Background and Aims: Inhibition of menin, a scaffold protein, results in beta cell proliferation and enhanced insulin secretion in T1D. BMF-219, an oral covalent menin inhibitor, is in clinical development for T1D and T2D. Based on ex-vivo islet microtissue data and preclinical animal models, we hypothesize BMF-219 treatment will result in beta-cell proliferation and improved insulin secretory capacity. Here we describe the design of the COVALENT-112, a Phase II trial assessing BMF-219 in adults with T1D (NCT06152042).
Methods: COVALENT-112 consists of two parts. Part A is a single-arm, open-label study; Part B is a randomized, double-blind, placebo-controlled study. Both are enrolling adults with Stage 3 T1D (HbA1c 6.5-10.0%). Part A is enrolling participants into 2 cohorts: 1) diagnosed ≤3 years with C-peptide ≥0.2 nmol/L (n=20); 2) diagnosed 3 to 15 years with C-peptide ≥0.08 nmol/L (n=20). In each cohort, 10 participants will be treated with BMF-219 100mg once daily (QD) and 10 will be treated with 200mg QD as an adjunct to insulin therapy. Part B is a 3-arm study assessing BMF-219 100mg QD, 200mg QD, or placebo for 12 weeks in participants with a diagnosis of T1D ≤3 years and C-peptide ≥0.2 nmol/L. In both Parts A and B, BMF-219 treatment duration will be 12 weeks, with a 40-week follow-up (52 weeks total). Key endpoints include change from baseline in stimulated C-peptide, insulin dose, and HbA1c. CGM will be utilized frequently, and safety, including hypoglycemia, will be assessed throughout the 52-week trial.
Results: Initial results of the open-label study are expected in 2024; results of the double-blind, placebo-controlled study are expected in 2025. COVALENT-112 study is ongoing in the US and Canada.
Conclusions: BMF-219 is a novel oral covalent menin inhibitor. In preclinical studies, it has demonstrated beta cell proliferation. COVALENT-112 assesses the efficacy and safety of 12-week QD BMF-219 in Stage 3 T1D, potentially addressing an important unmet need in this patient population.
H.T. Tran: None. D. Katselnik: None. D.S. Denham: None. M.K. Stevens-Brogan: None. C.W. Decker: None. S. Mourya: None. J.P. Frias: Research Support; Akero Therapeutics, Inc. Consultant; Akero Therapeutics, Inc. Research Support; Altimmune Inc. Consultant; Altimmune Inc. Research Support; Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim. Research Support; 89bio, Inc. Consultant; 89bio, Inc. Research Support; Eli Lilly and Company. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Merck & Co., Inc. Consultant; Merck & Co., Inc. Research Support; Novartis Pharmaceuticals Corporation. Consultant; Novartis Pharmaceuticals Corporation, Novo Nordisk. Board Member; Novo Nordisk. Research Support; Novo Nordisk, Pfizer Inc. Consultant; Pfizer Inc. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Stock/Shareholder; Biomea Fusion, Inc. Employee; Biomea Fusion, Inc. T. Butler: Employee; Biomea Fusion, Inc. Board Member; Biomea Fusion, Inc. C.B. Guzman: None.
