Portfolio News
GenFleet Therapeutics announced that preclinical data for GFH276, a molecular glue Pan RAS (ON) inhibitor, were presented in a poster session at the 2026 American Association for Cancer Research (AACR) Annual Meeting on April 21 (local time). 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. Furthermore, GFH276 exhibited robust anti-tumor synergy and extended tumor-free survival when combined with cetuximab, chemotherapy, or anti PD-1 monoclonal antibodies respectively in animal studies. As the world's third Pan RAS inhibitor entering clinical development, early clinical data of GFH276 correlates with its preclinical efficacy and safety profile.
“GenFleet ranks among the world’s leading developers of RAS-focused pipeline, with multiple candidates demonstrating industry leading pace in China or globally. Leveraging an extensive compound library targeting RAS-inhibiting therapeutics, we have established a suite of continuously upgraded R&D platforms to underpin our forward-looking program initiation. Through the development of small molecule therapies with diverse mechanisms of action, innovative ADCs, and highly differentiated pipeline, we are building a robust and synergistic portfolio, to address unmet clinical needs and deliver transformative treatments for patients with refractory malignancies.” stated Fusheng Zhou, Ph.D., Vice President of our GenFleet’s Drug Discovery Department.
Superior TGI achieved at 1/3 dosage of RMC‑6236 across multiple tumor models
In models of non‑small cell lung cancer (NSCLC), pancreatic cancer, and colorectal cancer (CRC) harboring diverse RAS mutations (including KRAS G12C, G12D, G12V, and G13D), oral administration of GFH276 at 3 mg/kg QD yielded comparable or superior TGI relative to RMC‑6236 dosed at 10 mg/kg QD over the same treatment period. In animal models, continuous once‑daily oral dosing of GFH276 at 0.3-1 mg/kg for two weeks demonstrated dose‑dependent anti‑tumor activity.
Broad potential of combination with standard‑of‑care therapies
In three‑week animal studies, low‑dose single‑agent GFH276 (0.3-1 mg/kg QD) achieved anti‑tumor activity comparable to single‑agent cetuximab or chemotherapy (gemcitabine plus paclitaxel). Combination of GFH276 with cetuximab (in CRC models) or chemotherapy (in pancreatic ductal adenocarcinoma models) produced marked synergistic activity, with anti‑tumor efficacy far exceeding that of either agent alone.
In the same three‑week studies, single‑agent GFH276 (0.3-3 mg/kg QD) outperformed anti‑PD‑1 antibody monotherapy. Combining GFH276 with anti‑PD‑1 antibody also yielded strong synergistic anti‑tumor effects and significantly improved tumor‑free survival for months following treatment cessation, with synergistic activity increasing in a dose‑dependent manner.
Activity against diverse RAS mutations and KRAS G12Ci‑resistant cell lines
Via a novel CypA‑GFH276‑RAS complex mechanism, GFH276 inhibits most activated wild‑type and mutant RAS isoforms. It demonstrated growth inhibition in multiple KRAS G12C inhibitor‑resistant cell lines and potent activity across a broad range of RAS‑dependent cancer cell lines, including those harboring RAS alterations, such as RTK alterations (upstream of RAS), and BRAF mutations (downstream of RAS).
In prior kinase selectivity and safety‑related profiling, GFH276 showed no off‑target activity, supporting its favorable safety and target specificity.
About RAS and GFH276
GFH276 is an oral novel small-molecule Pan RAS (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. Preclinical research of GFH276 demonstrates dose-dependent anti-tumor activity and drives tumor regression in multiple KRAS mutant tumor models. GFH276 also holds the potential to outperform the mainstream SIIP (switch II pocket)-based KRAS inhibitors in overcoming adaptive and acquired resistance.
