and Chief Operating Officer and President, Ramses Erdtmann, founded Biomea Fusion in 2017 with the

shared vision and goal of developing targeted therapies for patients suffering from genetically defined cancers and metabolic diseases. Today, Biomea has grown to over 100 employees, and has built a management team with significant experience both in precision medicine and in progressing products from early-stage research to clinical trials and ultimately to regulatory approval and commercialization. Biomea has 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 management team have held various positions at several renowned biotechnology companies including, Gilead, and Genentech, Pharmacyclics, AbbVie, Celera, and others, and includes the co-inventors of covalent inhibitors Imbruvica, Remdesivir, and Harvoni. We are supported by our board of directors, scientific advisory board, and a leading syndicate of investors.

Our Programs

We are a clinical-stage biopharmaceutical company dedicated to discovering and developing oral covalent small molecules to treat and improve the lives of patients with metabolic diseases and genetically defined cancers. Leveraging our extensive expertise in covalent binding chemistry and development, we built our proprietary FUSIONTM System discovery platform to advance a pipeline of novel covalent small molecule product candidates. Our goal is to utilize our capabilities and FUSIONTM System to become the leader in developing covalent small molecules to maximize the depth and durability of clinical benefit when treating various diseases. To date we have announced two clinical development candidates, BMF-219 and BMF-500. The following table summarizes our wholly-owned research and development pipeline:

Our current pipeline and potentially addressable patient population

BMF-219

Our lead product candidate, BMF-219, 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 BMF-219 for the treatment of menin regulated or dependent diseases such as type 1 and type 2 diabetes as well as subtypes of liquid and solid tumors.

BMF-219 in Diabetes

We are currently investigating BMF-219 in diabetes in our ongoing Phase 1/2 clinical trial COVALENT-111 (patients with type 2 diabetes) and our ongoing Phase 2 clinical trial COVALENT-112 (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 (mediated by autoimmune dysfunction) and type 2 diabetes (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, 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 inhibition of menin could lead to the regeneration 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.

In October 2022, we announced completion of the Phase 1 portion of COVALENT-111, a Phase 1/2 clinical trial of BMF-219 in healthy volunteers and adults with type 2 diabetes in Canada. In December 2022, we announced FDA clearance of the IND for BMF-219 in type 2 diabetes, allowing us to expand the COVALENT-111 study to sites in the United States. In January 2023, we announced the dosing of the first patient with type 2 diabetes in the United States.

In March 2023, we reported initial clinical data from the Phase 2 portion of COVALENT-111. 40 patients were enrolled in the first three cohorts of COVALENT-111, with the first cohort (Cohort 1) comprising 16 healthy volunteers (HVs); 12 HVs were exposed to 100 mg BMF-219 once daily (QD) for two weeks and four HVs were exposed to placebo. In Cohorts 2 and 3, type 2 diabetes patients (n=12 per cohort of which 10 subjects were treated with BMF-219 and two subjects treated with placebo instead) received BMF-219 or placebo once daily for four weeks with or without food, respectively. In the two active treatment cohorts, enrolled patients had type 2 diabetes diagnosed for ≤ 15 years, were between the ages of 18 to 65, had been treated with lifestyle management together with up to three anti-diabetic medications, with a stable dose for at least two months prior to screening, had a BMI ≥25 and ≤40 kg/m2, and had poorly controlled diabetes (HbA1c ≥7.0% and ≤10%). At baseline, diabetic patients enrolled in the two treatment cohorts, Cohorts 2 and 3, had a median A1c of 7.9% and 7.8%, respectively.

Treatment Cohort 3 (BMF-219 without food) compared to Cohort 2 (BMF-219 with food) showed a positive dose-response pharmacokinetics relationship demonstrated by about a threefold median increase in Cmax (ng/ml) and AUC (ng x h/ml) when BMF-219 was administered without food. This increase in BMF-219 systemic exposure was in line with the differences seen in the response rates between the two cohorts. Specifically, the change in HbA1c at four weeks for Cohort 3 patients (n=9) (the denominator in Cohort 3 is 9 because the week 4 sample for one patient was unable to be processed) on BMF-219 (100 mg, without food) showed a median A1c reduction of -1.0% and a 89% (8/9) response rate at four weeks, with 78% of subjects achieving a ≥0.5% reduction in A1c and 56% achieving a ≥1.0% reduction in A1c. Cohort 2 patients (n=10) on BMF-219 (100 mg, with food) showed a median A1c reduction of -0.3% and a 70% (7/10) response rate at 4 weeks, with 30% of subjects achieving a ≥0.5% to ≤1.0% reduction in A1c. Subjects on placebo (n=4) showed a median and mean A1c reduction between -0.1% and -0.15%.

We also reported data from Cohorts 1, 2, and 3 of COVALENT-111. BMF-219 was generally well tolerated; all patients completed the four-week treatment, and completed follow-up to assess the durability of the treatment effect. There were no dose reductions, serious AEs, or severe AEs. In the active treatment Cohorts 2 and 3 (100 mg QD, n=24) 7 of 20 patients treated with BMF-219 showed mild (Grade 1) Treatment Emergent AEs (TEAEs), 1 of 20 patients treated with BMF-219 showed a moderate (Grade 2) TEAE and 2 of 4 subjects treated with placebo showed mild (Grade 1) TEAEs. No subjects showed symptomatic hypoglycemia and no other TEAEs were observed. In the healthy volunteer (HV) Cohort 1 (100 mg QD, n=16), 2 of 12 subjects treated with BMF-219 and 1 of 4 subjects treated with placebo showed mild (Grade 1) TEAEs. No other TEAEs were observed.

