お知らせ • Mar 07
Bridgebio Oncology Therapeutics, Inc. Announces Publication in Cancer Discovery Highlighting Preclinical Data Demonstrating BBO-11818 is Potent and Selective panKRAS Inhibitor
BridgeBio Oncology Therapeutics, Inc. announced the publication of preclinical data describing the discovery and characterization of BBO-11818, a panKRAS inhibitor targeting KRAS in both the ON and OFF states, with significant therapeutic potential for patients with KRAS mutant cancers. BBO-11818 is a selective, orally bioavailable non-covalent inhibitor that targets KRAS in both the ON and OFF states, has high selectivity over HRAS and NRAS, and displays strong activity in KRAS mutant preclinical models, including KRASG12D and KRASG12V. BBO-11818 showed significant tumor growth inhibition across multiple tumor types in preclinical models and demonstrated enhanced efficacy in combination with other anti-tumor agents, including BBO-10203, BBOT’s selective RAS:PI3Ka breaker. Preliminary clinical data from the BBO-11818 Phase 1 KONQUER-101 trial showed encouraging anti-tumor activities and differentiated safety, with additional data expected in the second half of 2026; internal combination with BBO-10203 is anticipated to open later in 2026. The publication, titled “Discovery of BBO-11818, a Potent and Selective Non-covalent Inhibitor of (ON) and (OFF) KRAS with Activity Against Multiple Oncogenic Mutants” was published in the peer-reviewed journal Cancer Discovery, a journal of the American Association for Cancer Research’s (AACR). The preclinical findings in this publication highlight the key properties BBO-11818 and its potential to address critical limitations associated with other compounds targeting mutant KRAS. Unlike several existing inhibitors that primarily target the inactive GDP-bound state, BBO-11818 potently binds and inhibits KRAS in both its ON and OFF states, as demonstrated through structural analysis, surface plasmon resonance, and functional assays. By targeting the active state of KRAS, BBO-11818 may overcome a critical resistance mechanism observed with current KRAS inhibitors, in which tumors upregulate KRAS expression or activate upstream signaling to sustain pathway activation. Data demonstrate potent activity against multiple clinically relevant KRAS mutants, including KRASG12D, KRASG12V, and KRASG12C, with high selectivity for KRAS, exhibiting >500-fold selectivity over other RAS isoforms. BBO-11818’s activity across a broad range of KRAS mutants is designed to help prevent the emergence of resistance driven by secondary activating KRAS mutations that can limit the efficacy of allele-specific inhibitors. In addition, its high specificity for KRAS may support improved tolerability and greater potential for combination with other therapeutic agents. Monotherapy studies show robust anti-tumor activity across multiple in vitro and in vivo models of KRAS mutant solid tumors, including colorectal, pancreatic, and lung cancers. BBO-11818 also demonstrated strong combination potential with immune checkpoint inhibitors, anti-EGFR antibodies, and BBO-10203, the company’s RAS:PI3Ka breaker compound. BBO-11818 is currently being evaluated in the Phase 1 KONQUER-101 trial (NCT06917079) in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors. Initial Phase 1 monotherapy data were announced in January 2026, demonstrating encouraging early anti-tumor activity across dose levels and tumor types, including a confirmed partial response in a patient with pancreatic ductal adenocarcinoma (PDAC) with a 56% tumor reduction. The company plans to provide additional data updates in the second half of 2026 and to study the combination of BBO-11818 with BBO-10203 later in 2026. The discovery and preclinical characterization of BBO-11818 is the result of a collaborative effort between BBOT, the RAS Initiative at Frederick National Laboratory, and Lawrence Livermore National Laboratory. BBO-11818 is a selective, orally bioavailable non-covalent inhibitor that targets KRAS in both the ON and OFF states, has high selectivity over HRAS and NRAS, and displays strong activity in KRAS mutant preclinical models, including KRASG12D and KRASG12V. In addition, it potently suppresses 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 subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors.