845-P: The Menin Inhibitor Ziftomenib Induces Insulin Production and Improves Insulin Sensitivity in a Rat Model of Type 2 Diabetes Mellitus (T2DM)

Menin is an epigenetic scaffold protein known to regulate pathogenic gene expression in several cell types. Genetic menin loss (MEN1 Syndrome) is associated with insulinemia due to upregulated pancreatic β-cell proliferation. Ziftomenib is a potent and selective menin inhibitor currently in clinical trials for the treatment of acute leukemias. Zucker Diabetic Fatty rats were used to assess the antidiabetic activity of ziftomenib dosed orally once daily for 27 days. Ziftomenib treatment was well tolerated and rapidly reduced fasting blood glucose (FBG) levels, with normalization of FBG levels observed in most animals within 2 weeks. Ziftomenib also progressively reduced %HbA1C by an average of 1.49% by week 4 (FIG). Oral glucose tolerance tests demonstrated that ziftomenib-treated animals achieved significantly improved postprandial glucose control (P