Biomea Fusion, Inc. · NASDAQ:BMEA

Biomea Fusion — American Diabetes Association (ADA) 2025 Scientific Sessions

20 slides from Biomea Fusion's conference presentation, June 2025

  1. Slide 1: COVALENT-111: 26-Week Efficacy and Safety of Daily Oral Icovamenib

    COVALENT-111: 26-Week Efficacy and Safety after 8 and 12 Weeks of Daily Oral Icovamenib in Patients with Poorly Controlled Type 2 Diabetes Juan Pablo Frías, MD Chief Medical Officer Biomea Fusion, Inc. San Carlos, CA, USA

  2. Slide 2: Disclosures and Photography Allowed

    No, Nothing to disclose X Yes, please specify disclosures Consulting / Other Honoraria / Funded Royalties / Stock Ownership / Company / Name Advisory Employee (Please Expense Research Patent Options Equity Position Board specify) Biomea Fusion X PHOTOGRAPHY ALLOWED You may take photos of this presen

  3. Slide 3: Background: Menin and Icovamenib

    Background The scaffold protein menin and icovamenib, an oral covalent menin inhibitor Menin • Nuclear scaffold protein that plays a physiological role in glucose homeostasis1 • Inhibition of menin enhances beta-cell proliferation and increased GLP-1 receptor expression2 Icovamenib Icovamenib Key Ch

  4. Slide 4: Icovamenib's Dual Mechanism of Action in Human Islets

    Background Icovamenib’s dual mechanism of action assessed in human islets Dose-dependent increase in GSIS with Glucose-dependent increase in beta-cell proliferation icovamenib + tirzepatide vs tirzepatide alone Proliferating beta cells as a fraction of total beta cells GSIS (-/+ tirzepatide) (GSIS)

  5. Slide 5: T2D Is a Heterogeneous Disease

    Background T2D is a heterogeneous disease – two core pathophysiologic drivers INSULIN-DEFICIENT DIABETES INSULIN RESISTANT DIABETES Severe insulin- Mild age-related Mild obesity- Severe insulin deficient diabetes related resistant diabetes (MARD) diabetes diabetes (SIDD) (MOD) (SIRD) 18% 39% 22% 15%

  6. Slide 6: COVALENT-111 Study Objective and Definitions

    COVALENT 111 | Study Objective and Definitions Primary Objective Primary Endpoint To assess the effect on glycemic control Change in HbA1c from baseline at Week 26 Study Population Per protocol (PP) population includes placebo and active participants who received at least 80% of their total dose1 St

  7. Slide 7: Trial Design

    Trial Design Phase 2a randomized, double-blind, placebo-controlled study in participants with T2D Eligibility Criteria • Adults (18-65 yo) with T2D (<7 yrs) • 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 ra

  8. Slide 8: Baseline Demographics and Characteristics

    Baseline Demographics and Characteristics Arm A Arm B Arm C Combined Arms Combined Arms Parameter icovamenib icovamenib icovamenib icovamenib Placebo Mean (SD) or % (N=51) (N=41) (N=36) (N=128) (N=57) Age (yr) 55 (7) 56 (6) 52 (10) 54 (8) 54 (8) Duration of T2D Diagnosis (yr) 4.1 (1.9) 4.6 (1.9) 4.1

  9. Slide 9: Baseline Antihyperglycemic Agents

    Baseline Antihyperglycemic Agents Arm A Arm B Arm C Combined Arms Combined Arms Parameter icovamenib icovamenib icovamenib icovamenib Placebo n (%) (N=51) (N=41) (N=36) (N=128) (N=57) Number of T2D Medications 0 6 (12) 4 (10) 3 (8) 13 (10) 7 (12) 1 39 (76) 23 (56) 23 (64) 85 (66) 41 (72) 2 4 (8) 11

  10. Slide 10: T2D Subtype at Baseline

    T2D Subtype at Baseline Arm A Arm B Arm C Combined Arms Combined Arms Parameter icovamenib icovamenib icovamenib icovamenib Placebo n (%) (N=51) (N=41) (N=36) (N=128) (N=57) SIDD 14 (27) 9 (22) 6 (17) 29 (23) 14 (25) MARD 13 (25) 7 (17) 6 (17) 26 (20) 10 (18) MOD 21 (41) 21 (51) 23 (64) 65 (51) 29 (

