Summary of Biomea Fusion Conference Call - October 07, 2025 Company Overview - **Company**: Biomea Fusion (NasdaqGS: BMEA) - **Focus**: Development of acobaminib, a menin inhibitor for type 2 diabetes treatment Key Points from the Conference Call Clinical Study Results - **Study**: COVALENT-111, a phase 2 clinical trial assessing acobaminib's safety and efficacy in type 2 diabetes patients [5][6] - **Duration**: 52-week results presented, with a focus on the drug's effects on severe insulin-deficient patients and those on GLP-1 therapy [9][32] - **Efficacy**: - Severe insulin-deficient patients showed a mean HbA1c reduction of 1.5% compared to placebo, statistically significant with a p-value of 0.01 [16][32] - Patients on GLP-1 therapy who did not achieve target HbA1c levels experienced a 1.3% reduction [32] - **Durability**: HbA1c reductions were sustained for up to 52 weeks post-treatment, indicating potential long-term benefits [32][30] Mechanism of Action - **Menin Inhibition**: Acobaminib selectively inhibits menin, leading to increased beta cell mass and function, and enhanced GLP-1 receptor expression on beta cells [8][26] - **Clinical Implications**: This mechanism may provide a new treatment modality for patients with severe insulin deficiency, who currently have limited options [24][30] Safety Profile - **Safety Observations**: Acobaminib was generally well tolerated with no serious adverse events reported. The side effects included mild nausea and diarrhea [19][29] - **Long-term Monitoring**: Ongoing safety assessments are planned, especially regarding liver enzyme levels at higher doses [29][30] Future Directions - **Next Steps**: - Conducting a food effect study to optimize dosing and improve drug exposure [34] - Planning larger studies targeting severe insulin-deficient patients and those on GLP-1 therapy [33] - **Funding**: Recent public offering strengthens the company's financial position, extending cash runway into the second half of 2027 [34] Market Context - **Diabetes Treatment Landscape**: Current diabetes therapies often require chronic dosing and can have significant side effects. Acobaminib's episodic treatment approach may represent a significant advancement in diabetes care [30][64] - **Potential Impact**: If successful, acobaminib could become a cornerstone therapy for type 2 diabetes, particularly for difficult-to-treat patient populations [31][32] Additional Insights - **Patient Subtypes**: The study identified specific patient subtypes that respond best to acobaminib, including those with severe insulin deficiency and those inadequately controlled on GLP-1 therapies [9][33] - **Regulatory Pathway**: The company is optimistic about the FDA's acceptance of their novel treatment approach, which does not fit traditional chronic treatment guidelines [63][64] This summary encapsulates the critical findings and future directions discussed during the Biomea Fusion conference call, highlighting the potential of acobaminib in transforming diabetes treatment.

Group 1 - The article does not provide any specific content or key points related to a company or industry [1]

Efficacy of Icovamenib - In Severe Insulin-Deficient Diabetes (SIDD) patients (Arm B), 12 weeks of icovamenib treatment resulted in a mean HbA1c reduction of 1.5% at Week 52 (p=0.01)[46, 55, 65] - Patients on GLP-1 based therapy who were not achieving target HbA1c levels experienced a clinically meaningful HbA1c reduction of 1.3% at Week 52 (p=0.05) after 12 weeks of icovamenib treatment[56, 66] - Higher icovamenib exposure, measured by PK Mean AUC, was associated with greater HbA1c reduction across all dosing arms[43, 44] - The company believes data suggest that a readily achievable exposure level could provide ≥1.5% HbA1c reductions in T2D patients[47, 56] Safety and Tolerability - Icovamenib was generally well-tolerated, with no adverse-event related discontinuations and no related serious adverse events reported[29, 66, 70] - The percentage of patients with at least one Treatment Emergent Adverse Event (TEAE) in the combined icovamenib arms was 27% (55 out of 201 patients), comparable to the placebo arm at 27% (18 out of 66 patients)[59] - No deaths were reported in any of the treatment arms[59] Trial Design and Patient Characteristics - The COVALENT-111 study was a Phase 2 randomized, double-blind, placebo-controlled study in participants with Type 2 Diabetes (T2D)[10] - The study included 216 planned participants, with a 3:1 randomization ratio of icovamenib to placebo[11] - The Per Protocol Population on 1 or More Antihyperglycemic Agents at Baseline included 163 patients, with 114 in the combined icovamenib arms and 49 in the placebo arm[15, 17, 18] Next Steps - The company plans to optimize icovamenib exposure and define dosing criteria with a Food Effect Study (COVALENT-121)[71] - The company plans to investigate icovamenib in severe insulin deficient diabetes patients in a Phase IIb Type 2 Diabetes Study (COVALENT-211)[71] - The company plans to investigate icovamenib in combination with a GLP-1 based therapy in a Phase II Type 2 Diabetes Study (COVALENT-212)[71]

Biomea Fusion (NASDAQ:BMEA) shares rose after reporting positive results from its mid-stage study testing icovamenib in individuals with type 2 diabetes over a 52-week period. The stock closed up 24% on Monday. The study found that icovamenib provided lasting treatment ...