In June 2023, we presented additional clinical data from the first two cohorts of patients with type 2 diabetes enrolled in the Phase 2 portion of COVALENT-111. At Week 12, eight weeks after the last dose of BMF-219, patients who received BMF-219 in Cohort 2 and 3 had a mean HbA1c reduction of 0.1% and 1.0%, respectively. Specifically in Cohort 3 (100 mg BMF-219 QD without food for 4 weeks), 50% of patients (n=5/10) saw a continued improvement in HbA1c with a mean reduction in HbA1c of 1.49% at Week 12, compared to the mean reduction of 0.9% at the end of the dosing period at Week 4 (an additional 62% HbA1c reduction). 60% (n=6/10) of Cohort 3 patients achieved an HbA1c of 7% or below at the end of Week 12, compared to 30% (n=3/10) at the end of dosing period (Week 4) and 10% (n=1/10) at the end of Week 1. The average C-peptide expression for patients in Cohort 3 increased through Week 8. A similar increase in HOMA-B was observed, stabilizing at Week 8. As measured by continuous glucose monitoring (CGM), 7 of 10 (70%) patients maintained or improved time in range while off treatment (between Week 4 and Week 12). As measured by CGM, 60% (n=6/10) of Cohort 2 patients maintained or improved time in range while off treatment (between Week 4 and Week 12). Subjects on placebo (n=4) in Cohorts 2 and 3 showed a mean HbA1c increase of 0.10% at Week 12. HVs in Cohort 1, did not show a meaningful change (-0.1% to 0.1%) in HbA1c during 14 days of BMF-219 treatment and 6 weeks of follow-up.

Tolerability data during the off-treatment period was also presented. During the Week 4 to Week 12 off-treatment period, no severe or serious TEAEs were noted. Dosing of patients in the 200 mg without food cohort was recently completed and is now in the follow-up period. The 200 mg with food cohort led to an increase in mild to moderate nausea compared to 200 mg without food. This cohort will be transitioned to 100 mg BID dosing. No other clinical symptoms or clinical concerns were observed in this dose level.

In September 2023, we announced FDA and Health Canada clearance of the expansion cohorts of the ongoing Phase 2 clinical trial (COVALENT-111) in type 2 diabetes mellitus, allowing us to evaluate BMF-219, administered at 100 mg and 200 mg, with dosing durations up to 12 weeks in type 2 diabetes patients. The expansion portion will consist of approximately 300 patients with 54 subjects treated with BMF-219 and 18 treated with placebo in each arm. We also provided a high-level update on a total of 32 type 2 diabetes mellitus patients dosed for four weeks at 100 or 200 mg to date (10 active patients per arm, with dose levels 100 mg with food, 100 mg without (w/o) food, 200 mg w/o food, and 200 mg with food (n=2)). Compared to baseline, 84% of all patients dosed for four weeks with BMF-219 (n=32) in the escalation portion of COVALENT-111 showed a reduction in HbA1c at Week 4 and 74% at Week 12, two months after the final dose of BMF-219. During the 4-week dosing period, BMF-219 was generally well tolerated; there were no dose reductions, dose discontinuations, or severe or serious AEs. Also, during the off-treatment period (Week 4 to Week 12), no severe or serious TEAEs were noted.

In October 2023, we announced FDA clearance of the IND for BMF-219 in type 1 diabetes mellitus, allowing us to initiate a Phase 2 clinical trial in approximately 150 patients with stage 3 type 1 diabetes (COVALENT-112) at two oral dose levels (50 subjects treated with BMF-219 and 25 treated with placebo for each dose level), 100 mg and 200 mg unfed, for 12-weeks of treatment followed by a 40 week off-treatment period. The trial will also include an open label portion (n=40), enrolling participants in the U.S. and Canada with type 1 diabetes up to 15 years since diagnosis. In December 2023, we announced Health Canada clearance of Clinical Trial Application (CTA) for BMF-219 in type 1 diabetes.

In December 2023, we also presented long-term follow-up data showing improved glycemic control after 22 weeks off treatment in the ongoing Phase 2 study (COVALENT-111) of BMF-219 in type 2 diabetes. At Week 26, 22 weeks after the last dose of BMF-219, participants in the 100 mg QD (without food) cohort saw an improved placebo adjusted mean reduction in HbA1c of 0.8% (compared to a 0.7% placebo adjusted mean reduction in HbA1c at Week 4). Observed HbA1C reduction was supported by an increase from baseline in placebo adjusted mean HOMA-B (+270%) and in mean stimulated C-peptide AUC (+22%) at Week 26 in responders (defined as HbA1c reduction ≥0.5% at Week 26) with baseline below the HOMA-B upper limit of normal (<200). BMF-219 was generally well tolerated; no dose reductions, dose discontinuations, or severe or serious AEs and no symptomatic or asymptomatic hypoglycemia was observed. In addition, we reported that the 200 mg cohorts near doubled the percentage of patients (36%) with durable HbA1c reduction of 1% or more compared to the 100 mg cohorts which reported earlier as 20%.

In January 2024, we announced the dosing of the first type 1 diabetes patient in our Phase 2 study (COVALENT-112) with BMF-219. Initial proof of concept clinical data in type 1 diabetes patients is expected in 2024.

BMF-219 in Oncology

We are currently investigating BMF-219 in oncology in our ongoing Phase 1 clinical trial COVALENT-101 (patients with subtypes of leukemia and lymphoma) and our ongoing Phase 1/1b clinical trial COVALENT-102 (patients with KRAS solid tumors).

In January 2022, we announced that we had initiated dosing in COVALENT-101, a Phase 1 clinical trial to explore the safety and efficacy of BMF-219 in patients with relapsed/refractory AML and acute lymphoblastic leukemia (ALL), including those with MLL/KMT2A gene arrangements or NPM1 mutations. In 2022, we amended the IND to initiate additional cohorts in the COVALENT-101 study to explore the potential utility of BMF-219 across a range of menin-dependent hematologic malignancies including MM, DLBCL, and CLL.

In October 2022, we announced the initiation of a Phase 1/1b clinical trial of BMF-219 (COVALENT-102) in patients with unresectable, locally advanced, or metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and pancreatic

ductal adenocarcinoma (PDAC) with an activating KRAS mutation. Dose escalation completion and selection of the recommended Phase 2 dose are expected in 2024.

In July 2023, we also reported initial topline data from ongoing Phase 1 clinical trial (COVALENT-101) showcasing initial responses in relapsed/refractory AML patients with menin-dependent mutations. New data revealed two Complete Responses (CRs) (1 CR, 1 CRi) out of five relapsed/refractory AML patients carrying menin-dependent mutations treated at Dose Level 4. BMF-219, the first and only investigational covalent small-molecule menin inhibitor in clinical development to our knowledge, was generally well tolerated with no dose-limiting toxicities observed, and no QTc prolongation reported. Dose Level 4 exposure correlates with initial activity seen in BMF-219’s preclinical studies. We believe that this data supports further dose escalation.

