BBOT Presents Preclinical Data Demonstrating Potential of BBO-11818 as a Potent panKRAS Inhibitor at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

Core Insights - BridgeBio Oncology Therapeutics, Inc. (BBOT) announced new preclinical data on BBO-11818, a potent panKRAS inhibitor targeting mutant KRAS in both active and inactive states, with selectivity over HRAS and NRAS [1][2][4] Group 1: Preclinical Data and Efficacy - BBO-11818 demonstrates potent inhibition of MAPK signaling and cell viability in KRAS mutant cells, with single-digit nanomolar EC50 values observed [2][5] - The selectivity of BBO-11818 for KRAS is highlighted by its over 1000-fold lower potency against NRAS, HRAS, and BRAF-mutant cell lines [5] - Monotherapy with BBO-11818 shows strong anti-tumor responses and favorable pharmacokinetics, with dose- and time-dependent inhibition of pERK in in vivo studies [2][5] Group 2: Combination Treatments - Combination treatment with BBOT's RAS:PI3Kα breaker, BBO-10203, and cetuximab enhances anti-tumor activity in vitro and in CDX models [2][5] - The combination efficacy is driven by a significant decrease in tumor cell proliferation and an increase in apoptosis [5] - BBO-11818 also shows a combination benefit with anti-PD-1 treatment, resulting in complete tumor regressions in specific mouse models [2][5] Group 3: Clinical Development - BBO-11818 is currently being evaluated in the Phase 1 KONQUER-101 trial for patients with KRAS mutant pancreatic, non-small cell lung, and colorectal cancer [5][6] - Initial Phase 1 clinical data is expected in the second half of 2026 [5][6] Group 4: Company Overview - BBOT is a clinical-stage biopharmaceutical company focused on developing novel small molecule therapeutics targeting RAS and PI3Kα malignancies [7] - The company aims to improve outcomes for patients with cancers driven by prevalent oncogenes [7]