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]

Icovamenib Program - Icovamenib, a menin inhibitor, demonstrates significant and durable HbA1c reductions, up to approximately 1.5%, sustained well beyond the end of treatment[5] - In a Phase 2a study (COVALENT-111), a 12-week oral dosing of Icovamenib led to a placebo-adjusted HbA1c reduction of 1.5% (p=0.02) at Week 26 in patients with severe insulin-deficient diabetes[71] - At Week 26, patients with Severe Insulin-Deficient Diabetes (SIDD) showed a 53% mean increase in C-peptide levels after Icovamenib treatment[60] - Icovamenib has a $6 billion+ estimated U S revenue potential based on 10% penetration at $10,000 per year in the target T2D patients[7, 15] BMF-650 Program - BMF-650, an oral GLP-1 RA, is built on a similar scaffold as orforglipron, aiming for best-in-class status with an optimized exposure profile[7] - Preclinical studies of BMF-650 showed approximately 2 to 3-fold greater oral bioavailability compared to orforglipron[100] - In obese cynomolgus monkeys, BMF-650 demonstrated meaningful appetite suppression over a 6-day treatment period[110, 112] - In a weight loss study in obese cynomolgus monkeys, BMF-650 at 30 mg/kg resulted in a 15.2% average weight reduction from baseline over 28 days[126, 133] Financials and Milestones - For the three months ended March 31, 2025, Biomea Fusion reported a net loss of $29.262 million, or $0.80 per share[139] - As of March 31, 2025, Biomea Fusion had $36.2 million in cash, cash equivalents, and restricted cash[139]