In December 2023, we reported the achievement of minimal residual disease negativity (MRD-neg) in first complete responder in a patient with AML. Within the total of 7 patients selected as evaluable for efficacy, 2 CRs were observed with a mean time to response of 1.8 months. We believe that pharmacodynamic data from a case study of an AML patient containing NUP98-NSD1 mutation further supports the proposed mechanism of action of BMF-219 as a menin inhibitor; in-line with preclinical models, BMF-219 downregulated key leukemogenic genes (e.g. HOXA9, MEIS1) as well as MEN1. BMF-219 was generally well tolerated with no dose-limiting toxicities observed and without adverse event (AE) related treatment discontinuations. Four participants experienced Differentiation Syndrome (DS) ≤ Grade 3, managed by cytoreductive therapy (hydroxyurea and steroids). Two participants recovered without dose modification or interruption, and none of the participants discontinued due to DS. Clinical data to date support protocol enhancements to COVALENT-101 to include focusing exclusively on patients with menin sensitive mutations such as MLL-r and NPM1 mutant acute leukemias and higher dose levels for CYP3A4 inhibitor Arm (Arm B). Dose escalation completion and selection of the recommended Phase 2 dose are expected in 2024.

BMF-500

Including the discovery and development of BMF-219, we are utilizing our novel FUSIONTM System to pioneer covalent treatments against other high-value genetic drivers of disease. In May 2022, we announced the nomination of our second development candidate, BMF-500, a third-generation covalent inhibitor of activating mutations of the FMS-like tyrosine kinase 3 (FLT3), which are the most frequent genetic alteration in AML and are associated with poor prognosis. In December 2022, we presented initial preclinical data at the American Society of Hematology Annual Meeting (ASH) demonstrating BMF-500’s picomolar affinity to activating FLT3 mutations including FLT3-ITD and various tyrosine kinase domain (TKD) mutations, multi-fold higher potency and increased cytotoxicity than commercially available non-covalent FLT3 inhibitor gilteritinib, as well as complete tumor regression in mouse models of FLT3-ITD acute myeloid leukemia (AML) and maintenance of effect without continued exposure. In May 2023, we announced FDA clearance of our IND to study BMF-500 in a Phase 1 study (COVALENT-103) examining safety and efficacy in patients with relapsed or refractory acute leukemia with FLT3 wild-type and FLT3 mutations, including those with MLLr/NPM1 mutations. In October 2023, we announced the first patient has been dosed with BMF-500 in relapsed or refractory acute leukemia. Dose escalation completion and selection of the recommended Phase 2 dose are expected in 2024.

Our Strategy – We Aim to Cure

Biomea’s strategy is to identify key cellular regulators of homeostasis and molecular drivers of pathophysiological states, then to design, optimize, and develop covalent inhibitors that have the potential to produce clinically differentiated therapeutic profiles with an aim to cure. In cancer, mutations to key molecular pathways can constitutively hijack cell cycle machinery and disrupt pathways that results in abnormal or uncontrolled cell growth and division. We seek to recognize the clinical value of precision targeting of malfunctioning proteins through optimized covalent inhibition.

Our goal is to become a leader in the discovery, development and commercialization of highly selective, oral covalent therapies focused on metabolic diseases and cancer indications. Our scientists, with extensive backgrounds in structure-driven drug discovery and development, have taken aim at these molecular targets using covalent inhibition techniques. Specifically, we select highly sought-after targets that have been difficult to inhibit using conventional small molecule techniques. These conventional reversible drugs and drug candidates rely exclusively on keeping drug exposure in the patient’s bloodstream at a sufficiently high levels to continuously inhibit the therapeutic targets, often requiring a constant drug exposure to drive a clinical effect. The patient is thus subject to continuous systemic drug exposure during the course of treatment, which can lead to side effects caused by the drug’s off-target activity therefore disrupting normal homeostatic function.

Guided by the FUSIONTM system modeling, we design covalent small molecule drug candidates to work in a two-step process. First, an inhibitor reversibly associates with the target protein, where the chemical warhead of our covalent inhibitor comes within a close proximity of a targeted reactive amino acid residue of the target protein. In the second step, a bond is formed between the two reactive components in the inhibitor and the target protein, respectively, to form an irreversible covalent bond. 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. In contrast, the conventional reversible small molecule drug candidate may result in binding to multiple targets, which can lead to poor selectivity and cause unintended side effects. We believe this approach affords an added degree of selectivity, since “innocent” targets are not exposed to the drug for any longer than necessary.

With a wealth of experience in delivering versatile, approaches prior to joining Biomea including covalent inhibitor drugs such as IMBRUVICA (ibrutinib), we believe our team is uniquely positioned to leverage this knowledge in a wide variety of unmet medical needs.

Biomea aims to combine expertise in biology, chemistry, and medicine to create a suite of novel agents to improve and extend life for patients

The key elements of our business strategy include:

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Deploy our covalent platform against high-value oncogenic drivers of cancer. Leveraging our extensive experience developing covalent drugs and our structural biology and covalent binding chemistry expertise, we built our proprietary FUSIONTM System to design and develop a pipeline of novel covalent small molecule product candidates. We believe covalent binders offer a number of potential advantages over conventional reversible drugs, including greater target selectivity and the ability to drive deeper, more durable responses with lower drug exposure. Our goal is to utilize our capabilities and platform to become a leader in developing covalent drugs.

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Continue toadvance our lead product candidate, BMF-219, through clinical development. BMF-219 is a covalent menin inhibitor being developed for the treatment of diabetes and cancers that are highly dependent on menin. In January 2022, we announced that we had dosed the first patient in our first-in-human Phase 1 clinical trial of BMF-219 (COVALENT-101) in patients with relapsed or refractory acute leukemia and have subsequently expanded the trial to enroll cohorts of patients with other relapsed/refractory liquid tumors. We are also studying

BMF-219 across a range of menin dependent solid tumors in the ongoing Phase 1 COVALENT-102 clinical trial. Beyond cancer, we are exploring the potential of BMF-219, to treat type 2 diabetes in the ongoing Phase 1/2 COVALENT-111 trial as well as to treat type 1 diabetes in the ongoing Phase 2 COVALENT-112 trial.

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Continue to expand our portfolio of covalent small molecule product candidates. In addition to BMF-219, we are advancing two other preclinical covalent programs for the treatment of select cancers and announced our second development candidate, BMF-500, a covalent FLT3 inhibitor in May 2022. We expect to nominate our third development candidate in 2024. Both of these preclinical programs target clinically validated mechanisms of action and are complementary to the menin pathway.

