HM99462

HM99462 is a novel, potent, and orally bioavailable Son of sevenless homolog 1 (SOS1) inhibitor developed by Hanmi Pharmaceutical. It acts by blocking the interaction between SOS1 and KRAS, thereby preventing the activation of KRAS mutations (including KRAS G12C, G12D, G12V, and G13D) and downstream MAPK signaling. In preclinical studies, HM99462 demonstrated robust anti-tumor activity in various KRAS-mutant solid tumor models, both as a monotherapy and in synergistic combination with KRAS G12C, MEK, or EGFR inhibitors. In April 2025, Hanmi Pharmaceutical discontinued the development of HM99462, replacing it with a next-generation SOS1-panKRAS modulator candidate, HM101207, to optimize clinical entry.