Core Insights - Biomea Fusion is transitioning to focus on diabetes and obesity medicines, with icovamenib as a cornerstone for metabolic disorders [1][10] - The company plans to present a corporate update at the 43rd Annual J.P. Morgan Healthcare Conference on January 15, 2025 [11] Clinical Development - Icovamenib is a potential first-in-class menin inhibitor showing a 1.5% mean reduction in HbA1c in severely insulin deficient patients [2] - In patients uncontrolled on GLP-1-based therapies, icovamenib achieved a 1.0% mean HbA1c reduction [3] - The drug demonstrated significant benefits in patients with the lowest insulin production, validating its mechanism of action [4] - Patients experienced continued HbA1c reductions for 14 weeks after a 12-week treatment period [5][10] - Icovamenib was well tolerated, with no reported adverse-event related discontinuations or serious adverse events [6] Patient Population - In a subgroup of severely insulin deficient patients, 100% responded to icovamenib, indicating a durable reduction in HbA1c [7] - This patient group represents approximately 20% of the type 2 diabetes population in the U.S. and Europe, characterized by high unmet medical needs [7] Mechanism and Future Plans - Preclinical studies suggest icovamenib enhances GLP-1-based therapies, improving glycemic control and beta cell function [8] - The company plans to conduct two clinical trials focusing on insulin deficient type 2 diabetes patients and those initiating GLP-1 therapy [9] - Biomea aims to engage with the FDA to support the development of icovamenib for these patient groups [8][10] Company Overview - Biomea Fusion is a clinical-stage biopharmaceutical company focused on developing oral covalent small molecules for diabetes, obesity, and genetically defined cancers [14] - The company utilizes its proprietary FUSION™ System to design next-generation covalent-binding small-molecule medicines [15]

Core Insights - Biomea Fusion is transitioning to focus on diabetes and obesity medicines, with icovamenib as a cornerstone for metabolic disorders [1][10] - The company plans to conclude studies on icovamenib's oncology potential and concentrate resources on metabolic disorders [1] Clinical Trial Results - Icovamenib demonstrated a placebo-adjusted mean reduction of 1.5% in HbA1c for severely insulin-deficient patients [2] - In patients suboptimally controlled on GLP-1 therapies, icovamenib showed a 1.0% mean HbA1c reduction [3] - The drug was well tolerated, with no reported adverse-event related discontinuations or serious adverse events [6] Patient Population - The severely insulin-deficient patient group represents about 20% of the type 2 diabetes population in the U.S. and Europe, characterized by low insulin production and high unmet medical needs [7] - All patients in the subgroup responded positively to icovamenib, showing durable HbA1c reductions even after treatment cessation [7] Mechanism of Action - Icovamenib is designed to regenerate insulin-producing beta cells, potentially serving as a disease-modifying therapy for diabetes [13] - Preclinical studies indicate that icovamenib enhances GLP-1 therapies, improving glycemic control and beta cell function [8] Future Plans - Biomea Fusion will present further results from the COVALENT-111 trial at an upcoming medical conference [7] - The company plans to engage with the FDA to support clinical trials for insulin-deficient patients and those on GLP-1 therapies [8][10] - Two clinical trials are planned: a Phase 2/3 trial for insulin-deficient type 2 diabetes and a Phase 2b trial for icovamenib in combination with GLP-1 therapies [9]

Core Viewpoint - Biomea Fusion, Inc. announced promising results from preclinical studies of icovamenib in combination with semaglutide, indicating potential advancements in diabetes treatment [1][5]. Study Overview - The preclinical study assessed the efficacy of icovamenib, a covalent menin inhibitor, combined with semaglutide, focusing on metabolic parameters in animal models [2]. - The study involved two groups of Zucker Diabetic Fatty (ZDF) rats, one receiving icovamenib and semaglutide, and the other receiving semaglutide alone [2]. Key Findings - **Superior Glycemic Control**: Combination therapy resulted in a greater than 1% reduction in HbA1c on Day 28 compared to semaglutide alone (p<0.05) [3]. - **Insulin Resistance and Beta Cell Function**: Insulin resistance (HOMA-IR) decreased by 75% with combination therapy compared to semaglutide alone (p<0.001) [7]. - **Weight Loss and Muscle Mass Improvements**: Combination therapy led to an 11.5% reduction in body weight and a 43% increase in lean muscle mass compared to semaglutide alone [5][7]. Additional Data - Icovamenib combined with semaglutide approximately doubled C-peptide production per unit of glucose, resulting in a 60% reduction in fasting blood glucose levels [5][6]. - A 50% reduction in area under the curve (AUC) during the Oral Glucose Tolerance Test (OGTT) was observed with combination therapy (p<0.0001) [6]. - Topline data from the COVALENT-111 study indicated a 0.84% reduction in HbA1c after 12 weeks of daily icovamenib in patients uncontrolled on GLP-1 therapy [5]. Safety and Tolerability - Icovamenib in combination with semaglutide was well tolerated across multiple time points [8]. Mechanism of Action - Icovamenib is designed to regenerate insulin-producing beta cells, potentially halting or reversing the progression of type 2 diabetes [11]. Industry Context - Diabetes is a significant health issue, with over 37 million people in the U.S. affected, and it represents a major economic burden on the healthcare system [10]. - There remains a substantial need for effective diabetes treatments despite the availability of current medications [10].

