Material Event Form 8 K

Item 8.01 Other Events.

Initiation of Rolling NDA and Interim Duration of Therapy Data

As previously disclosed, in May 2024, Verastem, Inc. (the "Company" or "Verastem") initiated the rolling submission of a New Drug Application ("NDA") to the U.S. Food and Drug Administration ("FDA") seeking accelerated approval of the combination of avutometinib and defactinib for patients with recurrent Kirsten rat sarcoma viral oncogene homolog ("KRAS") mutant ("KRAS mt") low-grade serous ovarian cancer ("LGSOC") who received at least one prior systemic therapy. The rolling review process allows Verastem to submit completed sections of an application for review by the FDA before all sections become available. The initial sections of the application will include the completed nonclinical and quality sections. The Company plans to seek the broadest label possible with mature RAMP 201 data to inform final indication. Previously, the FDA granted Orphan Drug Designation for the combination in LGSOC and Breakthrough Therapy Designation for the combination for treatment of patients with LGSOC with recurrent disease after one or more prior lines of therapy, including platinum-based chemotherapy. The Company plans to request a priority review of the NDA. Currently, there are no FDA-approved treatments specifically for recurrent LGSOC.

The Company estimates the total annual incident addressable market opportunity for this product candidate to be approximately $300 million for KRAS mt and approximately $270 million KRAS wild-type ("KRAS wt") populations, respectively. The Company estimates the total prevalent addressable market opportunity to be approximately $1.7 billion for KRAS mt and approximately $1.1 billion for KRAS wt populations, respectively. The Company's estimates of the patient population, pricing and revenue opportunities for its product candidates, including for KRAS mt and KRAS wt patients with LGSOC, are based on a number of internal and third-party estimates and assumptions, including, without limitation, internal forecasts, the median duration of treatment from initial interim clinical data and the assumed prices at which we can commercialize our product candidates. Specifically, the Company's estimates of total addressable market opportunities are based on: (a) estimated annual incidence of KRAS mt and KRAS wt populations of approximately 500 and 1,000 patients, respectively, (b) estimated prevalence of KRAS mt and KRAS wt populations of approximately 2,800 and 4,200 patients, respectively, (c) the average duration of therapy as observed in Verastem clinical trials of 18 months and eight months for KRAS mt and KRAS wt populations, respectively, and (d) an estimated cost of therapy of $34,000 per month consistent with other recent oncology drug launches.

The average duration of therapy included in this calculation is based, in part, on the estimated duration of therapy for patients dosed with the combination of avutometinib and defactinib for the combined Parts A, B, and C in RAMP 201 as of the latest data cutoff in February 2024. Amongst 115 patients, 58 enrolled with KRAS mutated LGSOC and 57 had wild-type, or non-mutated, KRAS. The estimated median duration of therapy for all patients is nine months and the estimated mean duration of therapy is 14 months. For KRAS mt, the estimated median duration of therapy is 14 months and the estimated mean duration of therapy is 18 months with 31 patients still on treatment as of the data cutoff date. For KRAS wt, the estimated median duration of therapy is seven months and the estimated mean duration of therapy is 11 months with 12 patients still on treatment as of the data cutoff date.

Estimated median duration of therapy was calculated using Kaplan-Meier methods. Estimated mean duration of therapy was calculated by projecting complete time on treatment for patients still on treatment by sampling from an exponential distribution conditional on the observed duration through the cutoff date.

GenFleet Collaboration

In August 2023, the Company entered into a collaboration and option agreement (the "GenFleet Agreement") with GenFleet Therapeutics (Shanghai), Inc. ("GenFleet") pursuant to which GenFleet granted the Company options to obtain exclusive development and commercialization rights worldwide outside of mainland China, Hong Kong, Macau, and Taiwan (the "GenFleet Territory") for up to three oncology programs targeting RAS pathway driven cancers (the "GenFleet Options"). The Company may exercise its GenFleet Options on a program-by-program basis. An investigational new drug application by GenFleet in China for GFH375/VS-7375, an oral KRAS G12D (ON/OFF) inhibitor, was cleared in June 2024, following which GenFleet initiated Phase 1/2 trial in solid tumors with KRAS G12D mutation for GFH375/VS-7375 in China in June 2024. In July 2024, the Company announced that the first patient had been dosed in a Phase 1/2 trial in China, conducted by GenFleet, evaluating GFH375/VS-7375, a KRAS G12D (ON/OFF) inhibitor. The Phase 1 study is being conducted in approximately 20 hospitals in China and will evaluate the safety and efficacy of GFH375/VS-7375 in patients with advanced KRAS G12D mutant solid tumors. The Phase 1 study will determine the recommended Phase 2 dose (RP2D) and then further evaluate in Phase 2 the efficacy and safety of GFH375/VS-7375 in patients with advanced solid tumors, such as pancreatic ductal adenocarcinoma, colorectal cancer and non-small cell lung cancer.