FLT3 is a receptor tyrosine kinase (RTK) that plays a central role in the survival, proliferation, and differentiation of immature blood cells. Notably, FLT3 gene mutations are common in patients with AML and are associated with a poor prognosis. While FLT3-specific and pan-tyrosine kinase inhibitors are approved by the FDA across various lines of therapy in AML, these agents have produced relatively low rates of durable responses and overall survival remains an unmet need.
In preclinical study, BMF-500 demonstrated multi-fold higher potency and increased cytotoxicity than commercially available non-covalent FLT3 inhibitor as well as the potential utility of combination strategies to achieve higher cell killing with reduced concentrations of BMF-500 and BMF-219 (oral investigational covalent menin inhibitor) (Law et al. ASH 2022; Law et al. AACR 2023). These data provide preclinical evidence for combining pathway-specific inhibitors as a promising therapeutic strategy for further investigation in acute leukemia.