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1COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 COVALENT-111 Phase II Study Icovamenib in Type 2 Diabetes 52-Week Results October 7, 2025
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2COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Legal Disclaimer & Forward-Looking Statements Certain statements in this presentation and the accompanying oral commentary are forward-looking statements. These statements relate to future events or the future business and financial performance of Biomea Fusion, Inc. (the “Company”) and involve known and unknown risks, uncertainties and other factors that may cause the actual results, levels of activity, performance or achievements of the Company or its industry to be materially different from those expressed or implied by any forward-looking statements. In some cases, forward-looking statements can be identified by terminology such as “may, ” “will, ” “could, ” “would, ” “should, ” “expect, ” “plan, ” “anticipate, ” “intend, ” “believe, ” “estimate, ” “predict, ” “potential” or other comparable terminology. All statements other than statements of historical fact could be deemed forward-looking, including any projections of financial information or profitability, the initiation, timing and results of pending or future preclinical studies and clinical trials, the actual or potential actions of the FDA, the status and timing of ongoing research, any statements about historical results that may suggest trends for the Company's business; any statements of the plans, strategies, and objectives of management for future operations; and other factors affecting the Company's financial condition or operations. The Company has based these forward-looking statements on its current expectations, assumptions, estimates and projections. While the Company believes these expectations, assumptions, estimates and projections are reasonable, such forward-looking statements are only predictions and involve known and unknown risks and uncertainties, many of which are beyond the Company's control. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our most recent annual report on Form 10-K and quarterly reports on Form 10-Q filed with the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors in our other subsequent filings with the Securities and Exchange Commission. The forward- looking statements in this presentation are made only as of the date hereof. Except as required by law, the Company assumes no obligation and does not intend to update these forward-looking statements or to conform these statements to actual results or to changes in the Company's expectations. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk.
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3COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Agenda COVALENT-111 – A Phase II Study of Icovamenib in Type 2 Diabetes 52-Week Follow Up - Conference Call October 3, 2025 Ramses Erdtmann Founder and Chief Operating Officer & President,Biomea Fusion COVALENT-111 52-Week Follow-up Results Key Opinion Leader Insights Introduction Question & Answer Session Juan Pablo Frias, MD Co-Chair of the Scientific Advisory Board, Biomea Fusion Ralph DeFronzo, MD Professor of Medicine, Chief of Diabetes Division at the University of Texas Health Science Center at San Antonio and Deputy Director of the Texas Diabetes Institute Mick Hitchcock, PhD Interim Chief Executive Officer & Board Member,Biomea Fusion Executive Summary
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4COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 COVALENT-111, A Phase II Study of Icovamenib in Type 2 Diabetes 52-Week Follow Up Data Dr. Juan Pablo Frias Chief Medical Officer of Biomea Fusion Juan Pablo Frias, MD Co-Chair of the Scientific Advisory Board, Biomea Fusion
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5COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Increased Beta Cell Mass and Function Increased GLP-1 Receptor Expression & Incretin Effect Beta Cell Quantity & Function GLP-1 Receptor Expression Dual Effect Enhanced Weight Loss with Preservation of Muscle Mass in Preclinical Combination Studies Increased Insulin Synthesis and Secretion Icovamenib: Potential Disease-Modifying Candidate for Diabetes Mechanism of Action: Selective & Partial Menin Inhibition Icovamenib Differentiating Features Oral - Convenient, once- daily oral therapy Non-Chronic – Limited duration dosing with sustained effect Generally Well Tolerated – Favorable safety profile observed to date MOA complementary to other antihyperglycemic agents used
