Biomea Fusion announces data from ongoing Phase II study of BMF-219

Biomea Fusion announced initial positive topline data for the first two cohorts of patients with type 2 diabetes mellitus enrolled in the Phase II portion of its ongoing Phase I/II clinical study of BMF-219, the company’s novel, investigational covalent menin inhibitor. Beta cell loss has been observed to be a critical component of the etiology and pathogenesis of both type 2 and type 1 diabetes; menin is thought to be a key inhibitory regulator that limits beta cell recovery in the pancreas. Using its proprietary FUSION System, Biomea designed BMF-219 to specifically inhibit menin to release the brakes on beta cells, and potentially enable their regeneration, reactivation, and preservation. This is the first clinical observation of patients with diabetes having a robust glucose-lowering response driven by an investigational menin inhibitor with a potentially disease-modifying mechanism of action, which may allow for continued glycemic control for prolonged periods even after treatment is stopped. 40 patients were enrolled in the first three cohorts of COVALENT-111, with the first cohort comprising 16 healthy volunteers; 12 HVs were exposed to 100 mg BMF-219 once daily for two weeks and 4 HVs were exposed to placebo. In Cohorts 2 and 3, T2DM patients received BMF-219 once daily for 4 weeks with or without food, respectively. In the two active treatment cohorts, enrolled patients had T2DM diagnosed for less than15 years, were between the ages of 18 to 65, had been treated with lifestyle management together with up to three anti-diabetic medications, with a stable dose for at least two months prior to screening, had a BMI greater than or equal to25 and less than or equal to40 kg/m2, and had poorly controlled diabetes. At baseline, diabetic patients enrolled in the two active treatment cohorts, Cohorts 2 and 3, had a median A1c of 7.9 and 7.8%, respectively. A negative food effect was seen between active treatment Cohort 3 and Cohort 2, which decreased the exposure significantly. Patients in active treatment Cohort 3 saw about a three-fold median increase in Cmax and AUC compared to Cohort 2. Additional Clinical Observations: Cohort 3: Patients on BMF-219 demonstrated a median A1c reduction: -1.0% and an 89% response rate at 4 weeks; 78% of patients achieved a greater than0.5% reduction in A1c; 56% achieved a greater than1.0% reduction in A1c; Cohort 2: Patients on BMF-219 had a median A1c reduction: -0.3% and a 70% response rate at 4 weeks; 30% of patients achieved a greater than0.5% to less than1.0% reduction in A1c; Placebo: 4 diabetic patients on placebo had a median A1c and mean A1c reduction between -0.1% to -0.15%. In COVALENT-111 all patients are being assessed for changes in plasma glucose, HOMA-B, HOMA-IR, C-peptide, fasting insulin, oral glucose tolerance testing, key metabolic and lipid parameters, including weight, triglycerides, cholesterol, and for durability of response after BMF-219 treatment has completed. Further analysis and a detailed data summary will be presented at an upcoming major medical meeting. BMF-219 was generally well tolerated; all patients completed the 4-week treatment, and all patients continue in follow-up to assess the durability of the treatment effect. There were no dose reductions, serious adverse events, or severe adverse events. In the active treatment Cohorts 2 and 3 7 of 20 patients treated with BMF-219 showed mild Treatment Emergent AEs, 1 of 20 patients treated with BMF-219 showed a moderate TEAE and 2 of 4 patients treated with placebo showed mild TEAEs. No patients showed symptomatic hypoglycemia and no other TEAEs were observed. In the healthy volunteer Cohort 1, 2 of 12 subjects treated with BMF-219 and 1 of 4 subjects treated with placebo showed mild TEAEs. No other TEAEs were observed.