GenFleet Therapeutics’ Blockbuster IPO Highlights China’s KRAS Innovation and G12D Ambitions
GenFleet Therapeutics raised HK$1.82B in its HKEX IPO, surging 106% on debut. With GFH925 approved for NSCLC and GFH375 showing strong early ORR in KRAS G12D NSCLC, the company is advancing its pipeline, partnerships, and competitive position in global oncology.
On September 19, 2025, GenFleet Therapeutics (02595.HK) debuted on the Hong Kong Stock Exchange, raising HK$1.82 billion and closing up 106% on its first day. The IPO underscores growing investor enthusiasm for China’s biotech innovators targeting historically “undruggable” oncogenes.
GenFleet’s lead asset, GFH925 (fulzerasib, Dubert®), is commercially approved in China for advanced NSCLC with KRAS G12C mutations, marking China’s first and the world’s third approved KRAS G12C inhibitor. The company has licensed commercialization rights to Innovent Biologics, meaning GenFleet’s revenue depends on its partner’s sales performance. Despite approval, the company remains unprofitable, reflecting early-stage commercialization of GFH925.
Pipeline Overview
GenFleet focuses primarily on KRAS-targeted oncology, with exploratory work in autoimmune and inflammatory diseases:
- GFH925 (fulzerasib, Dubert®) – KRAS G12C inhibitor, approved in China for NSCLC. Revenue is partner-dependent.
- GFH375 (VS-7375) – oral KRAS G12D ON/OFF inhibitor, developed in collaboration with Verastem Oncology. Verastem holds ex-China commercialization rights, while GenFleet retains Greater China markets.
- GFH312 – immuno-inflammatory program; development currently stalled.
The company’s near-term focus remains on GFH925 commercial traction and advancing GFH375 into later-stage clinical development.
KRAS Landscape: G12C vs. G12D
- KRAS G12C (~13% NSCLC) – successfully targeted by sotorasib (Lumakras) and adagrasib (KRAZATI), approved via accelerated approval based on ORR and DoR; no OS benefit required.
- KRAS G12D (~35–40% of KRAS mutations) – prevalent in pancreatic (37%), colorectal (12.5%), and NSCLC (5%) cancers. No FDA-approved therapies yet. This remains a major unmet need, driving global efforts in selective inhibitors.
- Pan-RAS inhibitors – target multiple KRAS isoforms but face toxicity/efficacy trade-offs.
The field emphasizes maximizing ORR and durability while maintaining manageable safety, particularly in heavily pretreated populations.
GFH375 (VS-7375) – GenFleet/Verastem Collaboration
At IASLC WCLC 2025, Verastem reported Phase 1/2 data for GFH375 in advanced KRAS G12D NSCLC:
| Parameter | Result |
|---|---|
| Patients (NSCLC) | 26 evaluable across all doses; 16 at RP2D (600 mg QD) |
| ORR | 57.7% (all doses); 68.8% at RP2D |
| DCR | 88.5% (all doses); 93.8% at RP2D |
| Safety (Grade ≥3 TRAEs / SAEs) | 27.5% / 7.7%; no deaths reported |
| Common TRAEs | Diarrhea, nausea, vomiting, anemia, neutropenia, AST/ALT increase |
The cohort was heavily pretreated: 64% had ≥2 prior lines, and 96% had prior PD-1/PD-L1 therapy. GFH375 is the first dual ON/OFF KRAS G12D inhibitor to show such high ORR in a Phase 1/2 NSCLC study.
Verastem exercised its option to license GFH375 in January 2025, gaining development/commercial rights outside Greater China, while GenFleet maintains rights in China, Hong Kong, Macau, and Taiwan.