Core Insights - Biomea Fusion, Inc. announced positive 52-week results from its Phase II COVALENT-111 study for icovamenib in type 2 diabetes patients, indicating durable efficacy and safety [1][2][5] Study Design and Results - COVALENT-111 is a double-blind, randomized, placebo-controlled trial involving adult patients with type 2 diabetes diagnosed within the last 7 years, with specific HbA1c and BMI criteria [3][4] - The study evaluated three dosing regimens of icovamenib, with a total of 267 patients receiving at least one dose, focusing on a modified intent-to-treat population of 163 patients [4] - Positive results were observed across multiple subgroups, with severe insulin-deficient patients showing a durable HbA1c reduction of 1.2% (p=0.01) sustained through Week 52 [5][8] - Patients on GLP-1-based therapy who did not achieve glycemic targets also showed a 1.3% reduction in HbA1c (p=0.05) after 8 or 12 weeks of treatment [6][8] Safety Profile - Icovamenib maintained a favorable safety profile throughout the 52-week observation period, with no treatment-related serious adverse events reported [7][8] Future Plans - The company plans to initiate Phase II trials in severe insulin-deficient diabetes patients and those not achieving glycemic targets with GLP-1 therapy in the fourth quarter of 2025 [8][15] Mechanism of Action - Icovamenib is a selective covalent inhibitor of menin, which is believed to enable the proliferation and preservation of healthy insulin-producing beta cells, addressing the underlying dysfunction in diabetes [12][13] Market Context - Diabetes is a significant health issue, with over 38 million people in the U.S. affected, highlighting the need for effective treatments [14]

Core Points - Biomea Fusion, Inc. granted non-qualified stock options to a new employee for 48,000 shares, vesting quarterly over four years [1][2] - The stock option award is part of Biomea's 2023 Inducement Equity Plan, adopted on November 17, 2023 [2] - Biomea Fusion focuses on developing oral small molecules for diabetes and obesity treatment, aiming to improve patient lives [3]

Core Insights - Biomea Fusion, Inc. presented preclinical data on its investigational menin inhibitor icovamenib in combination with semaglutide, showing enhanced body weight loss and glycemic control in a Type 2 Diabetes (T2D) animal model [1][2][3] Preclinical Findings - In a Zucker diabetic fatty (ZDF) rat model, the combination therapy of icovamenib and low-dose semaglutide resulted in significant improvements compared to semaglutide alone, including a 60% mean reduction in fasting blood glucose after two weeks and a 50% lower mean glucose AUC during an oral glucose tolerance test [5][7] - The combination therapy led to a greater mean body weight loss of -12.5% compared to -3.4% for semaglutide alone, with the weight loss driven entirely by fat mass reduction while preserving lean mass [7] Clinical Development Plans - Biomea plans to advance clinical evaluation of icovamenib in combination with GLP-1 therapies, with a Phase II study expected to begin in the second half of 2025 [5][8] - The company has received FDA clearance for the Investigational New Drug Application (IND) for its next-generation oral GLP-1 receptor agonist, BMF-650, with a Phase I clinical trial in obesity set to initiate soon [6][8] Mechanism of Action - Icovamenib is designed to inhibit menin, which is believed to support beta cell regeneration, potentially reversing the progression of T2D by enhancing insulin-producing beta cell function [9][11] Market Context - Diabetes is a significant health issue in the U.S., with over 37 million people affected and a substantial economic burden on the healthcare system, indicating a strong need for effective treatments [10]

