GenFleet Therapeutics, a commercial-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, announced that the preclinical results of three programs have been selected for poster presentation at the 2025 American Association for Cancer Research (AACR) Annual Meeting. The event will take place from Apr. 25th to 30th in Chicago, where the preclinical findings of GenFleet’s multiple large- and small-molecule therapies (GFH276, GFS202A, and GFH375/VS-7375) will be unveiled. With their diverse molecular modalities and broad-spectrum indications, the novel therapies exemplify the robustness and creativity embedded in GenFleet's pipeline composition.
Firmly grounded in the experience from developing fulzerasib, a marketed KRAS G12C inhibitor, GenFleet has expanded its RAS-targeted matrix and will post preclinical data of its novel RAS-inhibiting therapy: GFH276, a small-molecule Pan RAS (ON) inhibitor. Also at this event, GenFleet will release the updated preclinical results of two clinical-stage assets: GFS202A represents the world's first bispecific antibody therapy treating cachexia, and GFH375 is well-positioned at the forefront of oral KRAS G12D inhibitor development. The diversity underscores GenFleet' s expertise in RAS-targeted therapy development and its sustainable capabilities to explore market opportunities across varied disease areas.
GFH276: A molecular glue Pan RAS (ON) inhibitor with broad spectrum anti-tumor activities
Abstract No.: 389
Start & End time：Apr. 27, 2 am – 5pm
Session title: Degraders and glues 1
GFH276, an IND-enabling stage molecular glue Pan RAS (ON) inhibitor, is designed to target multiple RAS subtypes of GTP-bound state. In biochemical assays, GFH276 disrupted the binding of GMPPNP-bound KRAS G12C, G12D or G12V mutants or wild type KRAS, HRAS or NRAS proteins. Moreover, GFH276 showed no off-target activity in kinase selectivity and preclinical safety tests. Compared to SIIP-based KRAS G12C inhibitors, GFH276 was observed not susceptible to upstream RTK-reactivation by EGF stimulation and remained effective against cell lines carrying secondary KRAS mutations or RTK alterations, or with induced resistance to the first-generation KRAS inhibitors.
GFS202A, a novel GDF15×IL-6 bispecific antibody for the treatment of cachexia
Abstract No.: 6078
Start & End time：Apr. 29, 2am – 5pm
Session Title: Antibodies 3: multi-target checkpoint inhibitors and immune Activators
GFS202A has received IND approval in China for a phase I study treating cancer cachexia patients. As a complex metabolic syndrome, cachexia is highly prevalent in chronic conditions such as cancer, AIDS, heart failure, chronic obstructive pulmonary disease (COPD).
GFS202A exhibits high affinity to human GDF15 and IL-6. In preclinical research, GFS202A was observed to effectively reverse body weight loss and render dose-dependent increase in body weight, adipose tissue and muscle mass in animal models. Notably, GFS202A reduced animals’ C-reactive protein level more effectively than benchmark. Meanwhile, GFS202A demonstrated well tolerability in NHP toxicity study.
GFH375 (VS-7375): An oral, selective KRAS G12D (ON/OFF) inhibitor with potent anti-tumor efficacy as single agent and in combination with other anticancer therapies in preclinical models
Abstract No.: 4394
Start & End time：Apr. 29, 9am – 12pm
Session title: RAS inhibitors, experimental and molecular therapeutics
GFH375/VS-7375, a clinical-stage oral KRAS G12D inhibitor, exhibited potent selectivity in cell lines bearing G12D mutation and induced strong tumor regressions in multiple colorectal & pancreatic cancer models. Enhanced anti-tumor efficacy compared to GFH375 monotherapy was observed in preclinical combinations of GFH375 with cetuximab (anti-EGFR antibody) and avutometinib (RAF/MEK clamp) respectively. In the preclinical combo research of GFH375 with cetuximab, all mice were observed with complete response in a colorectal cancer model.
About GFH276, GFS202A and GFH375/VS-7375
GFH276 is a novel small-molecule panRAS (ON) inhibitor hijacking Cyp A to target active, GTP bound RAS proteins of most wild/mutant subtypes, including most commonly found KRAS mutant (G12C, G12D, G12V, etc.) proteins.
GFS202A, a GDF15/IL-6 bispecific cachexia therapy, has received IND approval for a phase I clinical trial treating cancer cachexia. The prevalence of cachexia exceeds 50% in certain cancer types and contributes to a mortality rate of up to 30%. Overexpression of GDF15 and IL-6, commonly observed in cachexia, is relevant to significant morbidity and mortality among cancer patients.
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.
About GenFleet Therapeutics
GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies, is dedicated to serving significant global unmet medical needs in oncology and immunology. Based on the deep understanding of disease biology and translational medicine, GenFleet’s proprietary and fully integrated R&D platform highlights 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 - both small molecules and biologics. Its pipeline includes over 10 programs, many of which have entered multi-regional clinical trials across China (including Taiwan), the United States, Europe and Australia. To date, GenFleet has over 5 clinical studies encompassing IND stage to phase II studies and completed co-development partnerships with numerous publicly listed companies worldwide.
GenFleet is expected to progress additional programs into the clinic, as well as transition from a clinical stage biotech company into a commercial stage biopharmaceutical company in the next 3-5 years.
