BLU-2069

BLU-2069 is a potent, selective, and orally bioavailable small molecule inhibitor of Hematopoietic Progenitor Kinase 1 (HPK1, also known as MAP4K1), developed by Blueprint Medicines in collaboration with Roche. HPK1 is a serine/threonine kinase that negatively regulates T cell receptor (TCR) signaling. By inhibiting HPK1, BLU-2069 enhances immune cell activation, increases cytokine secretion (such as IL-2 and IFNγ), and promotes anti-tumor immunity. In preclinical models, it has demonstrated efficacy both as a monotherapy and in combination with PD-L1 checkpoint inhibitors, leading to increased intratumoral CD8+ T cell infiltration and improved effector phenotypes.