Core Insights - Biomea Fusion reported a net loss of $20.7 million for Q2 2025, a significant reduction from $37.3 million in Q2 2024, and beat consensus estimates with a loss of $0.51 per share compared to an expected loss of $0.53 per share [1][2] - The company recorded no revenue, aligning with expectations for a pre-commercial-stage firm, while demonstrating progress in financial efficiency through major cost reductions in research and administrative expenses [1][5] Financial Performance - Net loss decreased by 44.5% year-over-year from $37.3 million in Q2 2024 to $20.7 million in Q2 2025 [2][5] - Research and development expenses were reduced to $16.6 million from $31.8 million in the same period last year, a decrease of 47.8% [2][5] - General and administrative expenses also fell to $4.7 million from $7.1 million, a decrease of 33.8% [2][5] - Total cash as of June 30, 2025, was $56.6 million, with an additional $42.8 million raised through an equity offering during the quarter [5][11] Business Model and Strategic Focus - Biomea Fusion is focused on developing covalent small molecules for metabolic diseases, particularly type 2 diabetes and obesity, with icovamenib as its lead candidate [3][4] - The company aims to address the root causes of diabetes rather than just glucose levels, positioning icovamenib as a potential disease-modifying agent [3] Clinical Developments - The COVALENT-111 Phase II study of icovamenib showed promising results, including reduced hemoglobin A1c levels and improved beta cell function [6][8] - Preclinical studies indicated that icovamenib combined with semaglutide resulted in greater reductions in blood sugar and body weight compared to semaglutide alone [6][7] - Upcoming clinical catalysts include 52-week data from the COVALENT-111 study and additional Phase II studies in difficult-to-treat diabetes populations [8][12] Future Outlook - The company did not provide specific financial guidance but indicated that available cash is expected to fund operations into the second half of 2026 [11] - Future operating expenses are projected to be about 40% lower than in Q2 2025, reflecting planned cost reductions [11][12] - Key developments to monitor include long-term data from ongoing trials and regulatory steps for BMF-650 in obesity [12]

Financial Performance - As of June 30, 2025, the company had an accumulated deficit of $437.3 million and incurred net losses of $50.0 million for the six months ended June 30, 2025, compared to $76.3 million for the same period in 2024, reflecting a decrease of $26.3 million [77]. - Total operating expenses for the six months ended June 30, 2025, were $50.988 million, down from $79.957 million in 2024, a reduction of $28.969 million [93]. - The company expects to continue incurring significant losses for the foreseeable future, with expenses anticipated to increase as clinical trials and research activities progress [78]. - Net cash used in operating activities was $44.9 million for the six months ended June 30, 2025, compared to $64.7 million for the same period in 2024 [111]. - The company has incurred substantial operating losses and will require additional financing to continue operations beyond the second half of 2026 [104]. Research and Development - Research and development expenses for the six months ended June 30, 2025, were $39.463 million, a decrease of $26.138 million from $65.601 million in 2024 [93]. - Research and development expenses decreased by $15.3 million to $16.6 million for the three months ended June 30, 2025, compared to $31.8 million for the same period in 2024 [94]. - Total research and development expenses decreased by $26.1 million to $39.5 million for the six months ended June 30, 2025, compared to $65.6 million for the same period in 2024 [96]. - The company is currently evaluating icovamenib in two ongoing Phase II clinical trials for type 1 and type 2 diabetes, with a strategic focus on diabetes and obesity medicines [74]. - The company plans to advance BMF-650, a next-generation oral small molecule GLP-1 receptor agonist, through IND-enabling studies, aiming to provide a best-in-class therapeutic option for diabetes and obesity [75]. Capital and Financing - In June 2025, the company issued 19,450,000 shares of common stock at an offering price of $2.00 per share, generating approximately $42.8 million in gross proceeds [82]. - The company will need to raise additional capital in the future to fund operations and complete clinical trials for product candidates [79]. - The company anticipates needing to raise substantial additional capital to fund operations and develop product candidates [106]. - The company completed a public offering in June 2025, issuing 19,450,000 shares at $2.00 per share, resulting in net proceeds of approximately $37.2 million [102]. - The company has $94.8 million available under the 2022 ATM Program as of June 30, 2025 [103]. Cash and Liquidity - As of June 30, 2025, the company had cash, cash equivalents, and restricted cash of $56.6 million and an accumulated deficit of $437.3 million [104]. - The company held $56.6 million in cash, cash equivalents, and restricted cash as of June 30, 2025 [120]. - Cash equivalents consisted of money market funds, while restricted cash included two stand-by letters of credit related to lab leases [120]. - Net cash provided by financing activities was $42.8 million during the six months ended June 30, 2025, primarily from issuances of common stock and pre-funded warrants [114]. Risk Management - The company is exposed to market risks primarily related to interest rate sensitivities [120]. - There was no material foreign currency risk for the quarter ended June 30, 2025 [120]. - Historical fluctuations in interest rates have not been significant for the company [120]. - An immediate 10% relative change in interest rates would not have a material effect on the fair market value of cash equivalents due to their short-term maturities [120]. - The primary objectives of the company's investment activities are to ensure liquidity and preserve capital [120]. Accounting Policies - There were no material changes to critical accounting policies from those discussed in the Annual Report on Form 10-K filed on March 31, 2025 [119]. - The company had no interest-bearing liabilities as of June 30, 2025 [120]. - The company’s estimates and assumptions affect the reported amounts of assets and liabilities, which are based on historical experience and other reasonable factors [118].

