GenFleet Therapeutics (2595.HK): Encouraging clinical debut of GFH276 supports further exploration as pan-RAS backbone

GFH276 (oral pan-RAS(ON) molecular glue) had its clinical debut at ESMO (LBA33) as monotherapy in previously treated RAS-mutant solid tumors. The data showed a 41% ORR in 2L+ PDAC (N=61, 40-160mg, 73% at 3L+), above our preview of 30%/20% bar for 2L/3L+ monotherapy. Safety appeared manageable without prophylactic treatments, with key AE of interest (G3+ rash/stomatitis of 2%/0) well-managed. We view the update as positive for GFH276 as the potential pan-RAS backbone for GenFleet. In the ph1 dose escalation, PDAC patients treated at 40-160mg achieved ORR of 41% (43% in RAS-naive patients) and DCR of 92%, in a heavily pretreated population (c.73% had 2+ prior lines, 78% liver metastases). In NSCLC (80-160mg, N=11), ORR was 46% with DCR of 73%, with the caveat of small sample size. At 40-160mg without prophylactic medications (N=80), there were no DLTs, no G4/5 TRAEs, G3 TRAE of 27.5%, and only 1.3% discontinuation. With DLTs mainly rash observed at 200mg or above, toxicity appeared more