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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 cancers 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 genetically defined cancers and 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 potential 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 ibrutinib, a number of 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 MM 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.

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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.

At Biomea, 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.

Our 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 oncogenic drivers of cancer. 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 FUSIONTM System leverages AI/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 cancers and metabolic diseases.

Our Initial Focus: Menin

Menin & Beta-Cell Biology in Diabetes

Diabetes is considered a chronic health condition that affects how the body turns food into energy and results in too much sugar in the bloodstream. Over time, this can cause serious health problems and damage vital organs. Most people with diabetes have a shorter life expectancy than people without this disease. Diabetes is one of the largest economic burdens on the U.S. health care system and the 7th leading cause of death in the U.S. According to the CDC, worldwide 537 million adults have diabetes. The CDC estimates about 2 in 5 of the adult population in the U.S. are now expected to develop diabetes during their lifetime. More than 37 million people of all ages (about 11% of the U.S. population) have diabetes today. 96 million adults (more than 1 in 3) have pre-diabetes, blood sugars that are higher than normal but not high enough to be classified as diabetes. Diabetes is also one of the largest economic burdens on the United States health care system with $1 out of every $4 in U.S. health care costs being spent on caring for people with diabetes. Despite the current availability of many diabetes medications, there remains a significant need in the treatment and care of patients with diabetes.

Diabetes is grouped into a few clinical categories based on etiology or timing of diagnosis according to the latest guidance from the American Diabetes Association (ADA). Accounting for 1.6 million diagnosed patients in the U.S., type 1 diabetes is due to autoimmune beta cell destruction, usually leading to absolute insulin deficiency, including latent autoimmune diabetes of adulthood. Type 2 diabetes has been diagnosed in approximately 25.3 million people in the U.S. and is due to a progressive loss of adequate beta cell insulin secretion frequently on the background of insulin resistance. The primary treatment goal is to achieve glycemic control by reducing HbA1c (A1c), a marker for the amount of sugar in the bloodstream, to 6.5% or lower. Glycemic control is a validated approach to delaying disease progression, which leads to significant and potentially fatal renal, cardiac, neurological, and ophthalmic comorbidities.

Loss of functional beta cell mass is a core component of the natural history in both types of diabetes — type 1 diabetes (mediated by autoimmune dysfunction) and type 2 diabetes (mediated by metabolic dysfunction). Beta cells are found in the pancreas and are responsible for the synthesis and secretion of insulin. Insulin is a hormone that helps the body use glucose for energy and helps control blood glucose levels. In patients with diabetes, beta cell mass and function are diminished, 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 inhibition of menin could lead to the regeneration of normal healthy beta cells. Based on these and other scientific findings, Biomea is exploring the potential for BMF-219-mediated menin inhibition as a therapeutic approach to potentially halt or reverse progression of type 2 diabetes.

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

BMF-219 – Clinical Development in Diabetes

In October 2022, we announced the completion of the Phase 1 portion of COVALENT-111 in healthy volunteers in Canada and the dosing of the first patient with type 2 diabetes in the Phase 2 portion of COVALENT-111, also in Canada. In the

completed Phase 1 portion of the trial, healthy subjects were enrolled in single ascending dose cohorts to ensure safety at the prospective dosing levels for type 2 diabetic patients. BMF-219 was well tolerated and showed a favorable PK and PD profile.

In December 2022, we announced the clearance of the IND by the FDA for BMF-219 in type 2 diabetes to support the expansion of COVALENT-111 to sites in the U.S. The ongoing Phase 2 portion consists of multiple ascending dose cohorts and includes adult patients with type 2 diabetes uncontrolled by current therapies. It is designed to examine the capacity of BMF-219 to enable the proliferation, preservation, and reactivation of healthy, functional beta cells capable of producing insulin, thereby leading to long-term glycemic control. In January 2023, we announced the dosing of the first patient with type 2 diabetes in the United States.

On March 28, 2023, we reported topline initial clinical data from the Phase 2 portion of COVALENT-111. 40 subjects were enrolled in the first three cohorts of COVALENT-111, with the first cohort comprising 16 healthy volunteers (HVs); 12 HVs were exposed to 100 mg BMF-219 once daily for two weeks and four HVs were exposed to placebo. In Cohorts 2 and 3, type 2 diabetes mellitus patients (n=12 per cohort with 10 subjects treated with BMF-219 and 2 subjects on placebo) received BMF-219 once daily for four weeks with or without food, respectively. In the two active treatment cohorts, enrolled patients had type 2 diabetes mellitus diagnosed for ≤15 years, were ages 18 to 65, had been treated with lifestyle management together with up to three anti-diabetic medications, with a stable dose for at least two months prior to screening, had a BMI ≥25 and ≤40 kg/m2, and had poorly controlled diabetes with HbA1c ≥7.0% and ≤10%. At baseline, patients enrolled in the two active treatment cohorts, Cohorts 2 and 3 had a median A1c of 7.9% and 7.8%, respectively.

Observed HbA1c lowering of BMF-219

Active treatment Cohort 3 (BMF-219 without food) compared to Cohort 2 (BMF-219 with food) showed a positive dose-response pharmacokinetics relationship demonstrated by about a threefold median increase in Cmax(ng/ml) and AUC (ng x h/ml) when BMF-219 was administered without food. This increase in BMF-219 systemic exposure was in line with the differences seen in the response rates between the two cohorts. Specifically, the change in HbA1c at four weeks for Cohort 3 patients (n=9) on BMF-219 (100 mg, without food) showed a median A1c reduction of -1.0% and a 89% (8/9) response rate at four weeks, with 78% of subjects achieving a ≥0.5% reduction in A1c and 56% achieving a ≥1.0% reduction in A1c. Cohort 2 patients (n=10) on BMF-219 (100 mg, with food) showed a median A1c reduction of -0.3% and a 70% (7/10) response rate at four weeks, with 30% of subjects achieving a ≥0.5% to ≤1.0% reduction in A1c. Placebo patients (n=4) showed a median and mean A1c reduction between -0.1% and -0.15%.

