Pipeline | Verastem, Inc.

At Verastem, we are pursuing unexplored avenues in the RAS/MAPK pathway with 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. We are exploring both monotherapy and synergistic combinations with our current
pipeline and external assets. Our pipeline includes:

Avutometinib, an oral RAF/MEK clamp: we are evaluating avutometinib in multiple combination studies in low-grade serous ovarian cancer, pancreatic cancer, non-small cell lung cancer and other RAS/MAPK-driven tumors.
Defactinib, an oral FAK inhibitor: we are evaluating defactinib in combination with avutometinib and other external assets in low-grade serous ovarian cancer, pancreatic cancer, non-small cell lung cancer and other RAS/MAPK-driven tumors.
VS-7375, an oral KRAS G12D (ON/OFF) inhibitor: we are evaluating VS-7375 as monotherapy and in combination, in patients with advanced KRAS G12D-mutated solid tumors, including pancreatic cancer, non-small cell lung cancer, and colorectal cancer.
2 undisclosed RAS Pathway-related targets: from our partnership with GenFleet Therapeutics including pancreatic cancer, non-small cell lung cancer, colorectal cancer, and other advanced solid tumors.

Verastem-Sponsored Trials

Indication	Study Name	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
R/R LGSOC Regimen: avutometinib + defactinib vs investigator’s choice of treatments (ICT) Study Name: RAMP 301	RAMP 301	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
KRAS G12D-mutant Solid Tumors Regimen: VS-7375 as monotherapy and in combination Study Name: VS-7375-101	VS-7375-101	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
Pancreatic Ductal Adenocarcinoma Regimen: avutometinib + gemcitabine/nab-paclitaxel + defactinib Study Name: RAMP 205	RAMP 205	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
R/R NSCLC (KRAS G12C) Regimen: avutometinib + sotorasib +/- defactinib Study Name: RAMP 203	RAMP 203	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
R/R LGSOC^1,2 Regimen: avutometinib +/- defactinib Study Name: RAMP 201	RAMP 201	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved

¹FDA Breakthrough Therapy Designation
²Registration-directed trial

Verastem Collaboration with GenFleet Therapeutics

Verastem Oncology entered into a collaboration agreement with GenFleet Therapeutics that includes three discovery programs and provides Verastem with exclusive options to license three compounds selected for collaboration after successful completion of pre-determined milestones in Phase 1 trials. The licenses would give Verastem Oncology development and commercialization rights outside of the GenFleet territories of mainland China, Hong Kong, Macau, and Taiwan.

Verastem has identified GFH375/VS-7375, a potential best-in-class, potent and selective oral KRAS G12D (ON/OFF) inhibitor, as the lead discovery program from the collaboration. GenFleet’s IND for GFH375/VS-7375 was approved in China in June 2024 and the Phase 1/2 trial in KRAS G12D-mutant solid tumors was subsequently initiated and the first patient was dosed in July 2024.

Indication	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
KRAS G12D-mutant Solid Tumors Regimen: Oral KRAS G12D (ON/OFF) Inhibitor GenFleet initiated Phase 1/2 trial in China.	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
Undisclosed	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
Undisclosed	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved

Investigator-Sponsored Trials +

We believe in the power of collaboration to help us push forward with new and promising cancer treatments. Our Verastem Oncology Investigator Sponsored Trial (IST) program strives to advance medical and scientific knowledge for our product candidates and disease states of interest. We welcome partnerships with researchers and sponsoring institutions that build on this mission.

Indication	Study Name	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
R/R LGSOC Regimen: avutometinib + defactinib Study Name: IST-FRAME	IST-FRAME	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
Gynecological Cancers (RAS Pathway-driven) Regimen: avutometinib + defactinib Study Name: IST	IST	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
Mesonephric Regimen: avutometinib + defactinib Study Name: IST	IST	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
R/R NSCLC (KRAS mt) Regimen: avutometinib + everolimus (mTORi) Study Name: IST	IST	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
R/R Colorectal Cancer Regimen: avutometinib + cetuximab (EGFRi) Study Name: IST	IST	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
ER+ Breast Cancer Regimen: avutometinib + abemaciclib + fulvestrant Study Name: IST	IST	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
Mesonephric Gynecologic Cancers Regimen: avutometinib + defactinib Study Name: IST	IST	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved

These studies are investigating treatments or outcomes that have not received approval from a health authority. We are working diligently to demonstrate the safety and efficacy of these products, but there is no guarantee that the outcome of these studies will result in approval. We invite you to review our expanded access policy.

Investigator Sponsored Trial Form

For additional details regarding our IST program or to submit a research request, please download, complete and submit the form below via email to verastem-IST@verastem.com.

Download Form

Research Collaborations

Verastem Oncology also accepts proposals for preclinical research collaborations. For more information, please reach out to us at research@verastem.com.