Verastem Oncology Exercises Option Early to License VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, from GenFleet Therapeutics and Provides Preliminary Clinical Update on Phase 1 Study in China

VS-7375 is a potential best-in-class oral and selective KRAS G12D (ON/OFF) inhibitor currently in Phase 1 development in China in advanced KRAS G12D mutant solid tumors; Verastem anticipates filing a U.S. IND application for VS-7375 during Q1 2025 and expects to initiate a Phase 1/2a study mid-2025

License establishes global development and commercialization rights for Verastem for VS-7375 outside of China, Hong Kong, Macau, and Taiwan

VS-7375 demonstrated oral bioavailability, no dose-limiting toxicities across six dose levels, and partial responses, including patients with pancreatic and lung cancers in preliminary clinical data from the Phase 1 dose-escalation study in China

BOSTON--(BUSINESS WIRE)--Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, today announced it has exercised early the option to license from GenFleet Therapeutics VS-7375 (also known as GFH375), a potential best-in-class oral and selective KRAS G12D (ON/OFF) inhibitor. In addition, the Company announced preliminary clinical data from the Phase 1 study being conducted by GenFleet in China.

As previously announced by GenFleet, 26 patients have been treated with VS-7375 in a Phase 1 dose-escalation study being conducted in China. Both confirmed and unconfirmed partial responses have been observed, including patients with metastatic pancreatic cancer and advanced non-small cell lung cancer. In addition, six dose cohorts have been cleared with no dose-limiting toxicities (DLTs) observed. In the study, oral dosing of VS-7375 has achieved plasma levels in patients that correlate with efficacious exposures that induced deep tumor regressions across all preclinical KRAS G12D tumor models as presented in collaboration with GenFleet at the AACR 2024 annual meeting.

Enrollment in the Phase 1 dose-escalation study in China is ongoing. Verastem remains on track to file a U.S. investigational new drug (IND) application for VS-7375 during the first quarter of 2025 and expects to initiate a Phase 1/2a study in mid-2025. The Companies expect to share updated preclinical and clinical data at upcoming medical meetings in mid-2025.

“Bringing VS-7375 formally into our pipeline allows us to leverage our scientific and development expertise in the RAS/MAPK-pathway to target KRAS G12D - the most prevalent KRAS mutation in human cancers,” said Dan Paterson, chief executive officer at Verastem Oncology. “Our decision to exercise the option early for VS-7375 was based on the safety, pharmacokinetics and efficacy data to date in the Phase 1 study in China, which are in line with our expectations and, importantly, indicate that patients are generally achieving oral bioavailability with exposures that correlate with strong tumor regressions across KRAS G12D mutant preclinical models. We look forward to building on the work GenFleet has started in China to bring VS-7375 to the clinic in the U.S. in mid-2025.”

In August of 2023, Verastem entered into a discovery and collaboration agreement with GenFleet to advance three oncology discovery programs targeting RAS pathway-driven cancers. The collaboration was designed with a risk-sharing structure and flexibility for Verastem to exclusively license up to three compounds selected for collaboration after the successful completion of pre-determined milestones in Phase 1 trials. Under the terms of the license for VS-7375, Verastem receives an exclusive global license to VS-7375 outside of the GenFleet markets of mainland China, Hong Kong, Macau, and Taiwan.

About VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor

VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. VS-7375 is the lead program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. GenFleet’s IND for VS-7375 (known as GFH375 in China) was approved in China in June 2024, and the first patient was dosed in a Phase 1/2 study in July 2024.

The Phase 1 portion of the study is being conducted in approximately 20 hospitals in China and will evaluate the safety and efficacy of VS-7375 in patients with advanced KRAS G12D mutant solid tumors. The Phase 1 study will determine the recommended Phase 2 dose (RP2D) and the Phase 2 will further evaluate the efficacy and safety of VS-7375 in patients with advanced solid tumors, such as pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer.

Preclinical data presented at the American Association for Cancer Research (AACR) Annual Meeting in April 2024 demonstrated oral bioavailability across preclinical species, strong anti-tumor activity as a single agent, and potent efficacy in an intracranial tumor model suggesting the potential to treat brain metastases.

KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers. The KRAS G12D mutation occurs most commonly in pancreatic (37%), colorectal (12.5%), endometrial (8%) and non-small cell lung (5%) cancers. Currently, no therapies are approved by the U.S. Food and Drug Administration targeting KRAS G12D.

About the GenFleet Therapeutics Collaboration

The collaboration with GenFleet Therapeutics aims to advance three oncology discovery programs related to RAS/MAPK pathway-driven cancers. The collaboration provides Verastem with an exclusive option to obtain a license for each of the three compounds in the collaboration after the successful completion of pre-determined milestones in a Phase 1 trial. Verastem selected VS-7375 (also known as GFH375), an oral KRAS G12D (ON/OFF) inhibitor, as its lead program in December 2023 and the license for VS-7375 that was exercised in January 2025 is the first one from this collaboration. The licenses would give Verastem development and commercialization rights outside of the GenFleet markets of mainland China, Hong Kong, Macau, and Taiwan.

About Verastem Oncology

Verastem Oncology (Nasdaq: VSTM) is a late-stage development biopharmaceutical company committed to the development and commercialization of new medicines to improve the lives of patients diagnosed with RAS/MAPK pathway-driven cancers. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition, FAK inhibition and KRAS G12D inhibition. For more information, please visit www.verastem.com and follow us on LinkedIn.

Contacts

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