We also reported on the tolerability profile of BMF-219 observed in Cohorts 1, 2, and 3 of COVALENT-111. BMF-219 was generally well tolerated; all patients completed the four-week treatment, and all patients continue in follow-up to assess the

durability of the treatment effect. There were no dose reductions, serious AEs, or severe AEs. In the active treatment Cohorts 2 and 3 (100 mg QD, n=24) 7 of 20 patients treated with BMF-219 showed mild (Grade 1) Treatment Emergent AEs (TEAEs), 1 of 20 patients treated with BMF-219 showed a moderate (Grade 2) TEAE and 2 of 4 patients treated with placebo showed mild (Grade 1) TEAEs. No patients showed symptomatic hypoglycemia and no other TEAEs were observed. In the healthy volunteer (HV) Cohort 1 (100 mg QD, n=16), 2 of 12 subjects treated with BMF-219 and 1 of 4 subjects treated with placebo showed mild (Grade 1) TEAEs. No other TEAEs were observed.

BMF-219 was generally well tolerated in patients enrolled in COVALENT-111

In June 2023, we presented additional clinical data from the first two cohorts of patients with type 2 diabetes enrolled in the Phase 2 portion of COVALENT-111. At Week 12, eight weeks after the last dose of BMF-219, patients who received BMF-219 in Cohort 2 and 3 had a mean HbA1c reduction of 0.1% and 1.0%, respectively. Specifically in Cohort 3 (100 mg BMF-219 QD without food for 4 weeks), 50% of patients (n=5/10) saw a continued improvement in HbA1c with a mean reduction in HbA1c of 1.49% at Week 12, compared to the mean reduction of 0.9% at the end of the dosing period at Week 4 (an additional 62% HbA1c reduction). 60% (n=6/10) of Cohort 3 patients achieved an HbA1c of 7% or below at the end of Week 12, compared to 30% (n=3/10) at the end of dosing period (Week 4) and 10% (n=1/10) at the end of Week 1. The average C-peptide expression for patients in Cohort 3 increased through Week 8. A similar increase in HOMA-B was observed, stabilizing at Week 8. As measured by continuous glucose monitoring (CGM), 7 of 10 (70%) of patients maintained or improved time in range while off treatment (between Week 4 and Week 12). As measured by CGM, 60% (n=6/10) of Cohort 2 patients maintained or improved time in range while off treatment (between Week 4 and Week 12). Placebo patients (n=4) in Cohorts 2 and 3 showed a mean HbA1c increase of 0.10% at Week 12. HVs in Cohort 1 showed minimal mean change (-0.1% to 0.1%) in HbA1c during 14 days of BMF-219 treatment and six weeks of follow-up.

The top 50% of responders after 4-weeks of treatment in Cohorts 2 and 3 demonstrated durable and ongoing reduction in HbA1c while off treatment up to Week 12; a continued reduction in HbA1c was observed in Cohort 2 (additional 114%) and in Cohort 3 (additional 62%), as presented at 2023 ADA, “COVALENT-111, A Phase 1/2 Trial of BMF-219, an Oral Covalent Menin Inhibitor, in Patients with Type 2 Diabetes Mellitus – Preliminary Results” (2023-LB-5598).

After 4-weeks of BMF-219 once daily dosing both cohorts demonstrated an increasing proportion of patients achieving a target HbA1c ≤ 7% and maintained through Week 12, as presented at 2023 ADA, “COVALENT-111, A Phase 1/2 Trial of BMF-219, an Oral Covalent Menin Inhibitor, in Patients with Type 2 Diabetes Mellitus – Preliminary Results” (2023-LB-5598)

Tolerability data during the off-treatment period was also presented. During the Week 4 to Week 12 off-treatment period, no severe or serious TEAEs were noted.

In September 2023, we announced FDA and Health Canada clearance of the expansion cohorts of the ongoing Phase 2 clinical trial (COVALENT-111) in type 2 diabetes mellitus, allowing us to evaluate BMF-219, administered at 100 mg and 200 mg, with dosing durations up to 12 weeks in type 2 diabetes mellitus patients. The expansion portion will consist of approximately 300 patients. We also provided a high-level update on a total of 32 type 2 diabetes mellitus patients dosed for four weeks at 100 or 200 mg to date (10 active patients per arm, with dose levels 100 mg with food, 100 mg without (w/o) food, 200 mg w/o food, and 200 mg with food (n=2)). Compared to baseline, 84% of all patients dosed for four weeks with BMF-219 (n=32) in the escalation portion of COVALENT-111 showed a reduction in HbA1c at Week 4 and 74% at Week 12, two months after the final dose of BMF-219. During the 4-week dosing period, BMF-219 was generally well tolerated;

there were no dose reductions, dose discontinuations, or severe or serious AEs. Also, during the off-treatment period (Week 4 to Week 12), no severe or serious TEAEs were noted.

COVALENT-111 trial design of dose escalation and dose expansion portion

In October 2023, we announced FDA clearance of the IND for BMF-219 in type 1 diabetes mellitus, allowing us to initiate a Phase 2 clinical trial in approximately 150 patients with stage 3 type 1 diabetes (COVALENT-112) at two oral dose levels, 100 mg and 200 mg unfed, for 12-weeks of treatment followed by a 40 week off-treatment period. In December 2023, we announced Health Canada clearance of Clinical Trial Application (CTA) for BMF-219 in type 1 diabetes. The trial will also include an open label portion (n=40), enrolling participants in the U.S. and Canada with type 1 diabetes up to 15 years since diagnosis.

In December 2023, we presented long-term follow-up data showing improved glycemic control after 22 weeks off treatment in ongoing Phase 2 study (COVALENT-111) of BMF-219 in type 2 diabetes. At Week 26, 22 weeks after the last dose of BMF-219, participants in the 100 mg QD (without food) cohort saw an improved placebo adjusted mean reduction in HbA1c of 0.8% (compared to a 0.7% placebo adjusted mean reduction in HbA1c at Week 4). Observed HbA1C reduction was supported by an increase from baseline in placebo adjusted mean HOMA-B (+270%) and in mean stimulated C-peptide AUC (+22%) at Week 26 in responders (defined as HbA1c reduction ≥0.5% at Week 26) with baseline below the HOMA-B upper limit of normal (<200). BMF-219 was generally well tolerated; no dose reductions, dose discontinuations, or severe or serious AEs and no symptomatic or asymptomatic hypoglycemia was observed. In addition, we reported that the 200 mg cohorts near doubled the percentage of patients (~36%) with durable HbA1c reduction of 1% or more compared to the 100 mg cohorts which reported earlier as 20%.

