BridgeBio Oncology’s BBO-11818 Shows >500-Fold KRAS Selectivity and 56% Tumor Reduction
BBO-11818, a non-covalent oral pan-KRAS inhibitor, demonstrated potent inhibition of KRASG12D and G12V with >500-fold selectivity over HRAS and NRAS and significant tumor suppression across colorectal and pancreatic models. Early Phase 1 KONQUER-101 data showed a 56% tumor reduction in a PDAC patient, with BBO-10203 combination trials planned late 2026.
1. Preclinical Discovery and Selectivity
BBO-11818 is a non-covalent, orally bioavailable inhibitor designed to target KRAS in both ON and OFF states, demonstrating >500-fold selectivity over HRAS and NRAS. Structural analysis and functional assays confirmed potent binding to KRASG12D and G12V mutants.
2. In Vivo Efficacy and Combination Potential
Monotherapy studies showed significant tumor growth inhibition in colorectal, pancreatic and lung cancer models, while combination studies highlighted enhanced efficacy with immune checkpoint inhibitors, anti-EGFR antibodies and the RAS:PI3Kα breaker BBO-10203.
3. Early Phase 1 Clinical Results
The ongoing Phase 1 KONQUER-101 trial reported a confirmed partial response in a pancreatic ductal adenocarcinoma patient, achieving a 56% tumor reduction and demonstrating a differentiated safety profile across dose levels.
4. Future Clinical Plans
BBOT plans to present additional monotherapy and combination data in the second half of 2026 and will initiate an internal BBO-11818 and BBO-10203 combination cohort later in 2026 to explore synergistic effects.