BBO-11818

BBO-11818 is an orally bioavailable small molecule pan-KRAS dual inhibitor developed by BridgeBio Oncology Therapeutics, a subsidiary of BridgeBio Pharma. It is designed to directly and non-covalently bind both the inactive GDP-bound “OFF” and active GTP-bound “ON” states of KRAS, with high potency against the G12D and G12V mutants. This dual-binding mechanism differentiates BBO-11818 from first-generation KRAS inhibitors that typically target only one state (usually the inactive form), potentially overcoming resistance mechanisms seen in current therapies. Preclinical data show sub-nanomolar to single-digit nanomolar potency for pERK inhibition in KRAS G12D and G12V-mutant cell lines, as well as activity against KRAS G12C-mutant lines. The compound demonstrates over 500-fold selectivity for KRAS over H-RAS and NRAS, with little effect on NRAS or BRAF mutant cell lines. BBO-11818 is currently being evaluated in Phase I clinical trials (KONQUER-101) for advanced solid tumors driven by mutant KRAS[1][2][4][5][6].

Other names

pan-KRAS inhibitor - BridgeBio Pharma