Company Overview - Biomea Fusion, Inc. is a clinical-stage biopharmaceutical company focused on discovering and developing oral covalent small molecules aimed at treating diabetes, obesity, and genetically defined cancers [1][3] - The company utilizes its proprietary FUSION™ System to design and develop a pipeline of next-generation covalent-binding small-molecule medicines [3] Upcoming Events - Thomas Butler, the CEO and Chairman of the Board, will present at the 43rd Annual J.P. Morgan Healthcare Conference on January 15, 2025, at 1:30 PM Pacific Time / 4:30 PM Eastern Time [1] - Biomea's management team will also host one-on-one meetings throughout the conference, which runs from January 13 to January 16, 2025 [1] Presentation Access - A live audio webcast of the presentation will be available on Biomea's website, with a replay accessible after the live event [2]

Core Insights - Biomea Fusion announced positive topline results from the COVALENT-111 study, demonstrating significant efficacy of icovamenib in reducing HbA1c levels in patients with type 2 diabetes [1][3][6] - Icovamenib showed a placebo-adjusted mean reduction of 1.47% in HbA1c at Week 26 for beta-cell deficient patients, indicating its potential as a novel treatment option [1][3][6] - The study reported no serious adverse events or discontinuations due to adverse events, highlighting the favorable safety profile of icovamenib [4][6] Study Design and Results - COVALENT-111 is a double-blinded, randomized, 3:1 placebo-controlled trial involving 225 adult patients with type 2 diabetes, assessing the efficacy and safety of icovamenib [2][3] - The study included three dosing arms, with the most effective being Arm B, which showed a mean HbA1c reduction of 0.5% [2][3] - Patients with severe insulin deficiency (SIDD) demonstrated the best response, achieving a mean HbA1c reduction of 1.47% in Arm B [3][4] Safety and Tolerability - Icovamenib was well-tolerated throughout the study, with no serious adverse events or drug-to-drug interactions reported [4][6] - The favorable safety profile supports the continued development of icovamenib as a treatment for type 2 diabetes [4][6] Future Plans - Biomea Fusion plans to present detailed results at a medical conference in 2025 and engage with the FDA to discuss the data [5][6] - The company aims to further explore icovamenib's potential as a first-in-class menin inhibitor therapy for type 2 diabetes [6][7] Mechanism of Action - Icovamenib is a potent, selective covalent inhibitor of menin, designed to regenerate insulin-producing beta cells, potentially offering a disease-modifying therapy for diabetes [10][11] - The mechanism of action involves enabling the proliferation and preservation of healthy, functional insulin-producing beta cells [10][11] Industry Context - Diabetes is a significant health issue, with over 37 million people in the U.S. affected, highlighting the need for innovative treatment options [12][13] - The economic burden of diabetes care is substantial, with a significant portion of healthcare costs allocated to managing the disease [13]

Core Insights - Biomea Fusion, Inc. is a clinical-stage biopharmaceutical company focused on developing oral covalent small molecules for treating diabetes, obesity, and genetically defined cancers [2][3] - The company will present topline results from its Phase II trial, COVALENT-111, for icovamenib in patients with type 2 diabetes on December 17, 2024 [1] Company Overview - Biomea Fusion specializes in the discovery and development of covalent small molecules, which form permanent bonds to target proteins, offering advantages such as greater target selectivity and lower drug exposure [2] - The company utilizes its proprietary FUSION™ System to design and develop next-generation covalent-binding small-molecule medicines aimed at maximizing clinical benefits for patients [3] Event Details - A conference call and webcast will be held on December 17, 2024, at 8:00 am EST to discuss the trial results, with a replay available on the company's website [1][2]

In preclinical experiments, icovamenib enhanced beta cell function and responsiveness of human islets to GLP-1-based therapies. These effects were associated with an increase in the expression levels of both the GLP-1 receptor (GLP-1R) as well as intracellular insulin.Overall results showed synergy of the combination therapy, which may allow lower doses of GLP-1-based therapies to achieve glycemic targets, potentially reducing side effects and improving tolerability of GLP-1 based therapies. REDWOOD CITY, C ...