Competitive Landscape of KRAS G12D Inhibitors
| Compound | Company | Target | Indication | Phase | ORR / Key Efficacy | Safety (Grade ≥3 TRAEs) | Sample Size | Notes |
|---|---|---|---|---|---|---|---|---|
| GFH375 (VS-7375) | GenFleet / Verastem | KRAS G12D | NSCLC 2L+ | Phase 1/2 | 57.7% (all doses), 68.8% RP2D | 27.5% / 7.7%; no deaths | 26 NSCLC patients; 16 at RP2D | First dual ON/OFF KRAS G12D inhibitor; Verastem has ex-China rights |
| RMC-9805 | Revolution Medicines | KRAS G12D | NSCLC / PDAC 2L+ | Phase 1/1b | NSCLC: 61% ORR (relapsed), PDAC: 30–35% ORR | 2–5% (at 1200 mg QD) | ~40 patients across indications | Molecular glue inhibitor (ON-state); encouraging early activity |
| MRTX1133 | Mirati Therapeutics | KRAS G12D | NSCLC / PDAC | Phase 1/2 | 30–40% early ORR | Acceptable | ~20–40 pts | Dual ON/OFF inhibitor; BMS discontinued follow-up in 2025 |
| LY3962673 | Eli Lilly | KRAS G12D | Solid tumors | Phase 1a/1b | Not yet reported | TBD | Phase 1a/1b | Monotherapy & combo trials ongoing |
| QTX3034 | QuantRx | KRAS G12D-preferring | Solid tumors | Phase 1 | Not yet reported | TBD | Phase 1 | Monotherapy + cetuximab combo |
| ASP5834 | Astellas | KRAS G12D degrader | Solid tumors | Phase 1 | Not yet reported | TBD | Phase 1 | Pan-KRAS degrader |
| AZD0240 | AstraZeneca | KRAS G12D | Solid tumors | Phase 1 | Not yet reported | TBD |
Key Points:
- GFH375 stands out with high ORR (57–68%) in heavily pretreated NSCLC at RP2D, with manageable safety.
- RMC-9805 (Revolution Medicines) is an early-stage competitor with lower preliminary ORR (30–35%).
- Other programs are mostly early-phase, highlighting GFH375’s potential first-in-class positioning.
- KRAS G12C inhibitors (sotorasib, adagrasib) do not target G12D, leaving a significant unmet need.
Commercial and Strategic Considerations
- GFH925 revenue is partner-dependent on Innovent Biologics’ sales in China.
- GFH375 positions GenFleet to expand into G12D-driven NSCLC and other solid tumors, with Verastem leading international development.
- IPO proceeds (~HK$1.82B) provide runway for pipeline expansion and potential earlier-stage oncology programs.
Outlook
GenFleet’s IPO demonstrates strong confidence in China’s KRAS-targeted innovation. Key near-term priorities:
- GFH925 Commercial Performance – market uptake in China will validate early investor enthusiasm.
- GFH375 Development – larger NSCLC cohorts, longer follow-up, and Phase 2/3 filings are critical for global regulatory submissions.
- Pipeline Prioritization – decisions on GFH312 and other exploratory programs could diversify the portfolio.
Competitive Landscape:
- Revolution Medicines, Mirati, and other emerging G12D programs underscore the need for differentiation through durable efficacy and manageable safety.
- GenFleet’s partnership with Verastem allows ex-China commercialization, reducing geographic risk and enhancing global reach.
Conclusion:
KRAS G12D remains one of oncology’s largest unmet needs. GenFleet’s IPO, early clinical success, and strategic partnerships position it at the forefront of this frontier. While Revolution Medicines and other competitors are progressing, GFH375’s dual ON/OFF inhibition, high early ORR, and manageable safety profile suggest it may define the next generation of KRAS-targeted therapies—pending confirmation in pivotal trials.
References:
- GenFleet Therapeutics IPO announcement, HKEX, Sept 2025
- Verastem Oncology press release, “GFH375 in Advanced NSCLC at WCLC 2025,” Aug 2025
- IASLC WCLC 2025 abstract database
- FDA approvals: sotorasib (Lumakras), adagrasib (KRAZATI)
Disclaimer: This article is for informational purposes only and does not constitute investment advice or a recommendation to buy or sell securities. Readers should conduct their own due diligence and consult professional financial or medical advisors before making any investment or clinical decisions. The information herein is based on publicly available sources as of the publication date and may change over time.