Verastem (VSTM) R&D Day 2025 summary

Portfolio and Strategic Focus

• Emphasis on RAS/MAPK-driven cancers with a portfolio including avutometinib (RAF/MEK inhibitor), defactinib (FAK inhibitor), and KRAS G12D inhibitor VS-7375, plus two undisclosed GenFleet collaboration targets.

• AVMAPKI FAKZYNJA co-pack (avutometinib + defactinib) received FDA approval in May 2025 for KRAS-mutated recurrent low-grade serous ovarian cancer, showing a 44% response rate and dual pathway inhibition.

• Pipeline includes ongoing collaborations, notably with GenFleet Therapeutics for VS-7375 development.

RAMP 205 Pancreatic Cancer Data Update

• RAMP 205 Phase 1/2 trial in newly diagnosed metastatic PDAC showed an 83% objective response rate and 92% disease control rate at dose level 1, with tumor shrinkage in all patients and manageable toxicity.

• Most patients in dose level 1 are exceeding historical median progression-free survival benchmarks for standard chemotherapy, with improved outcomes and tolerable side effects.

• Safety profile is manageable, with most adverse events being grade 1 or 2 and consistent with known profiles of component drugs.

• Expansion to 29 patients is underway, with a randomized pivotal Phase 3 study in 1L PDAC planned for 2026.

Mechanistic Insights and Preclinical Findings

• Avutometinib inhibits MEK and blocks compensatory RAF reactivation, while defactinib targets FAK-mediated resistance, together providing more complete RAS/MAPK pathway blockade.

• The combination with chemotherapy induces tumor regression and reduces liver metastases in KRAS/p53 pancreatic cancer models, with defactinib reducing stromal density.