BH-501242 / BlossomHill Therap - LARVOL DELTA

Design and discovery of BH-501242, a novel pan-KRAS on/off inhibitor targeting KRAS switch II pocket (AACR 2026) - "MRTX1133 was the first to demonstrate low single-digit nM cell potency for G12D mutation; however, the inhibitor lacked the ADME properties required for a successful oral drug...Synergistic effects were observed in combination with EGFR antibody cetuximab in colony formation assays with KRAS mutant cells. PK profiling revealed oral bioavailability of BH-501242 in multiple species and dose dependent plasma exposures in mouse xenograft tumor models. BH-501242 demonstrated excellent anti-tumor activity in multiple CDX mouse models with various KRAS mutations, including GP2D and HPAC models with G12D mutation, H441 with G12V, and MiaPaca-2 with G12C, etc. In conclusion, the strong preclinical profile provides a strong rationale for the advancement of BH-501242 into further development."

Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Title: Design and discovery of BH-501242, a novel pan-KRAS on/off inhibitor targeting KRAS switch II pocket (#5120) (GlobeNewswire) - "BlossomHill Therapeutics...announced it will introduce its next-generation KRAS pipeline at the American Association for Cancer Research (AACR) Annual Meeting 2026....Preclinical data demonstrate that BH-501242, a novel pan-KRAS inhibitor targeting the switch II pocket, potently inhibits a broad range of KRAS mutations, including G12D, G12V, and G12C, with sub-nanomolar cellular activity and robust tumor regression in multiple xenograft models."

Preclinical • Solid Tumor