GenFleet Therapeutics announced preclinical data for GFS784, an innovative antibody–drug conjugate (ADC), were featured in a poster presentation at the 2026 American Association for Cancer Research (AACR) Annual Meeting on April 21 (local time). GFS784 is generated from the FAScon™, GenFleet’s globally innovative ADC platform on conjugation engineering to combine functional antibodies with synergistic targeted payloads. GFS784 links a molecular glue Pan RAS (ON) inhibitor to cetuximab. Preclinical studies showed potent activity in RAS mutant models, both DXd sensitive and DXd resistant models, as well as anti tumor efficacy in EGFR mutant and TKI resistant models, supporting its potential as a monotherapy to deliver superior benefit compared with double-agent combination regimens.
GFS784, a next-generation ADC with a novel Pan RAS (ON) inhibitor payload (Poster No.: 4536)
GFS784 monotherapy showed comparable anti-tumor efficacy and superior safety versus RMC-6236 plus anti-EGFR antibody combination
In three week animal studies, low dose of GFS784 (5–10 mg/kg, Q3W) achieved anti tumor efficacy comparable to the combination of low dose RMC-6236 (10 mg/kg, QD) plus cetuximab. A weekly administration of GFS784 (5 mg/kg, QW) elicited even more pronounced activity, matching the anti-tumor effect combining high dose RMC-6236 (25 mg/kg, QD) plus cetuximab.
Across all dose levels tested over three weeks, GFS784 maintained stable body weight in animals with no substantial weight loss, and the relative change in body weight (RCBW) was significantly superior to the RMC- 6236 plus cetuximab combination regimen.
Broad patient potential: common activity preserved in RAS-mutant, EGFR-mutant, TKI-resistant and DXd insensitive models
The payload of GFS784 is a molecular glue Pan RAS (ON) inhibitor that acts via a CypA-GF005095-RAS complex, inhibiting most activated wild type and mutant RAS isoforms. While the single agent of cetuximab targets a broad patient population with EGFR alterations, the dual RAS/EGFR inhibition delivers pathway synergy potentially covering 50-90% of patients with non small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC).
In EGFR-mutant NSCLC animal models, single dose administration of GFS784 over three weeks exerted consistent, dose dependent anti tumor activity in multiple osimertinib-sensitive and -resistant models, including models harboring concurrent TKI resistance and cMET amplification. GFS784 also demonstrated dose dependent anti-tumor activity, even in DXd insensitive tumor models in a three week experiment.
FAScon™: functional antibodies and synergistic targeted payloads to transform ADC therapeutic index and reduce adaptive resistance
The FAScon™ platform is engineered to pioneer the next generation of ADCs by evolving carrier antibodies into functional antibodies and replacing cytotoxic payloads with synergistic targeted payloads. The platform strategically integrates large- and small-molecule inhibitors that modulate complementary signaling pathways, an approach poised to boost therapeutic efficacy, overcome potential resistance, and inspire next-generaiton ADC development.
GFS784, derived from the FAScon™ platform, is the world’s first ADC employing a molecular glue Pan RAS inhibitor as its targeted payload. Beyond its therapeutic potential, preclinical data highlighted favorable safety properties of GFS784, demonstrating a prolonged half-life in tumor tissue and a short half-life in circular system. Coupled with potent bystander effect, this safety profile enhanced therapeutic efficacy while lowering off-target risks. The unique delivery of targeted payload would further circumvent potential toxicities, which are usually observed with oral RAS inhibitors.
About FAScon™ and GFS784
FAScon™ is a globally innovative ADC platform that combines functional antibodies with mechanistically synergistic targeted payload, upgrading traditional carrier antibodies into functional antibodies to link with targeted payloads instead of cytotoxic payloads. It aims to transform next generation ADC development with improved efficacy, wider therapeutic index, and the ability to overcome resistance. Starting with mechanistically synergistic ADCs targeting the RAS pathway, the platform will expand into other signaling pathways and disease areas beyond oncology.
GFS784 utilizes a synergistic RAS+EGFR dual target mechanism, pairing a molecular glue Pan RAS (ON) inhibitor payload with cetuximab (anti EGFR antibody). It potently inhibits RAS mutant, EGFR mutant, and TKI resistant tumors, and suppresses tumor growth in both DXd sensitive and DXd insensitive ADC models. Additionally, GFS784 shows excellent cell membrane permeability to support robust bystander killing, and maintains high potency in cytotoxic resistant cell lines at picomolar concentrations. It also demonstrates favorable safety characteristics in preclinical evaluations.
About GenFleet Therapeutics
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 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.
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