BridgeBio Oncology announces new preclinical data on BBO-11818 study

BridgeBio Oncology (BBOT) announced new preclinical data on BBO-11818 demonstrating its potential as a potent panKRAS inhibitor targeting mutant KRAS in both the ON and OFF states, with selectivity over HRAS and NRAS. The data were presented at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. In these preclinical findings, cell-based assays confirm BBO-11818 potently inhibits ERK phosphorylation and proliferation in KRAS mutant cell lines with single-digit nanomolar EC50 values observed. The selectivity of BBO-11818 for KRAS is demonstrated by its greater than1000-fold lower potency against NRAS, HRAS, and BRAF-mutant cell lines. Monotherapy results show strong anti-tumor responses, including favorable pharmacokinetics and oral bioavailability with dose- and time-dependent inhibition of pERK in in vivo pharmacodynamic studies, as well as regressions at well-tolerated doses in CDX models of KRAS mutant pancreatic, non-small cell lung, and colorectal cancer. Combination treatment with BBO-10203, BBOT’s selective RAS:PI3K breaker that blocks RAS-mediated activation of the PI3K-AKT pathway, and cetuximab, an approved anti-EGFR monoclonal antibody, demonstrated enhanced anti-tumor activity both in vitro and in CDX models. Importantly, the efficacy of the BBO-11818 + BB0-10203 combination is driven by a decrease in tumor cell proliferation and increase in apoptosis. BBO-11818 also showed a combination benefit with anti-PD-1 treatment resulting in complete tumor regressions in the KRASG12D CT26 syngeneic tumor mouse model.