BGB-15025 is a potent and selective hematopoietic progenitor kinase 1 (HPK1) inhibitor with biochemical IC50 of 1.04 nM. BGB-15025 shows good selectivity profile among MAP4K family and does not affect ZAP70 phosphorylation up to 1 μM. BGB-15025 potently reduces SLP76 phosphorylation and increase downstream ERK phosphorylation in a concentration dependent manner in T cells-based assay. BGB-15025 induces TCR activation and IL-2 production in T cells. Oral administration of BGB-15025 demonstrates dose-dependent pSLP76 inhibition in splenic T cells and induces serum IL-2 in mouse model. BGB-15025 exhibits anti-tumor activity in GL261 tumor model as single agent, also demonstrated combination effect with anti-PD-1 antibody in CT26 and EMT-6 syngeneic tumor models.
