The studies highlighted the potent and differentiated profile of GFH375, an oral KRAS G12D (ON/OFF) inhibitor, demonstrating superior anti-tumor activity, enhanced potency and selectivity, and more durable pathway suppression compared with other KRAS/RAS inhibitors across animal models and cellular assays.
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.
Preclinical research showed at one-third the dosage of RMC 6236, GFH276 exerted comparable or enhanced tumor growth inhibition (TGI) in multiple RAS-mutant tumor models.
As an allosteric activator of the KEAP1-CUL3 complex, GFH603 enhances the formation of KEAP1-CUL3 E3 ligase complex and thereby promotes NRF2 degradation. KEAP1 is a prevalent co-mutated gene in RAS-mutant tumors, and preclinical research demonstrated that GFH603 exerted potent antitumor efficacy both as a single agent and in combination with a Pan RAS inhibitor.
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.
As to global development, GenFleet initiated a European multi-center KROCUS study led by lung cancer expert Dr. Rafael Rosell in March 2023. As of the data cutoff date, the regimen achieved an objective response rate (ORR) of 80%, disease control rate (DCR) of 100%, and median progression-free survival (PFS) of 12.5 months among evaluable patients. The regimen also delivered notable activity in patients with brain metastases, maintained high dose intensity of both agents throughout treatment, an
GenFleet’s RAS-targeted matrix encompasses multiple selective and Pan RAS inhibitors, as well as targeted therapies for potential co-mutations associated with the RAS pathway. This matrix includes small and large molecules with diversified modalities and mechanisms; preclinical research data of three compounds - GFH276 (non-degrading molecular glue), GFS784 (novel ADC linking functional antibody with synergistic targeted payload) and GFH603 (molecular glue-like covalent allosteric activator) - w
The Company will also be included as a constituent of Hang Seng Index Series starting today, including the Hang Seng Composite Index (HSCI), Hang Seng Stock Connect Hong Kong Index, and Hang Seng Innovative Drug Index, according to the quarterly review results published by Hang Seng Indexes Company Limited in Feb. 2026.
