BridgeBio’s BBO-11818 Drives Complete Tumor Regressions in KRASG12D/V Models
BridgeBio Oncology Therapeutics’ BBO-11818, a non-covalent pan-KRAS inhibitor, suppressed MAPK signaling and inhibited proliferation across KRASG12D and G12V models, driving potent tumor regressions. Monotherapy and combinations with BBO-10203, cetuximab and anti-PD-1 yielded complete regressions, supporting clinical Phase 1 data due H2 2026.
1. Preclinical Efficacy Highlights
BBO-11818 potently inhibited ERK phosphorylation and MAPK signaling, leading to reduced proliferation in KRAS-mutant cell lines. In vivo, the inhibitor produced robust tumor regressions in KRASG12D and KRASG12V cell-derived xenograft models, demonstrating broad activity across key KRAS variants.
2. Combination Therapy Synergy
Combination studies showed that BBO-11818 paired with BBO-10203 or cetuximab enhanced anti-tumor effects in both CDX and PDX models. In the CT26 syngeneic model, adding anti-PD-1 induced complete tumor regressions and an adaptive immune response, underscoring its potential as a combination backbone.
3. Mechanism of Action
BBO-11818 is a selective, orally bioavailable non-covalent inhibitor that binds KRAS in both active GTP-bound and inactive GDP-bound states. It exhibits high selectivity over HRAS and NRAS while potently suppressing MAPK signaling and blocking cell proliferation.
4. Clinical Development Timeline
BBO-11818 is currently in the Phase 1 KONQUER-101 trial enrolling patients with locally advanced or metastatic KRAS-mutant solid tumors. Updated clinical data are expected in the second half of 2026, marking a key upcoming milestone for the program.