BBO-11818 + BBO-10203

BBO-11818 + BBO-10203 is an investigational, all-oral combination of two small-molecule drug candidates developed by BridgeBio Oncology Therapeutics (BBOT). BBO-11818 is a first-in-class, non-covalent pan-KRAS inhibitor that targets mutant KRAS in both its active (ON) and inactive (OFF) states, with high affinity for KRAS G12D and G12V mutants. BBO-10203 is a first-in-class RAS:PI3Kα 'breaker' that covalently binds to the RAS-binding domain of PI3Kα, blocking KRAS, HRAS, and NRAS from activating downstream PI3Kα-AKT signaling without directly inhibiting PI3Kα kinase activity, thereby avoiding hyperglycemia. The combination is designed to simultaneously suppress the MAPK and PI3Kα pathways, countering PI3Kα-mediated resistance to KRAS inhibition. It is currently being evaluated in Phase 1 clinical trials (such as the KONQUER-101 study) for patients with advanced KRAS-mutant solid tumors, including colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and non-small cell lung cancer (NSCLC).