% increase in HOMA-B and C-peptide AUC in responders as presented at 2023 WCIRDC, “BMF-219: A Novel Therapeutic Agent to Re-Establish Functional Beta Cells and Provide Long-Term Glycemic Control”

A case study of a 29-year-old man with 4-year history of type 2 diabetes as presented at 2023 WCIRDC, “BMF-219: A Novel Therapeutic Agent to Re-Establish Functional Beta Cells and Provide Long-Term Glycemic Control”

In December 2023, we also presented preclinical ex-vivo human islet data. Dependent on dose concentration and also dependent on dose duration, BMF-219 was observed to increase beta cell mass and function, as well as promote controlled proliferation and enhance insulin content in beta cells. Proliferation was observed only under elevated glucose conditions, which mimics diabetic levels, and with continuous drug exposure. BMF-219 was observed to upregulate the expression of key cell-cycle proteins, PbK and CCNA2 (Cyclin A2) in a glucose-dependent fashion. When not sequestered to menin, PbK expression was known to be upregulated by JunD, which is a glucose-sensitive menin binding partner.

BMF-219 Induced a Glucose-Dependent Enhancement in β-Cell Proliferation as presented at 2023 WCIRDC, “BMF-219: A Novel Therapeutic Agent to Re-Establish Functional Beta Cells and Provide Long-Term Glycemic Control”

In January 2024, we announced the dosing of first type 1 diabetes patient in our Phase 2 study (COVALENT-112) with BMF-219. Initial proof of concept clinical data in type 1 diabetes patients is expected in 2024.

In March 2024, we presented additional clinical data sets from the dose escalation phase of COVALENT-111 which we believe support BMF-219’s novel proposed mechanism of action in patients with Type 2 Diabetes. As of the data cut-off of February 12, 2024, patients in COVALENT-111 are displaying improved glycemic control while off therapy, supporting improved pancreatic function following BMF-219 treatment. Patients who demonstrated the greatest HbA1c reduction at Week 26 (22 weeks off treatment) had the greatest improvement in beta cell function as measured by HOMA-B and C-peptide. In patients poorly controlled with current standard of care medications, at Week 26, following a 28 day dose cycle of BMF-219, a general dose response was observed with placebo adjusted mean percent changes of HbA1c of -0.04% (50mg QD*), -0.2% (100mg QD with food), -0.8% (100mg), -0.4% (200mg QD), -0.4% (100mg BID), and -1.4% (200mg with food) (*50mg data out to Week 20, latest data cut). Across 100mg QD, 200mg QD, and 100mg BID cohorts (N=40), 38% of patients had ≥0.5% HbA1c reduction (with a mean HbA1c reduction of 1.2%), and 23% of patients had ≥1.0% HbA1c reduction (with a mean HbA1c reduction of 1.5%) at Week 26. Patients with >7 years duration of diabetes and poorly controlled with dual- or triple-agent therapy (including GLP1 RA and/or SGLT2i) (n=2) also demonstrated improved glycemic control (HbA1c -0.4%, -1.1%, and -1.1% at Weeks 4, 12, and 26, respectively) with BMF-219 dosed at 200mg with food. Increase in HOMA-B and C-peptide generally correlated with glycemic control, consistent with BMF-219's proposed core mechanism of action: beta-cell proliferation and improved beta-cell function. BMF-219 was generally well tolerated with no serious adverse events and no adverse event-related study discontinuations, and no symptomatic or clinically significant hypoglycemia. 100mg and 200mg dose levels have been selected for the first 3 Arms of the Expansion Phase, which will dose patients up to 12 weeks (compared to 4 weeks in the Escalation Phase) and extended follow-up to Week 52.

HOMA-B and C-peptide at Week 26 generally increased with magnitude of reduction in HbA1C and in patients with baseline HOMA-B <200 with BMF-219 200 mg once daily dosing for 4 weeks, as presented at 2024 AATD, “Durable Glycemic Control with BMF-219 During Off-Treatment Period at Week 26: A Phase 1/2 Trial of BMF-219 in Patients with Type 2 Diabetes (COVALENT-111)”

PK at Week 4 and Corresponding HbA1c Response at Week 26 as presented at 2024 AATD, “Key Observations from the Dose Escalation Portion of COVALENT-111, a Phase 1/2 Trial of the Covalent Menin Inhibitor BMF-219 in Patients with Type 2 Diabetes”

A case study of a patient with a 10-year history of T2D and on triple-agent regimen (metformin, GLP1 RA, and SGLT2i) at baseline, experienced a 1.1% reduction in HbA1c and an increase of 30% in TIR compared to baseline at Week 26, as presented at 2024 AATD, “Key Observations from the Dose Escalation Portion of COVALENT-111, a Phase 1/2 Trial of the Covalent Menin Inhibitor BMF-219 in Patients with Type 2 Diabetes”

BMF-219 – Clinical Development in Oncology

We are developing BMF-219 for the treatment of liquid and solid tumors that are highly dependent on menin, including leukemias containing the MLL fusion protein. In September 2021, we announced that the U.S. FDA had cleared our IND application to begin a Phase 1 trial of BMF-219 (COVALENT-101) in adult patients with R/R acute leukemia including those with an MLL/KMT2A (Mixed Lineage Leukemia/Lysine Methyl Transferase) gene rearrangement or nucleophosmin 1 (NPM1) mutation. In December 2021, we amended our IND to include subsets of MM and DLBCL patients. In January 2022, we announced the dosing of the first leukemia patient in our COVALENT-101 trial and in June 2022, we announced the dosing of the first patient in the MM cohort of COVALENT-101. In September 2022, we amended the IND to also include subsets of patients with chronic lymphocytic leukemia (CLL) and announced the dosing of the first patient in the CLL cohort in October 2022.

COVALENT-101 is an ongoing Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-219 in adult patients with R/R hematologic malignancies (NCT05153330). The study is enrolling four cohorts: AML/ALL (Cohort 1), DLBCL (Cohort 2), MM (Cohort 3) and CLL (Cohort 4).

COVALENT-101 trial design (NCT05153330)

In October 2022, we announced FDA clearance of the IND application for BMF-219 in KRAS mutant solid tumors and the initiation of a Phase 1/1b clinical trial (COVALENT-102). COVALENT-102 is examining BMF-219 as a monotherapy in patients who have unresectable, locally advanced, or metastatic NSCLC, CRC or PDAC with a KRAS mutation. A targeted pan-KRAS inhibitor has the potential to treat the estimated 25-35% of NSCLC, 35-45% of CRC, and approximately 90% of PDAC patients with a KRAS mutation. In January 2023, we announced the dosing of the first patient in the COVALENT-102 study.