Company Overview and Q2 2025 Highlights Biomea Fusion, a clinical-stage diabetes and obesity company, reported Q2 2025 results, highlighting clinical data and a **$42.8 million** financing [Introduction and CEO Commentary](index=1&type=section&id=1.1.%20Introduction%20and%20CEO%20Commentary) The Interim CEO highlighted positive clinical and preclinical data for icovamenib and BMF-650, and a **$42.8 million** equity financing to advance programs - Biomea Fusion is a clinical-stage diabetes and obesity company[2](index=2&type=chunk) - Icovamenib demonstrated potential as a novel, potentially first-in-class investigational agent for type 2 diabetes and obesity, with preclinical data showing superior glycemic control and weight reduction in combination with low-dose semaglutide, while fully preserving lean mass[3](index=3&type=chunk) - BMF-650 showed encouraging results in obese cynomolgus monkeys, achieving up to **15% weight reduction** and robust dose-dependent appetite suppression, reinforcing its potential as an oral GLP-1 RA[3](index=3&type=chunk) - Completed a **$42.8 million** equity financing to advance high-priority diabetes and obesity programs[3](index=3&type=chunk) [Second Quarter 2025 Corporate Highlights](index=1&type=section&id=1.2.%20Second%20Quarter%202025%20Corporate%20Highlights) Q2 2025 highlights included icovamenib presentations, robust BMF-650 preclinical results, a **$42.8 million** public offering, and workforce reduction to optimize expenses - Three presentations at ADA 2025 highlighted icovamenib's therapeutic potential, demonstrating durable HbA1c reduction and improved beta-cell function in T2D patients, and promoting healthy myotube morphology[5](index=5&type=chunk)[6](index=6&type=chunk) - BMF-650 demonstrated robust, dose-dependent weight loss and appetite suppression in obese non-human primates; planned Investigational New Drug (IND) submission remains on track for the second half of 2025[5](index=5&type=chunk) - Raised approximately **$42.8 million** in gross proceeds through a public offering, extending projected cash runway into the second half of 2026[5](index=5&type=chunk) - Reduced workforce and quarterly expenses to support core programs, anticipating future quarterly operational expenses to be approximately **40% lower**[5](index=5&type=chunk)[8](index=8&type=chunk) Clinical Development Program Updates Updates on clinical development programs for icovamenib, BMF-650, and BMF-500 detail their progress and key findings [Icovamenib (Oral Small Molecule Menin Inhibitor for T2D and T1D)](index=1&type=section&id=2.1.%20Icovamenib%20%28Oral%20Small%20Molecule%20Menin%20Inhibitor%20for%20T2D%20and%20T1D%29) Icovamenib showed significant therapeutic potential in T2D patients with durable HbA1c reduction and enhanced beta-cell function, and superior metabolic benefits in preclinical models - In T2D patients, icovamenib demonstrated durable HbA1c reduction and enhanced beta-cell function three months post-dosing, particularly in severe insulin deficient patients enrolled in its Phase II trial[6](index=6&type=chunk) - In a ZDF rat model of T2D, treatment of icovamenib in combination with low-dose semaglutide delivered superior metabolic benefits compared to low-dose semaglutide alone, including[10](index=10&type=chunk) Fasting Blood Glucose, Glucose OGTT AUC, HbA1c Decline, HOMA-IR (Insulin Resistance), C-peptide to Glucose Ratio, Body Weight Reduction | Metric | Icovamenib + Low-dose Semaglutide vs. Low-dose Semaglutide Alone | | :-------------------------------- | :---------------------------------------------------------------- | | Fasting Blood Glucose | **60% lower** | | Glucose OGTT AUC | **50% lower** | | HbA1c Decline | **>1% by Day 28** and **>2% by Day 39** | | HOMA-IR (Insulin Resistance) | **75% lower** | | C-peptide to Glucose Ratio | **2-fold increase** | | Body Weight Reduction | **10% greater**, primarily due to fat mass reduction with complete lean mass preservation | - Icovamenib also promoted healthy myotube morphology and diminished drug-induced atrophy in ex vivo human myotube cultures[10](index=10&type=chunk) [BMF-650 (Next-generation Oral Small Molecule GLP-1 RA for Obesity)](index=2&type=section&id=2.2.