91-LB: COVALENT-111, a Phase 1/2 Trial of BMF-219, a Covalent Menin Inhibitor, in Patients with Type 2 Diabetes Mellitus—Preliminary Results

Abstract

Type 2 Diabetes Mellitus (T2DM) is characterized by impaired glycemic control caused by insulin resistance and progressive beta cell failure. Menin, a scaffold protein, drives beta cell proliferation when inhibited. We have reported BMF-219, an oral covalent menin inhibitor, elicits durable glycemic control following a short treatment in a ZDF Rat model. COVALENT-111, a randomized, double-blind, placebo-controlled study is evaluating BMF-219 in healthy adults and adults with T2DM diagnosed ≤15 yrs (NCT05731544). Here we report initial results from the first cohort of T2DM patients treated with BMF-219. Patients with poor glycemic control (HbA1C ≥7%) on their current antidiabetic regimen were enrolled. Twelve patients were randomized 5:1 (10 BMF-219, 2 placebo) to receive 100 mg QD for 4 weeks while continuing their existing treatment. BMF-219 was well tolerated; no subjects discontinued treatment or exited the trial during the 4-week treatment and all subjects continue in follow-up to assess durability of the treatment effect. There were no dose reductions, SAEs, or severe AEs. All TRAEs were mild and observed in 3 of 12 subjects. No subjects showed symptomatic hypoglycemia. These data demonstrate preliminary proof of concept for the novel disease-modifying effect of BMF-219 in T2DM. Enrollment is ongoing at higher doses; additional follow-up data will be presented. Disclosure J. E. Rodriguez: None. A. Abitbol: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Dexcom, Inc., Novo Nordisk Canada Inc., Janssen Pharmaceuticals, Inc., Research Support; Abbott Diabetes, Lilly Diabetes, Zucara Therapeutics, Novo Nordisk Canada Inc., Moderna, Inc., Senseonics, Speaker's Bureau; Boehringer Ingelheim (Canada) Ltd., Lilly Diabetes, Amgen Canada, Dexcom, Inc., Novo Nordisk Canada Inc., HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi. F. Abuzgaya: None. C. Perez: None. S. Mourya: Employee; Biomea Fusion, Inc. B. Munneke: Employee; Biomea Fusion, Inc., Corvus Pharmaceuticals. S. W. Morris: Employee; Biomea Fusion, Inc. T. Butler: Board Member; Biomea Fusion, Inc., Employee; Biomea Fusion, Inc., Stock/Shareholder; Biomea Fusion, Inc. Funding Not applicable