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6COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Trial Design Phase 2 Randomized, Double-Blind, Placebo-controlled Study in Participants – ALL SUBTYPES - with T2D 3:1 N=216 Planned Participants Eligibility Criteria • Adults (18-65 years) with T2D (<7 years) • HbA1c 7.0-10.5% • BMI 25-40 kg/m2 • Treated with up to 3 antidiabetic agents (excluding insulin and SFUs) • N=72 participants per arm (3:1 ratio, icovamenib: PBO) icovamenib x12 wks 100 mg (QD) Change of HbA1c achieving an HbA1c BID: twice daily BMI: Body Mass Index HbA1c: glycated hemoglobin PBO: Placebo QD: daily SFUs: sulfonylureas T2D: Type 2 Diabetes icovamenib x8 wks 100 mg (QD) icovamenib x8 wks 100 mg (QD) placebo x4 wks 100 mg (QD) icovamenib x4 wks 100 mg (BID) Primary Endpoints • Change in HbA1c from baseline at Week 26 • Safety and tolerability at Week 52 Secondary / Exploratory Endpoints • Change in HbA1c from baseline at Week 52 • Measure of beta-cell function (plasma glucose, c-peptide, insulin, HOMA-β and HOMA-IR) at Week 26
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7COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 COVALENT-111 Statistical Analysis Plan Read Out of Insulin-Deficient and Insulin Resistant Subgroups at Weeks 26 and 52 Statistical Analysis Plan for COVALENT-111 Prespecified subgroup analysis to include assessment of HbA1c change within each T2D subgroup (SIDD, MARD, MOD, and SIRD) Subgroup analysis based on algorithm established per Ahlqvist et al. (Lancet Diabetes Endocrinol. 2018;6:361-369) Arm A, B, and C primary analysis: change in HbA1c
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8COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Baseline Demographics and Characteristics Per Protocol Population* on 1 or More Antihyperglycemic Agents at Baseline (N=163) Parameter Mean (SD) or % Arm A icovamenib (8 wks 100mg QD) (N=45) Arm B icovamenib (12 wks 100 mg QD) (N=36) Arm C icovamenib (8 wks 100 mg QD then 4 wks of 100mg BID) (N=33) Combined Arms icovamenib (N=114) Combined Arms placebo (N=49) Age (yr) 55 (7) 56 (6) 51 (10) 54 (8) 55 (7) Duration of T2D Diagnosis (yr) 4.3 (1.8) 4.7 (1.8) 4.2 (2.2) 4.4 (1.9) 4.3 (2.0) Sex (% Female) (31) (56) (36) (40) (43) HbA1c % (SD) 8.3 (1.1) 8.3 (1.0) 8.0 (0.8) 8.2 (1.0) 8.3 (1.0) Fasting C-peptide (ng/mL) 3.4 (1.2) 3.8 (1.5) 3.7 (1.8) 3.6 (1.5) 3.5 (1.4) BMI (kg/m2) 30.9 (4.7) 32.7 (4.5) 32.4 (4.9) 31.9 (4.7) 32.6 (4.2) BMI <30 kg/m2 (%) (49) (22) (30) (35) (27) BMI ≥30 kg/m2 (%) (51) (75) (70) (64) (73) Demographics and baseline characteristics were well matched between icovamenib- and placebo-treated participants *Per the Covalent 111 Protocol the population analyzed includes only subjects who received ≥80% of their planned dosing. A clinical hold interrupted the dosing. Patients were also excluded if they had significant protocol deviation
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9COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Antihyperglycemic Agents at Baseline Per Protocol Population* on 1 or More Antihyperglycemic Agents at Baseline (N=163) Parameter Arm A icovamenib (8 wks 100mg QD) (N=45) Arm B icovamenib (12 wks 100 mg QD) (N=36) Arm C icovamenib (8 wks 100 mg QD then 4 wks of 100mg BID) (N=33) Combined Arms icovamenib (N=114) Combined Arms placebo (N=49) Number of T2D Medications, n (%) 1 39 (87) 23 (64) 23 (70) 85 (75) 41 (84) 2 4 (9) 11 (31) 7 (21) 22 (19) 6 (12) 3 2 (4) 2 (6) 3 (9) 7 (6) 2 (4) Metformin Monotherapy, n (%) 36 (80) 18 (50) 22 (67) 76 (67) 38 (78) SGLT2i, n (%) 6 (13) 12 (33) 8 (24) 26 (23) 7 (14) DPP4i, n (%) 3 (7) 4 (11) 3 (9) 10(9) 2 (4) GLP-1 based medicines, n (%) 3 (7) 3 (8) 5 (15) 11 (10) 4 (8) Most participants treated with metformin monotherapy, with approximately 20% treated with SGLT2i, 10% with DPP4i, and 10% with GLP-1 based medicines
