Menin is an epigenetic regulatory protein that plays a key role in beta-cell proliferation and function, as previously demonstrated though increased beta-cell mass generation in Men1 knockout mice (Ja et al., 2021;13 (5) :e13524) . Here, we demonstrate the marked potential of an oral menin inhibitor, BMF-219, in durable glycemic control following a short course treatment in a Type 2 Diabetes Mellitus (T2DM) Zucker Diabetic Fatty Rat model. Rats were treated daily with BMF-219, liraglutide or vehicle for 28 days and monitored for an additional 28 days post-treatment. All animals tolerated BMF-219 well throughout the study. Notably, BMF-219 treatment resulted in a significant reduction in HbA1C at Day 21, which reached 3.5% absolute reduction in HbA1C versus vehicle, compared to liraglutide (1.7% reduction) at Day 29 and remained reduced throughout the entire study, including post-treatment. The high-dose arm of BMF-219 showed a strong reduction in 4-hour fasting blood glucose during the treatment up to Day 29. Both BMF-219 dose groups showed improved glycemic control by oral glucose tolerance test (OGTT) on day 25, in contrast to vehicle and liraglutide-treated animals. Additionally, insulin levels, HOMA-IR, HOMA-B, OGTT, HbA1C, and C-peptide levels measured at Day 57 across all groups will be reported. Collectively, these data demonstrate the novel long-acting potential of BMF-219 as an oral treatment for T2DM, in maintaining glycemic control after short-term dosing.
P. Somanath: Employee; Biomea Fusion, Inc., Stock/Shareholder; Biomea Fusion, Inc. M. Balakrishnan: Employee; Biomea Fusion, Inc., Other Relationship; Gilead Sciences, Inc., Stock/Shareholder; Biomea Fusion, Inc., Gilead Sciences, Inc. T. Butler: Employee; Biomea Fusion Inc. S. Mourya: Employee; Biomea Fusion, Stock/Shareholder; Ascendis Pharma A/S. W. Li: None. T. C. Archer: Employee; Biomea Fusion. B. Law: Stock/Shareholder; Biomea Fusion Inc., Mirum Pharmaceuticals. D. Lu: Employee; Biomea Fusion Inc., Stock/Shareholder; AbbVie Inc. T. Rughwani: None. L. Kumar: None. T. Kinoshita: None.