- Data demonstrate potent suppression of MAPK signaling and viability in KRAS mutant cell lines, as well as anti-tumor activity across multiple KRASG12D and KRASG12V cell-derived xenograft (CDX) models
- BBO-11818’s selectivity for KRAS demonstrated by its >1000-fold lower potency against NRAS, HRAS, and BRAF-mutant cell lines
- Efficacy of the combination with BBOT’s RAS:PI3K⍺ breaker, BBO-10203, is driven by a robust decrease in tumor cell proliferation and increase in apoptosis; combination benefit also observed with cetuximab and anti-PD-1 treatment
- BBO-11818 is currently being evaluated in the Phase 1 KONQUER-101 trial in patients with KRAS mutant pancreatic, non-small cell lung, and colorectal cancer with initial Phase 1 clinical data expected in the second half of 2026
SOUTH SAN FRANCISCO, Calif., Oct. 23, 2025 (GLOBE NEWSWIRE) -- BridgeBio Oncology Therapeutics, Inc. (“BBOT”) (Nasdaq: BBOT), a clinical-stage biopharmaceutical company focused on RAS-pathway malignancies, today announced new preclinical data on BBO-11818 demonstrating its potential as a potent panKRAS inhibitor targeting mutant KRAS in both the ON (active GTP-bound) and OFF (inactive GDP-bound) 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.
“KRAS is one of the most commonly mutated oncogenes in human cancers, and while current KRASG12C inhibitors have shown promising clinical efficacy, they only address a subset of mutations, leaving many patients without effective options,” said Pedro Beltran, PhD, Chief Scientific Officer of BBOT. “We’ve designed BBO-11818 as a potent panKRAS inhibitor with strong binding affinity for KRAS and broad selectivity over HRAS and NRAS with the goal of achieving high levels of KRAS inhibition in human tumors. The preclinical data presented on BBO-11818 demonstrate potent inhibition of MAPK signaling and viability in KRAS mutant cells, as well as anti-tumor activity across multiple KRASG12D and KRASG12V cell-derived xenograft (CDX) models.”
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 >1000-fold lower potency against NRAS, HRAS, and BRAF-mutant cell lines. Monotherapy results show strong anti-tumor responses, including favorable pharmacokinetics (PK) and oral bioavailability with dose- and time-dependent inhibition of pERK in in vivo pharmacodynamic (PD) 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 robust 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.
“We are pleased to share this updated preclinical data on BBO-11818, which further reinforces its clinical potential,” said Eli Wallace, PhD, Chief Executive Officer of BBOT. “These results support further evaluation of BBO-11818 as a monotherapy and in combination as we continue to drive efforts to deliver meaningful value to patients and work towards fully unlocking the potential of RAS-focused therapies by optimizing target coverage.”
A copy of the poster titled “BBO-11818: an orally bioavailable, highly potent and selective noncovalent pan-KRAS(ON) and (OFF) inhibitor with robust anti-tumor activity in KRAS-mutant preclinical models” will be available on the “Publications” page of the BBOT website following the conference.
About BBO-11818
BBO-11818 is a potent, selective, orally bioavailable non-covalent KRAS inhibitor with activity against multiple KRAS mutants, including KRASG12D and KRASG12V with high selectivity for KRAS over HRAS and NRAS. It targets KRAS in both the ON (active GTP-bound) and OFF (inactive GDP-bound) states, potently suppressing MAPK signaling and inhibiting cell proliferation in KRAS mutant cell lines. BBO-11818 is currently being evaluated in the Phase 1 KONQUER-101 trial in patients with KRAS mutant pancreatic, non-small cell lung, and colorectal cancer, KRASG12A, KRASG12C, KRASG12D, KRASG12S, or KRASG12V mutations, or KRAS amplification. Initial Phase 1 clinical data are expected in the second half of 2026.
About BBOT
BBOT is a clinical-stage biopharmaceutical company advancing a next-generation pipeline of novel small molecule therapeutics targeting RAS and PI3Kα malignancies. BBOT has the goal of improving outcomes for patients with cancers driven by the two most prevalent oncogenes in human tumors. For more information, please visit www.bbotx.com and follow us on LinkedIn.
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