GENFLEET-B (02595.HK): First Clinical Data for Pan-RAS Inhibitor GFH276 Selected as ESMO LBA

NewTimeSpace News: On 26 October 2026, GenFleet Therapeutics (Shanghai) Inc. (stock code: 2595) announced that preliminary data from a study of GFH276, an oral molecular glue pan-RAS inhibitor, in pretreated RAS-mutant solid tumours were presented as a late-breaking abstract (LBA) and on-site oral presentation at the 2026 ESMO Congress on 25 October local time, presented by Dr Ma Yuxiang (马宇翔) of Sun Yat-sen University Cancer Center.

The Phase Ia dose-escalation study (NCT07198321) covers a broad range of RAS mutation subtypes, mainly pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC) and colorectal cancer, at doses of 5 to 320 mg once daily. As at 15 September 2026, 61 evaluable PDAC patients (40-160 mg) had an overall objective response rate (ORR) of 41.1% and a disease control rate (DCR) of 91.8%, with an ORR of 43.1% in those without prior RAS-targeted therapy; 11 evaluable NSCLC patients (80-160 mg) had an ORR of 45.5% and a DCR of 72.7%, with an ORR of 55.6% in those without prior RAS-targeted therapy.

On safety, as at 15 July 2026, among 80 patients treated at 40-160 mg, most treatment-related adverse events (TRAEs) were grade 1-2, commonly rash-type events, anaemia, oral mucositis and diarrhoea; grade 3 events were mainly rash-type (7.5%), with all other grade 3 events below 4% each and no grade 4-5 events. Partial responses were observed from 40 mg once daily, and no dose-limiting toxicities were seen at 40-160 mg without prophylactic medication.

GFH276 uses a triple-complex (CypA-GFH276-RAS) mechanism that inhibits most activated wild-type and mutant RAS subtypes, including KRAS G12C, G12D and G12V as well as NRAS and HRAS; compared with switch II pocket KRAS inhibitors, it may overcome adaptive and acquired resistance. The Company said the data support mid- to late-stage studies as a monotherapy and in combinations with EGFR antibodies or chemotherapy.