Financial Performance - The company reported an accumulated deficit of $357.9 million as of September 30, 2024, with net losses of $109.1 million and $82.4 million for the nine months ended September 30, 2024, and 2023, respectively[61]. - The total operating expenses for the nine months ended September 30, 2024, were $114.0 million, an increase of $25.2 million compared to $88.8 million for the same period in 2023[68]. - Net cash used in operating activities for the nine months ended September 30, 2024, was $89.9 million, compared to $73.8 million for the same period in 2023[76][78]. - The net loss for the nine months ended September 30, 2024, was $109.1 million, offset by non-cash adjustments of $18.0 million[77]. - Interest and other income, net for the three months ended September 30, 2024, was $1.3 million, a decrease of $1.4 million compared to $2.7 million for the same period in 2023[68]. - The company has not generated any revenue from product sales and does not expect to do so until regulatory approval is obtained for a product candidate[61]. - The company has not generated any revenue to date and does not expect to do so in the near future[63]. Research and Development - Icovamenib demonstrated a placebo-adjusted mean percent change of A1c of -1.4% in the 200 mg cohort after 26 weeks, with 36% of participants achieving a durable glycemic response[49]. - The FDA lifted the clinical hold on the COVALENT-111 and COVALENT-112 trials in September 2024, allowing the company to continue its clinical investigations[52]. - The company expects to announce preclinical data for a third development candidate, BMF-650, in Q4 2024[43]. - The Phase 1/2 clinical trial COVALENT-111 for type 2 diabetes includes approximately 270 participants, with dosing durations up to 12 weeks[47]. - Icovamenib is being investigated in oncology through ongoing Phase 1 trials COVALENT-101 and COVALENT-102, focusing on liquid tumors and KRAS solid tumors, respectively[54]. - The company initiated dosing in the Phase 1 clinical trial COVALENT-101 in January 2022, targeting relapsed/refractory AML and ALL[55]. - BMF-500, a third-generation oral covalent small molecule inhibitor, was nominated in May 2022 and is currently in a Phase 1 study (COVALENT-103) for relapsed or refractory acute leukemia[61]. - The company anticipates completing dose escalation for COVALENT-101 and COVALENT-102 by the end of 2024[60]. - The company expects research and development expenses to increase substantially in the coming years as it seeks to initiate and complete clinical trials[63]. Expenses and Financial Outlook - Research and development expenses for the three months ended September 30, 2024, were $27.2 million, an increase of $1.9 million compared to $25.3 million for the same period in 2023[68]. - General and administrative expenses increased by $1.0 million during the three months ended September 30, 2024, primarily due to personnel-related costs[72]. - The company anticipates significant increases in general and administrative expenses due to staff expansion and compliance costs associated with being a public company[65]. - The company has substantial doubt about its ability to continue as a going concern without obtaining additional financing[73]. - The company anticipates needing to raise substantial additional capital to fund operations and product development, with requirements depending on various factors including clinical trials and regulatory reviews[74]. - The company sold 5,750,000 shares of common stock at a price of $30.00 per share in April 2023, resulting in net proceeds of $161.8 million[73]. - Net cash provided by financing activities was $1.3 million during the nine months ended September 30, 2024, significantly lower than $163.2 million in the same period of 2023[80][81]. Cash Position - As of September 30, 2024, the company had cash, cash equivalents, and restricted cash of $88.3 million and an accumulated deficit of $357.9 million[73]. - As of September 30, 2024, the company held $88.3 million in cash, cash equivalents, and restricted cash[85]. Market Risks - The company is exposed to market risks primarily related to interest rate sensitivities, with no significant foreign currency risk reported[85]. - The company has no material changes in contractual obligations from the previous reporting period[82]. - The company has not reported any off-balance sheet arrangements during the periods presented[82]. - Non-cash adjustments in operating activities included stock-based compensation expense of $14.6 million for the nine months ended September 30, 2024[77]. - The company may seek additional capital through various means, including public or private equity offerings and collaborations[74].

Exhibit 99.1 Biomea Fusion Reports Third Quarter 2024 Financial Results and Corporate Highlights • U.S. Food and Drug Administration (FDA) lifted Clinical Hold on COVALENT-111 (Type 2 Diabetes) & COVALENT112 (Type 1 Diabetes) trials • COVALENT-111 Phase 2b 26-week topline data of the dose expansion cohorts expected in December 2024 • COVALENT-112 Phase 2a 26-week topline data of the open label portion expected in December 2024 • On track to announce our third clinical candidate, BMF-650, for the treatment o ...

U.S. Food and Drug Administration (FDA) lifted Clinical Hold on COVALENT-111 (Type 2 Diabetes) & COVALENT-112 (Type 1 Diabetes) trialsCOVALENT-111 Phase 2b 26-week topline data of the dose expansion cohorts expected in December 2024COVALENT-112 Phase 2a 26-week topline data of the open label portion expected in December 2024On track to announce our third clinical candidate, BMF-650, for the treatment of diabetes and obesity – a next-generation, oral small-molecule GLP-1 receptor agonist (GLP-1 RA) - and pre ...