Verastem (VSTM) H.C. Wainwright 28th Annual Global Investment Conference summary

Pipeline and strategy overview

• Two main platforms: a commercial-stage avutametnib plus defactinib combination (CO-PACK) for KRAS-mutated low-grade serous ovarian cancer, and the VS-7375 KRAS G12D inhibitor program advancing in multiple tumor types.

• VS-7375 is in phase II trials for pancreatic, lung, and colorectal cancers, with phase III trials planned to open by the first half of 2027.

• Commercial efforts focus on expanding prescriber depth, especially in community settings, and optimizing patient starts and therapy duration.

• Confirmatory phase III RAMP 301 study is fully enrolled, with data expected next year to support broader use in both KRAS-mutated and wild-type populations.

• Upcoming data presentations at major conferences will compare CO-PACK efficacy to standard of care and provide external control analyses.

Clinical development and differentiation

• RAMP 205 trial in frontline metastatic pancreatic cancer showed a 52% response rate and about one year overall survival with avutametnib, defactinib, and chemotherapy.

• VS-7375 is a dual on/off KRAS G12D inhibitor with high potency, selectivity, and favorable safety profile, avoiding common toxicities of pan-RAS inhibitors.

• Dose-dependent exposure allows for higher, well-tolerated dosing, providing flexibility for combinations and addressing drug-drug interactions.

• Mechanistic rationale and preclinical data support combining VS-7375 with EGFR inhibitors in both pancreatic and colorectal cancers.

• October data will include intent-to-treat analyses for pancreatic, lung, and colorectal cohorts, focusing on best-in-class efficacy and combination strategies.

Market opportunities and future directions

• Pancreatic cancer is seen as a proving ground for VS-7375, with 40% of patients harboring G12D mutations and a need for safer, more effective targeted therapies.

• Colorectal cancer represents a significant unmet need, with plans to demonstrate efficacy in combination with anti-EGFR agents.

• Lung cancer studies include a cohort targeting brain metastases, aiming to establish VS-7375 as the preferred option for G12D-driven disease.

• Three phase III frontline studies are planned for the first half of next year, aiming for comprehensive confirmatory data across major tumor types.

• Future directions include exploring combinations with FAK inhibitors, pan-RAS, and PRMT5 inhibitors to extend survival and benefit in RAS-driven cancers.