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10COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 T2D Subtype at Baseline Per Protocol Population* on 1 or More Antihyperglycemic Agents at Baseline (N=163) Parameter Arm A icovamenib (8 wks 100mg QD) (N=45) Arm B icovamenib (12 wks 100 mg QD) (N=36) Arm C icovamenib (8 wks 100 mg QD then 4 wks of 100mg BID) (N=33) Combined Arms icovamenib (N=114) Combined Arms placebo (N=49) SIDD, n (%) 11 (24) 6 (17) 4 (12) 21 (18) 12 (24) MARD, n (%) 11 (24) 6 (17) 5 (15) 22 (19) 8 (16) MOD, n (%) 21 (47) 22 (61) 22 (67) 65 (57) 24 (49) SIRD, n (%) 2 (4) 2 (6) 2 (6) 6 (5) 5 (10) SIDD = Severe Insulin-Deficient Diabetes MARD = Mild Age-Related Diabetes MOD = Mild Obesity-Related Diabetes SIRD = Severe Insulin-Resistant Diabetes
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11COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Mild obesity- related diabetes (MOD) Type 2 Diabetes is a Heterogeneous Disease – Two Core Drivers INSULIN-DEFICIENT DIABETES INSULIN RESISTANT DIABETES Ahlqvist et al. Lancet Diabetes Endocrinol 2018; 6: 361–69 18% Severe insulin- deficient diabetes (SIDD) Mild age-related diabetes (MARD) 39% 22% 15% Severe insulin resistant diabetes (SIRD) Median HOMA-B 49% Median HbA1c 8.3% Median BMI 29 kg/m2 Median HOMA-B 64% Median HbA1c 7.0% Median BMI 29 kg/m2 Median HOMA-B 74% Median HbA1c 7.2% Median BMI 36 kg/m2 Median HOMA-B 101% Median HbA1c 7.0% Median BMI 34 kg/m2 Initial target group for icovamenib Analysis from two independent 4,000 patient studies, (ADOPT and RECORD)
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12COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Icovamenib in Type 2 Diabetes - Learnings through Week 26 • Icovamenib is being assessed as a short-duration treatment (12 weeks) while all approved type 2 diabetes agents are chronic therapies • Primary endpoint is 26-Week HbA1c reduction (3 months post dosing) and tolerability at Week 52 with the secondary endpoint being 52-Week HbA1c reduction (9 months post dosing) • 26-Week Data: ▪ Prespecified subgroup of severe insulin-deficient diabetes patients performed the best ▪ Patients not achieving target HbA1c with a GLP-1-based therapy at study entry also achieved a clinically meaningful reduction in HbA1c Question after 26-week analysis? Will these results be maintained at Week 52 in Severe Insulin-Deficient Diabetes patients and those who are failing on a GLP-1-based therapy?
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13COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 High Unmet Need in Diabetes • Highest treatment failure rates among all T2D subtypes6 • Lowest insulin production of all adults with T2D6 • Represents a very high unmet medical need, with the highest risk of retinopathy, neuropathy 6 • Severe Insulin-Deficient Diabetes patients progress the fastest to insulin therapies6 18-44% Worldwide depending on ethnicity 2-4 ~165M Severe Insulin-Deficient T2D worldwide cases5 Nathan, et al. N Engl J Med 2022;387:1063-107 Severe Insulin-Deficient Diabetes Mean time to Loss of Glucose Control (A1c>7%) • Diabetes is a progressive disease • Approved agents are all chronic, none address the root cause – the failing beta cell • Average time to loss of glucose control with a SOC T2D therapy ranges from 2 - 2.5 years • 47.1% of T2D are uncontrolled with HbA1c > 7%1 1. Centers for Disease Control and Prevention (CDC). 2. Ahlqvist et al Diabetes 2020;69:2086–2093. 3. Mohan V. Diabetes Care 2025;48:153–163. 4. Song A. et al. Front Endocrinol. 2022;13:978612. 5. International Diabetes Federation. IDF Diabetes Atlas www.diabetesatlas.org (Based on company calculations): 6. Ahlqvist et al. Lancet Diabetes Endocrinol 2018;
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14COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Icovamenib in Type 2 Diabetes: 52-Week Highlights in Patients on 1 or more Antihyperglycemic Agent - 9 Months After Last Dose Icovamenib achieved clinically meaningful HbA1c reduction in multiple subgroups Sustained treatment effect in pre-defined severe insulin-deficient patient population Continued benefit observed in severe insulin-deficient diabetes patients Treatment effect in GLP-1 failures also improved and continued Demonstrated marked levels of activity in patients not achieving HbA1c target on GLP-1 therapy at study entry Higher icovamenib exposure led to improved responses PK analysis shows that better HbA1c reductions occurred in patients with better exposure to the drug Favorable safety profile continued Icovamenib was generally well-tolerated, with no adverse-event related discontinuations and no related serious adverse events