COVALENT-101 trial design (NCT05153330)

In July 2023, we also reported initial topline data from an ongoing Phase 1 clinical trial (COVALENT-101) showcasing initial responses in relapsed/refractory AML patients with menin-dependent mutations. New data revealed 2 Complete Responses (CRs) (1 CR, 1 Cri) out of 5 relapsed/refractory AML patients carrying menin-dependent mutations treated at Dose Level 4. BMF-219 was generally well tolerated with no dose-limiting toxicities observed, and no QTc prolongation reported. Dose Level 4 exposure correlated with initial activity seen in BMF-219’s preclinical studies. We believe that the current safety profile of BMF-219 supports further dose escalation.

In December 2023, we reported the achievement of minimal residual disease negativity (MRD-neg) in the first complete responder in a patient with AML. Within the total of 7 patients selected as evaluable for efficacy, 2 CRs were observed with a

mean time to response of 1.8 months. In the CYP inhibitor arm, BMF-219 showed increasing plasma pharmacokinetic (PK) exposure with escalating dose levels, and the ability to achieve systemic exposures predicted to be clinically active based on preclinical acute leukemia models. We believe that pharmacodynamic data further supports the proposed mechanism of action of BMF-219 as a menin inhibitor; in-line with preclinical models, BMF-219 downregulated key leukemogenic genes (e.g. HOXA9, MEIS1) as well as MEN1. BMF-219 was generally well tolerated with no dose-limiting toxicities observed and without adverse event (AE) related treatment discontinuations. Four participants experienced Differentiation Syndrome (DS) ≤ Grade 3, managed by cytoreductive therapy (hydroxyurea and steroids). Two participants recovered without dose modification or interruption, and none of the participants discontinued due to DS. Clinical data to date support protocol enhancements to COVALENT-101 to include focusing exclusively on patients with menin sensitive mutations such as MLL-r and NPM1 mutant acute leukemias and higher dose levels for CYP3A4 inhibitor Arm (Arm B). Dose escalation completion and selection of the recommended Phase 2 dose are expected in 2024.

In the CYP inhibitor arm, BMF-219 showed increasing plasma pharmacokinetic (PK) exposure with escalating dose levels as presented at 2023 ASH, “Covalent Menin Inhibitor BMF-219 in participants with Relapsed or Refractory (R/R) Acute Leukemia (AL): Preliminary Phase 1 Data from the COVALENT-101 Study” (Abstract 2916)

Gene expression profiling in a patient with AML containing the NUP98-NSD1 fusion under treatment with covalent menin inhibitor BMF-219 as presented at 2023 ASH, “Covalent Menin Inhibitor BMF-219 in participants with Relapsed or Refractory (R/R) Acute Leukemia (AL): Preliminary Phase 1 Data from the COVALENT-101 Study” (Abstract 2916)

BMF-219 demonstrated early signs of clinical efficacy as presented at 2023 ASH, “Covalent Menin Inhibitor BMF-219 in participants with Relapsed or Refractory (R/R) Acute Leukemia (AL): Preliminary Phase 1 Data from the COVALENT-101 Study” (Abstract 2916)

BMF-219 was generally well-tolerated across all dose levels as presented at 2023 ASH, “Covalent Menin Inhibitor BMF-219 in participants with Relapsed or Refractory (R/R) Acute Leukemia (AL): Preliminary Phase 1 Data from the COVALENT-101 Study” (Abstract 2916)

Other Clinical and Preclinical Programs

Beyond BMF-219, we are utilizing our novel platform to develop covalent treatments against other high-value oncogenic drivers of cancer. In May 2022, we announced our second development candidate, BMF-500, a covalent inhibitor of FLT3. BMF-500 is being developed as a highly potent and selective, covalent, small molecule inhibitor of FLT3, that is designed to bind irreversibly to a reactive cysteine in the kinase active site.

BMF-500 is a third-generation covalent inhibitor of FLT3, which, in preclinical studies has demonstrated picomolar IC50 values across key FLT3 isoforms, potentially making it the most potent inhibitor of its class. Activating mutations of the FMS-like tyrosine kinase 3 (FLT3) are the most frequent genetic alteration in AML and are associated with poor prognosis. Though several FLT3 inhibitors have entered clinical trials and reached commercialization, adverse events and dose-limiting toxicities often restrict the therapeutic window and limit their long-term use. Such limitations can impact the ability to achieve long-lasting response in patients and ultimately result in therapy-induced resistance.

At the ASH Annual Meeting in December 2022, we presented preclinical data supporting the potential of BMF-500 as a highly potent and selective FLT3 inhibitor. The presentation described BMF-500’s picomolar affinity to activating FLT3 mutations including FLT3 internal tandem duplications (FLT3-ITD) and various tyrosine kinase domain (TKD) mutations, multi-fold higher potency and increased cytotoxicity than commercially available non-covalent FLT3 inhibitor gilteritinib, and complete tumor regression at physiologically relevant doses in mouse models of FLT3-ITD AML and maintenance of effect without continued exposure. BMF-500 selectively killed AML cells harboring FLT3 activating mutations, including MV4-11 and MOLM-13, and engineered cells expressing FLT3-ITD and/or FLT3 TKD mutations. In ex vivo cultures, BMF-500 as a single agent induced potent growth inhibition of patient-derived AML cells harboring either FLT3-ITD or FLT3 non-ITD mutations.

BMF-219 and BMF-500 in Combination Induced Higher Cell Killing at Lower Single Agent Concentrations as presented at 2023 AACR, “Combinatorial approach using covalent menin inhibitor, BMF-219, and/or covalent FLT3 inhibitor, BMF-500, with MEK or BCL2 blockade potentiates therapeutic use in AML” (Abstract 4939)

The potent covalent inhibition of FLT3 by BMF-500 manifested durable cellular response that was improved over gilteritinib. A three-hour exposure followed by wash-out of BMF-500 outperformed four days of continuous exposure to gilteritinib, at all concentrations tested. In cells harboring FLT3 activating mutations, BMF-500 induced dose-dependent inhibition of FLT3 phosphorylation and downstream signaling, including phospho-STAT5 and phospho-ERK. A 1-hour pulse treatment with BMF-500 was sufficient to achieve deep and durable target inhibition for greater than 24 hours, an effect not observed with gilteritinib under similar conditions.

