Verastem announces anti-tumor efficacy of GFH375 at scientific meeting

Verastem Oncology’s discovery and development partner GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, unveiled research findings of GFH375, an oral KRAS G12D inhibitor, at the 2024 American Association for Cancer Research Annual Meeting. GenFleet entered into a discovery and development collaboration with Verastem to advance three novel oncology discovery programs related to RAS pathway-driven cancers. The collaboration provides Verastem a milestone-based option to license up to three compounds outside of China while GenFleet would retain rights inside of mainland China, Hong Kong, Macau, and Taiwan. GFH375 potently and selectively inhibits phospho-ERK signaling and proliferation in KRAS G12D mutant tumor cells. GFH375 also accumulates in tumor tissue and elicits sustained inhibition of the protein following a single oral administration. GFH375 induces tumor regression in multiple KRAS G12D CDX tumor models via oral administration. It also demonstrates potent anti-tumor activity in an intracranial CDX tumor model. GFH375 also holds the potential for treating KRAS G12D mutant cancers with brain metastases. Preclinical research also demonstrated the combination of avutometinib and GFH375 confers enhanced anti-tumor efficacy relative to either agent alone, indicating potential for future clinical combination. Avutometinib in combination with defactinib is being developed by Verastem Oncology with clinical development across multiple indications and was granted breakthrough therapy designation for low-grade serous ovarian cancer. GenFleet entered into a discovery and development collaboration with Verastem Oncology in 2023 to advance three oncology programs, the first program selected is GFH375.