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15COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 All Dosing Arms A, B and C 52-Week Data
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16COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Change in HbA1c from Baseline through Week 52 – All Subtypes Across Treatment Durations (Arm A = 8 weeks 100 mg, Arm B = 12 weeks 100 mg, Arm C = 8 weeks 100 mg 4 weeks at 200 mg) Per Protocol participants taking one or more antihyperglycemic medications at baseline 0.5% threshold for clinical significance CMS Clinical Endpoints Review (2024) All presented data utilized a while-on-treatment estimand with mixed model repeated measures (MMRM) analysis and was censored for use of rescue medication, defined as any modification in anti-diabetic therapy
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17COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 12 Weeks of Dosing (Arms B & C) Delivered Lasting Benefit Through 52 Weeks for Severe Insulin-Deficient Diabetes Patients (9 Months After Last Dose) Severe Insulin-Deficient Diabetes Patients Arms B & C w/12 Weeks of Treatment (n=10 Active; n=12 Placebo) Arm B: 12 weeks of dosing 100 mg QD; Arm C: 8 weeks of 100 mg QD + 4 weeks of 100 BID -0.5% threshold for clinical significance CMS Clinical Endpoints Review (2024) Arm A was excluded from this analysis because it included only 8 weeks of dosing which the company is not planning to pursue.
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18COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 12 Weeks of Dosing (Arm B) Delivered Most Improved Results Through 52 Weeks for Severe Insulin-Deficient Diabetes Patients (9 Months Post Dosing) Severe Insulin-Deficient Diabetes Patients only Arm B w/12 Weeks of Treatment at 100 mg QD (n=6 Active; n=12 Placebo) Arm B: 12 weeks of dosing 100 mg QD -0.5% threshold for clinical significance CMS Clinical Endpoints Review (2024)
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19COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Why did Arm B perform better than Arm C in Severe Insulin-Deficient Patients? Patients in Arm B had greater icovamenib exposure which may have led to greater HbA1c reduction than Arms A and C Arm A: 8 weeks of dosing 100mg QD; Arm B: 12 weeks of dosing 100 mg QD; Arm C: 8 weeks of 100 mg QD + 4 weeks of 100 BID N=11 N=6 N=4 PK Mean AUC (Pharmacokinetic Mean Area Under the Curve) is a summary metric to evaluate drug exposure during dosing using PK concentration data collected at multiple time points across different visits. PK values of 0 (zero) are also included.
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20COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Higher HbA1c Reduction was Associated with Higher Icovamenib Exposure Week 52, All Dosing Arms (N=114), HbA1c Reduction vs. Icovamenib Exposure (Mean AUC) Reduction in HbA1c 273 218 207 184 0 50 100 150 200 250 300 ≥2.0% ≥1.5% ≥1.0% ≥0.5% PK (Mean AUC) Food type and timing of dosing impact icovamenib's pharmacokinetics. Food-effect study under way to optimize dosing instructions, which we expect will further improve exposure and improve consistency of outcome across patients.
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21COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 KEY FINDINGS through 52 Weeks Per Protocol participants taking one or more antihyperglycemic medications at baseline • Continued HbA1c reduction achieved at Week 52 in predefined subset of patients Severe insulin-deficient T2D patients (Arm B) showed the greatest clinically meaningful response (mean HbA1c reduction of 1.5%, p=0.01) through Week 52. • Exposure-response correlation Patients with the greatest exposure achieved the highest reduction in HbA1c. We believe data suggest that a readily achievable exposure level could provide ≥1.5% HbA1c reductions in T2D patients.