%20BMF-650%20%28Next-generation%20Oral%20Small%20Molecule%20GLP-1%20RA%20for%20Obesity%29) BMF-650 demonstrated rapid, dose-dependent reductions in food intake and significant weight loss in obese cynomolgus monkeys, achieving average weight reductions of **15%** at the higher dose - In a 28-day study in obese cynomolgus monkeys, BMF-650 achieved rapid, dose-dependent reductions in food intake and significant weight loss, with average weight reductions of **15%** at the higher dose of 30 mg/kg/day[10](index=10&type=chunk) - BMF-650 was generally well tolerated across all dose levels and showed no aminotransferase elevations[10](index=10&type=chunk) - These preclinical results compare favorably to published preclinical data from other leading oral GLP-1 RA candidates in development, supporting BMF-650's potential as a best-in-class oral small-molecule GLP-1 RA[10](index=10&type=chunk) [BMF-500 (Oral Small Molecule FLT3 Inhibitor in Acute Myeloid Leukemia ("AML"))](index=2&type=section&id=2.3.%20BMF-500%20%28Oral%20Small%20Molecule%20FLT3%20Inhibitor%20in%20Acute%20Myeloid%20Leukemia%20%28%22AML%22%29%29) Updated Phase I data for BMF-500 in relapsed/refractory FLT3-mutant AML patients showed sustained antileukemic responses, deep bone marrow blast reductions, and survival benefit; the company is now exploring strategic partnerships - Presented updated Phase I data at EHA 2025, showing sustained antileukemic responses, deep bone marrow blast reductions, and survival benefit in relapsed/refractory FLT3-mutant AML patients, all of whom had failed FLT3 inhibitor gilteritinib[10](index=10&type=chunk) - The Company concluded its oncology efforts and is now exploring strategic partnerships for BMF-500[10](index=10&type=chunk) Key Anticipated 2025 Milestones Biomea Fusion anticipates key milestones for icovamenib and BMF-650 in 2025, including clinical data releases and IND submission [Icovamenib Milestones](index=2&type=section&id=3.1.%20Icovamenib%20Milestones) Biomea Fusion anticipates 52-week data from the Phase II COVALENT-111 study, initiation of a new Phase II study for T2D, and preliminary data from the Phase II COVALENT-112 study in T1D in the second half of 2025 - 52-week data from the Phase II COVALENT-111 study in T2D expected in the second half of 2025[12](index=12&type=chunk) - Initiation of Phase II study of icovamenib in T2D patients currently uncontrolled on a GLP-1 based therapy in the second half of 2025[12](index=12&type=chunk) - Preliminary data from the Phase II COVALENT-112 study in T1D anticipated in the second half of 2025[12](index=12&type=chunk) [BMF-650 Milestones](index=3&type=section&id=3.2.%20BMF-650%20Milestones) Key milestones for BMF-650 in 2025 include the planned submission of the Investigational New Drug (IND) application and the anticipated initiation of a Phase I study in obese, otherwise healthy volunteers - Submission of the IND application for BMF-650 is planned for the second half of 2025[12](index=12&type=chunk) - Phase I study initiation in obese, otherwise healthy volunteers anticipated by late 2025, pending regulatory clearance[12](index=12&type=chunk) Second Quarter 2025 Financial Results Biomea Fusion reported a reduced net loss for Q2 and H1 2025, driven by decreased R&D and G&A expenses, with **$56.6 million** cash expected to fund operations into H2 2026 [Financial Summary](index=3&type=section&id=4.1.%20Financial%20Summary) Biomea Fusion reported a reduced net loss for Q2 and H1 2025, primarily due to significant decreases in R&D and G&A expenses, with **$56.6 million** in cash expected to fund operations into H2 2026 Cash, Cash Equivalents, and Restricted Cash | As of | Amount (in millions) | | :---- | :------------------- | | June 30, 2025 | **$56.6** | | Expected Runway | Into H2 2026 | Net Loss Attributable to Common Stockholders (in millions) | Period | 2025 | 2024 | Change (YoY) | | :----- | :--- | :--- | :----------- | | Q2 Ended June 30 | **$(20.7)** | $(37.3) | **$(16.6) decrease** | | H1 Ended June 30 | **$(50.0)** | $(76.3) | **$(26.3) decrease** | Research and Development (R&D) Expenses (in millions) | Period | 2025 | 2024 | Decrease (YoY) | Primary Drivers | | :----- | :--- | :--- | :------------- | :-------------- | | Q2 Ended June 30 | **$16.6** | $31.8 | **$15.3** | Clinical activities (**$9.1M**), preclinical/explor