BH-30236 + venetoclax

BH-30236 + venetoclax is an investigational combination therapy being developed by BlossomHill Therapeutics for the treatment of relapsed or refractory acute myeloid leukemia (R/R AML) and higher-risk myelodysplastic syndrome (HR-MDS). BH-30236 is a novel, orally bioavailable, macrocyclic small molecule inhibitor that targets CDC-like kinases (CLK), as well as PIM3, FLT3, and DYRK1/2. It works by modulating aberrant alternative RNA splicing, specifically suppressing SRSF phosphorylation and inducing splicing alterations that promote apoptosis. Preclinical data suggests that BH-30236 downregulates anti-apoptotic proteins such as MCL-1, which often mediates resistance to BCL-2 inhibitors. Venetoclax is a selective BCL-2 inhibitor. The combination of BH-30236 and venetoclax aims to provide synergistic anti-tumor activity by simultaneously inhibiting multiple survival pathways and is currently being evaluated in a Phase 1/1b dose-escalation study.