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22COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Efficacy of Icovamenib in Patients on GLP-1-Based Therapy 52-Week Data
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23COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Patients on a GLP-1 Based Therapy at Enrollment (n=11, All Obese Patients) Showed Durable and Clinically Meaningful Response 9 Months After Last Dose Post-hoc Analysis of Enrolled Patients on GLP-1 Therapy Not Achieving Target HbA1c <7.0% (n=11 Active; n=4 Placebo) -0.5% threshold for clinical significance CMS Clinical Endpoints Review (2024)
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24COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Icovamenib Prespecified Subgroup Performed with its Early Results in-line with Top-performing Chronically-Dosed Diabetes Agents Currently Approved Type 2 Diabetes Agents w/Chronic Dosing Therapy Dosing Regimen Administration Route Observation Period Mean HbA1c Reduction (placebo adj. %) Ozempic (GLP 1 Agonist) Chronic Dosing Injectable Week 30 -1.2 (0.5mg) -1.4 (1mg) Mounjaro (GLP-1/GIP Agonist) Chronic Dosing Injectable Week 40 -1.8 (5mg) -1.7 (15mg) Jardiance (SGLT2 Inhibitor) Chronic Dosing Oral Week 24 -0.7 (10mg) -0.9 (25mg) Januvia (DPP4 Inhibitor) Chronic Dosing Oral Week 24 -0.8 (100mg) ICOVAMENIB (Menin Inhibitor) 12 Weeks Oral Week 52 -1.5% to -1.8% (100mg) Ozempic FDA Label; Mounjaro FDA Label; Jardiance FDA Label; Januvia FDA Label Disclaimer: The data presented above are based on cross-study comparisons and are not based on any head-to-head clinical trials. Cross-study comparisons are inherently limited and may suggest misleading similarities and differences. The values shown in the cross-study comparisons are directional and may not be directly comparable.
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25COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 KEY FINDINGS through 52 Weeks Per Protocol participants taking one or more antihyperglycemic medications at baseline • Continued HbA1c reduction achieved at Week 52 in predefined subset of patients Severe insulin-deficient T2D patients (Arm B) showed the greatest clinically meaningful response (mean HbA1c reduction of 1.5%, p=0.01) through Week 52. • Exposure-response correlation Patients with the greatest exposure achieved the highest reduction in HbA1c. We believe data suggest that a readily achievable exposure level could provide ≥1.5% HbA1c reductions in T2D patients. • GLP-1 failing patients benefited markedly from 12 weeks of icovamenib Patients not achieving HbA1c targets with GLP-1 based therapy showed clinically meaningful responses (HbA1c reduction of 1.3%, p=0.05) through Week 52.
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26COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Safety Summary 52-Week Data
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27COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Overview of Treatment Emergent Adverse Events (TEAEs) Through 52 Weeks (Safety Population, N=267) Parameter Arm A icovamenib (N=67) Arm B icovamenib (N=67) Arm C icovamenib (N=67) Combined Arms icovamenib (N=201) Combined Arms placebo (N=66) Patients with ≥1 TEAE, N (%) 19 (28) 22 (33) 14 (21) 55 (27) 18 (27) Treatment-Related SAEs, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) SAEs* , N (%) 1 (1) 0 (0) 1 (1) 2 (1) 1 (1) Treatment Discontinuation due to TEAE, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Study Discontinuation due to TEAE, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Deaths, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Data are n (%) TEAE = Treatment Emergent Adverse event SAE = Serious Adverse Event *Arm A had an SAE of atrial fibrillation. Unrelated to study treatment and occurred during the treatment period. Subject required hospitalization and was discharged in 3 days. Subject continued in the study. *Arm C had an SAE of COVID-19. Unrelated to study treatment and occurred during the treatment period. Subject required hospitalization and was discharged in 3 days. Subject continued in the study. *Placebo Arm had an SAE of nephrolithiasis. Unrelated to study treatment and occurred during the treatment period. Subject required hospitalization and was discharged in 3 days. Subject continued in the study.
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28COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Treatment Emergent Adverse Events (TEAEs) Occurring in ≥5% in Any Study Arm and TEAEs Reported for ALT and/or AST Elevations (Safety Population, N=267) Parameter Arm A icovamenib (N=67) Arm B icovamenib (N=67) Arm C icovamenib (N=67) Combined Arms icovamenib (N=201) Combined Arms placebo (N=66) Diarrhea, N (%) 4 (6) 2 (3) 1 (1) 7 (3) 0 Urinary tract infection, N (%) 0 1 (2) 0 1 (.5) 3 (5) Hyperglycemia, N (%) 2 (3) 5 (7) 1 (1) 8 (4) 3 (5) Headache, N (%) 0 4 (6) 1 (1) 5 (2) 2 (3) ALT increase, N (%) 3 (4) 0 2 (3) 5 (2) 0 AST increase, N (%) 3 (4) 0 1 (1) 4 (2) 0 Data are n (%) of TEAE with ≥5% frequency in any arm and ALT or AST increase irrespective of incidence; Safety population TEAE, treatment-emergent adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase Diarrhea: In the icovamenib arms, all 7 events were Grade 1. Nausea: In the icovamenib arms, 6 of 7 events were Grade 1 and 1 event was Grade 2 (Arm B). In the placebo arm, the 1 event was Grade 1. Hyperglycemia: In the icovamenib arms, 5 of 6 events were Grade 2 and 1 event was Grade 1 (Arm C). In the placebo arm, all 3 events were Grade 2. Headache: In the icovamenib arms, 3 of the 4 events were Grade 1 and 1 event was Grade 2 (Arm B). In the placebo arm, 2 of the 3 events were Grade 1 and 1 event was Grade 2. ALT increase: In the icovamenib arms, 3 of the 4 events were Grade 1 and 1 event was Grade 2 (Arm A). AST increase: In the icovamenib arms, all 3 events were Grade 1.