Potent FLT3 inhibition and high selectivity of BMF-500 translated to sustained tumor regression and improved survival in both subcutaneous and disseminated xenograft models of mutant FLT3-driven AML. Orally administered BMF-500 was well tolerated over four weeks of dosing. We believe BMF-500 is a novel FLT3 inhibitor, given its activity, durability, and selectivity in comparison to existing FLT3 inhibitors.

Potent and durable target inhibition leading to active cell killing in comparison to gilteritinib as presented at the ASH Annual Meeting in 2022, “BMF-500: An Orally Bioavailable Covalent Inhibitor of FLT3 with High Selectivity and Potent Antileukemic Activity in FLT3-Mutated AML” (Abstract 2756)

Potent Cell-Based Activity in AML Cell Lines with FLT3 Mutations as presented at the ASH Annual Meeting in 2022, “BMF-500: An Orally Bioavailable Covalent Inhibitor of FLT3 with High Selectivity and Potent Antileukemic Activity in FLT3-Mutated AML” (Abstract 2756)

Potent coverage of FLT3 inhibitor resistant mutation as presented at the ASH Annual Meeting in 2022, “BMF-500: An Orally Bioavailable Covalent Inhibitor of FLT3 with High Selectivity and Potent Antileukemic Activity in FLT3-Mutated AML” (Abstract 2756)

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.

To our knowledge, there are several programs that target menin in clinical development for acute leukemias at this time; we are aware of Kura Oncology’s KO-539 and Syndax Pharmaceuticals’ SNDX-5613, both of which target the menin-MLL1 interaction through the use of non-covalent inhibition. Both KO-539 and SNDX-5613 are in clinical development and have demonstrated Phase 1 results that support continued development into pivotal studies and validate menin as a therapeutic target. Other clinical programs have been reported by Daiichi Sankyo (DS-1594), Janssen Pharmaceuticals (JNJ-75276617) and Sumitomo Pharma Oncology (DSP-5336). Additionally, other preclinical programs have been reported by Bayer (BAY-155), Novartis, and the University of Michigan.

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, plus the time between the submission date of a new drug application 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, 2023, 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 BMF-219 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 BMF-219, 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, 2023, 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. 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 New Drug Application (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 patients 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 patients. 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 1: The product candidate is initially introduced into healthy human subjects or patients 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 2: The product candidate is administered to a limited patient 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 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive Phase 3 clinical trials.

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Phase 3: The product candidate is administered to an expanded patient 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 4 studies may be conducted after initial marketing approval, and may be used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA.

In March 2022, the FDA released a final guidance entitled “Expansion Cohorts: Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics,” which outlines how drug developers can utilize an adaptive trial design commonly referred to as a seamless trial design in early stages of oncology drug development (i.e., the first-in-human clinical trial) to compress the traditional three phases of trials into one continuous trial called an expansion cohort trial. Information to support the design of individual expansion cohorts are included in IND applications and assessed by the FDA. Expansion cohort trials can potentially bring efficiency to drug development and reduce developmental costs and time.

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 nonclinical 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 2, 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 2 trial to discuss Phase 2 clinical results and present plans for the pivotal Phase 3 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 4 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 1 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 now 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.

With respect to oncology products, the FDA may review applications under Real-Time Oncology Review (RTOR) established by the FDA’s Oncology Center of Excellence. RTOR, which allows an applicant to pre-submit components of the application to allow the FDA to review clinical data before the complete filing is submitted, aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible, while maintaining and improving review quality. Drugs considered for review under RTOR must, among other things, be likely to demonstrate substantial improvements on a clinically relevant endpoint(s) over available therapy, and must have easily interpreted endpoints. In addition, no aspect of the application should be likely to require a longer review time, such as, for example, a requirement for a new REMS. To determine eligibility for RTOR, the FDA requires top-line efficacy and safety results from an applicant’s pivotal clinical trial(s), as well as completion of database lock for the clinical trial(s). The FDA will generally make a decision regarding acceptance into RTOR within twenty (20) business days of receipt of the request from the applicant. If an applicant is not accepted into RTOR, the applicant will follow routine application submission procedures.

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.

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 & 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, the Occupational Safety & 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 Federal Trade Commission (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 Federal Trade Commission 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 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 percent point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; and

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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. At a federal level, President Biden has issued multiple executive orders that have sought to reduce prescription drug costs. In February 2023, HHS also issued a proposal in response to an October 2022 executive order from President Biden that includes a proposed prescription drug pricing model that will test whether targeted Medicare payment adjustments will sufficiently incentivize manufacturers to complete confirmatory trials for drugs approved through FDA’s accelerated approval pathway. Although a number of these and other proposed measures may require authorization through additional legislation to become effective, and the Biden administration may reverse or otherwise change these measures, both the Biden administration and Congress have indicated that they will continue to seek new legislative 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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On August 2, 2011, the U.S. Budget Control Act of 2011, among other things, included aggregate reductions of Medicare payments to providers of 2% per fiscal year. These reductions went into effect on April 1, 2013 and, due to subsequent legislative amendments to the statute, will remain in effect until 2031.

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On January 2, 2013, 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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On April 13, 2017, CMS published a final rule that gives states greater flexibility in setting benchmarks for insurers in the individual and small group marketplaces, which may have the effect of relaxing the essential health benefits required under the ACA for plans sold through such marketplaces.

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On May 30, 2018, the Right to Try Act, was signed into law. The law, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase 1 clinical trial and that are undergoing investigation for FDA approval. Under certain circumstances, eligible patients can seek treatment without enrolling in clinical trials and without obtaining FDA permission under the FDA expanded access program. There is no obligation for a pharmaceutical manufacturer to make its drug products available to eligible patients as a result of the Right to Try Act.

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On May 23, 2019, CMS published a final rule to allow Medicare Advantage Plans the option of using step therapy for Part B drugs beginning January 1, 2020.

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On March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently 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 will be further reduced starting in 2025 absent further legislation.

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The IRA was signed into law in August 2022. The IRA 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, 2023, we had 103 full-time employees, 78 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

Biomea Fusion, Inc., (the “Company”), was 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.

BMEA US Equity

BMEA · 10-K · period ended 2023-12-31

Item 1. Business

BMEA US Equity☆

BMEA · 10-K · period ended 2023-12-31

Item 1. Business

BMEA US Equity