  11. Slide 11: Mean Change in HbA1c from Baseline at Week 26

    Mean Change in HbA1c from Baseline at Week 26 Per Protocol Population, by study arm Mean Change in HbA1c Over Time (n=128 Active; n=57 Placebo) 0.00 Arm A (N=51) Arm B (N=41) Mean Change HbA1c (%) Arm C (N=36) -0.25 P=0.229 Pooled Placebo (N=57) P=0.396 -0.50 P=0.048* -0.75 Icovamenib Icovamenib Tr

  12. Slide 12: Mean Change in HbA1c in Participants with SIDD

    Mean Change in HbA1c from Baseline to Week 26 in Participants with SIDD Per Protocol Population – SIDD by study arm Arm A, B, and C (n=29 Active; n=14 Placebo) Arm B (n=9 Active; n=14 Placebo) 0.2 0.2 0 0 -0.2 -0.2 Mean Change HbA1c (%) Mean Change HbA1c (%) -0.4 -0.4 -0.6 -0.6 -0.8 -0.8 Placebo Pla

  13. Slide 13: SIDD Participants Had Lowest Baseline C-peptide Index

    Participants with SIDD had the Lowest Baseline Insulin Production as Measured by the C-peptide Index During a 2-hr OGTT C-peptide Index at Baseline • The C-peptide Index is a well-validated measure of beta-cell function • As expected, the lowest insulin production occurred in participants with Sever

  14. Slide 14: Icovamenib Increased Insulin Secretion in Insulin-Deficient T2D

    Icovamenib Increased Insulin Secretion (measured by C-peptide) in Insulin-Deficient but not in Insulin-Resistant T2D SIDD MARD Treatment Period Treatment Period Insulin-Deficient participants demonstrated an increase in C-peptide over time N=43 N=36 MOD SIRD Treatment Period Treatment Period Insulin

  15. Slide 15: Icovamenib Increased Insulin Secretion as Measured by C-peptide

    Icovamenib Increased Insulin Secretion as Measured by C-peptide At Week 26, 55% increase in insulin secretion, with over half the increase occurring while off icovamenib Participants with Severe Insulin-Deficient Diabetes C-peptide Index Change from Baseline During OGTT 55% mean increase in C-peptid

  16. Slide 16: Change in C-peptide Index versus HbA1c at Week 26

    Change from Baseline at Week 26 in C-peptide Index versus HbA1c Icovamenib-treated participants with SIDD Reduction in HbA1c correlated significantly with an increase in insulin secretion (C-peptide index), validating the mechanism of action of icovamenib C-peptide Index (CPI) = 104 x Mean AUC C-pep

  17. Slide 17: Change in HbA1c in Participants Taking GLP1-RA at Baseline

    Change in HbA1c from Baseline to Week 26 in participants taking GLP1-RA at Baseline Participants treated with GLP1-RA at baseline across all arms (N=10) GLP-1-Based Medicine 0 Placebo-adjusted Mean Change HbA1c (%) -0.2 • ~1.0% reduction in HbA1c with icovamenib as add-on to “failing” GLP-1 RA-based

  18. Slide 18: Overview of Treatment Emergent Adverse Events Through 26 Weeks

    Overview of Treatment Emergent Adverse Events Through 26 Weeks (Safety Population, N=267) Arm A Arm B Arm C Combined Arms Combined Arms Parameter icovamenib icovamenib icovamenib icovamenib placebo (N=67) (N=66) (N=67) (N=200) (N=67) Participants with ≥1 TEAE 18 (27) 20 (30) 14 (21) 52 (26) 19 (28)

  19. Slide 19: Summary and Conclusions

    Summary and Conclusions 12 weeks of icovamenib therapy resulted in clinically and statistically significant improvements in HbA1c at Week 26 (14 weeks after final dose) Improvements in glycemic control were greatest in participants with severe insulin-deficient diabetes (SIDD) Participants with SIDD

  20. Slide 20: Thank you

    biomea FUSION’ Thank you

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