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GenFleet Therapeutics (2595.HK) announced that oral KRAS G12D (ON/OFF) inhibitor GFH375 has been granted with the Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation of China’s National Medical Products Administration. The designation is intended for GFH375 monotherapy treating patients with KRAS G12D-mutant metastatic pancreatic cancer who have received at least one prior systemic therapy, representing China’s first BTD inclusion of KRAS G12D inhibitor monotherapy for pancreatic cancer. Earlier this year, GFH375 became the first KRAS G12D inhibitor granted with China’s BTD for non-small cell lung cancer. GenFleet’s partner Verastem Oncology started overseas development of GFH375 (known as VS-7375 outside of China) last year, and VS-7375 was granted with US FDA’s Fast Track Designation for the treatment of KRAS G12D-mutant pancreatic ductal adenocarcinoma across all lines of therapy.
GFH375 entered the world’s first phase III registrational study of a KRAS G12D inhibitor monotherapy (GFH375X1301) in 2025. This is also the world's first registrational study of an oral KRAS G12D inhibitor, being conducted in approximately 40 clinical sites in China. GFH375 received clinical trial approval in China for a phase I/II trial in June 2024; the monotherapy data from treating solid tumors, pancreatic ductal adenocarcinoma and non-small cell lung cancer were selected as late-breaking abstracts and oral presentations at the ASCO, WCLC and ESMO annul meetings consecutively in 2025. Multiple monotherapy and combination trials of GFH375/VS-7375 are currently underway in all lines of setting in China (by GenFleet) and globally (by Verastem).
Yu Wang, M.D., Ph.D.
Chief Medical Officer of GenFleet
“We are delighted that the product has received multiple regulatory designations globally, vindicating the promising efficacy of GFH375 in various cancer types. In the clinical development of GFH375, we are deeply impressed with the urgent need for innovative targeted therapies among patients with pancreatic cancer and KRAS G12D mutations. GenFleet looks forward to the continued progress of GFH375’s clinical programs to bring new treatment options. We expect to disclose updated data from GFH375 trials across various indications at academic conferences this year.”
Pancreatic cancer is among the most aggressive malignancies due to its rapid progression, high tumor heterogeneity and complex tumor microenvironment, with a 5-year survival rate below 10%. RAS mutations occur in up to 90% of pancreatic cancer cases (with a KRAS G12D mutation ratio of approximately 40%). Patients with KRAS G12D mutations have significantly shorter overall survival and relapse-free survival compared to those with wild-type KRAS or other KRAS mutant subtypes. GenFleet’s pipeline features top-tier selective and Pan RAS inhibitors, together with a bispecific antibody for cancer cachexia, which are poised to establish a novel targeted matrix for pancreatic cancer. The Company’s collaborative project, “Research on the Pathogenesis of Pancreatic Cancer and a New Paradigm for Precise Clinical Diagnosis and Treatment”, was successfully awarded a National Science and Technology Major Project in 2025.
GFH375 is an orally active, potent, highly selective small-molecule KRAS G12D (ON/OFF) inhibitor designed to target the GTP/GDP exchange, thereby disrupting the activation of downstream pathways and effectively inhibiting tumor cell proliferation. Preclinical studies demonstrated dose-dependent inhibition in models bearing KRAS G12D mutation; GFH375 also demonstrated low off-target risk in kinase selectivity and safety target assays.
GenFleet entered into a discovery and development collaboration with Verastem Oncology (Nasdaq: VSTM) to advance three novel oncology discovery programs related to RAS/MAPK pathway-driven cancers. The collaboration provides Verastem with an exclusive option to obtain a license for each of the three compounds in the collaboration after the successful completion of pre-determined milestones in a Phase I trial. Verastem selected GFH375/VS-7375, an oral KRAS G12D (ON/OFF) inhibitor, as its lead program from the collaboration, in December 2023 and the license for GFH375 that was exercised in January 2025 is the first one from this collaboration. The licenses would give Verastem development and commercialization rights outside of China while GenFleet would retain rights inside of China.
With a focus on cutting-edge therapies, GenFleet Therapeutics is dedicated to serving significant unmet medical needs globally in oncology and immunology. Leveraging its deep understanding of disease biology and translational medicine, GenFleet has established a proprietary and fully integrated R&D system that yields a robust pipeline of multiple cutting-edge products with novel mechanisms and global IP.
Since its inception in 2017, GenFleet has built up industry-leading capabilities and expertise in developing novel drug candidates spanning small molecules and biologics. Its pipeline comprises numerous programs that have advanced to later-stage or pivotal clinical trials across China, the United States and Europe.
The company has set up a highly differentiated RAS-targeted matrix including selective and pan-RAS inhibitors of diverse molecular types, with most assets leading their categories in clinical progress in China or globally. In addition, the company has pioneered a series of first-in-class combination therapies based on dual-target synergistic mechanisms. By integrating clinical needs and insights, GenFleet is dedicated to expanding its portfolio into major therapeutic areas including pancreatic cancer, NSCLC, and cachexia. Furthermore, it's strengthening its commercial collaborative network through strategic out-licensing agreements or clinical cooperations with prestigious listed companies across the world.