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29COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Arm A icovamenib (N=67) Arm B icovamenib (N=67) Arm C icovamenib (N=67) Combined Arms icovamenib (N=201) Combined Arms placebo (N=66) Grade 1, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Grade 2, N (%) 0 (0) 1 (1)* 0 (0) 1 (0.5)* 0 (0) Grade 3, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Subjects with Treatment Emergent Adverse Events of Hypoglycemia (Safety Population, N=267) *Hypoglycemic adverse event occurred outside of the 12-week treatment window
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30COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 KEY FINDINGS through 52 Weeks Per Protocol participants taking one or more antihyperglycemic medications at baseline • Continued HbA1c reduction achieved at Week 52 in predefined subset of patients Severe insulin-deficient T2D patients (Arm B) showed the greatest clinically meaningful response (mean HbA1c reduction of 1.5%, p=0.01) through Week 52. • Exposure-response correlation Patients with the greatest exposure achieved the highest reduction in HbA1c. We believe data suggest that a readily achievable exposure level could provide ≥1.5% HbA1c reductions in T2D patients. • GLP-1 failing patients benefited markedly from 12 weeks of icovamenib Patients not achieving HbA1c targets with GLP-1 based therapy showed clinically meaningful responses (HbA1c reduction of 1.3%, p=0.05) through Week 52. • Favorable safety profile Icovamenib was generally well-tolerated, with no adverse-event related discontinuations and no related serious adverse events.
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31COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Key Opinion Leader - Insights Dr. Juan Pablo Frias Chief Medical Officer of Biomea Fusion Ralph DeFronzo, MD Professor of Medicine, Chief of Diabetes Division at the University of Texas Health Science Center at San Antonio and Deputy Director of the Texas Diabetes Institute
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32COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Executive Summary Mick Hitchcock, PhD Interim Chief Executive Officer & Board Member, Biomea Fusion
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33COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Icovamenib in Type 2 Diabetes: 52-Week Highlights in Patients on 1 or more Antihyperglycemic Agent - 9 Months After Last Dose Icovamenib achieved clinically meaningful HbA1c reduction in multiple subgroups Sustained treatment effect in pre-defined severe insulin-deficient patient population Continued benefit observed in severe insulin-deficient diabetes patients Treatment effect in GLP-1 failures also improved and continued Demonstrated marked levels of activity in patients not achieving HbA1c target on GLP-1 therapy at study entry Higher icovamenib exposure led to improved responses PK analysis shows that better HbA1c reductions occurred in patients with better exposure to the drug Favorable safety profile continued Icovamenib was generally well-tolerated, with no adverse-event related discontinuations and no related serious adverse events
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34COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 NEXT STEPS 1. Optimize icovamenib exposure and define dosing criteria with a Food Effect Study (Food Effect Study COVALENT-121 – started 9/11/25; expected completion 12/25) 2. Investigate icovamenib in severe insulin deficient diabetes patients in a Phase IIb Type 2 Diabetes Study (T2D Study COVALENT-211 – initiation expected 4Q 25) 3. Investigate icovamenib in combination with a GLP-1 based therapy in a Phase II Type 2 Diabetes Study (T2D Study COVALENT-212 – initiation expected 4Q 25) 4. Initiate a Phase I with Biomea Fusion's oral GLP-1 RA BMF-650 in obese, otherwise healthy volunteers (Obesity Study GLP-131 – initiation ongoing, expected completion 1H 26)
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35COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Question & Answer Session
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36COVALENT 111 - 52 Week Follow Up Conference Call October 7, 2025 Thank you