Verastem Initiates COMMAND: A Registration-Directed Trial of Defactinib in Patients with Mesotheliom

Verastem Initiates COMMAND: A Registration-Directed Trial of Defactinib in Patients with Mesothelioma

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Verastem, Inc. (NAS: VSTM) , focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, today announced the initiation of COMMAND (Control Of Mesothelioma with MAiNtenance Defactinib). COMMAND is a registration-directed trial of lead cancer stem cell inhibitor defactinib (VS-6063) in patients with malignant pleural mesothelioma, a highly aggressive form of lung cancer with a high percentage of cancer stem cells.

COMMAND is a registration-directed, double-blind, placebo-controlled trial with Progression Free Survival (PFS) and Overall Survival (OS) as the primary endpoints. The study incorporates the opportunity to enrich for patients with tumors low in the biomarker, merlin. Preclinical and early clinical research has demonstrated that low merlin levels are predictive of increased effectiveness of FAK inhibitors such as defactinib. The COMMAND study will stratify patients to evaluate the effect of defactinib in both the overall patient population and the subgroup that are merlin low.

"FAK inhibition holds significant potential in malignant pleural mesothelioma, a cancer whose aggressiveness and treatment resistance proves all too often to be devastating for patients," said Dr. Joanna Horobin, Verastem Chief Medical Officer. "Development of a drug that preferentially kills cancer stem cells is a promising approach, as many standard-of-care treatments have been shown to either have no effect on, or actually enrich the population of, these chemoresistant cells."

COMMAND is expected to enroll approximately 350-400 patients at clinical sites in 11 countries, including the US, UK, Australia, Canada, South Africa, New Zealand and countries in mainland Europe. Eligible patients who had a partial response or stable disease following standard first-line therapy with platinum/pemetrexed will be stratified to merlin low or high and then randomized 1:1 to receive either placebo or 400 mg of defactinib twice daily.

"The incidence of mesothelioma, among the most aggressive and lethal cancers, is increasing worldwide, underscoring an urgent need to expand the very limited treatment options for patients fighting this disease," said Professor Dean Fennell, Chair of Thoracic Medical Oncology at the University of Leicester, incoming President of the International Mesothelioma Interest Group (iMig) and Coordinating Investigator for COMMAND in the UK. "This well-designed study is expected to deliver a one-two punch to the tumor by treating with defactinib following first-line therapy that achieves initial disease control, but has not eliminated the cancer stem cells nor historically stopped disease progression, in an attempt to prolong clinical response. There is significant enthusiasm within the mesothelioma community for the COMMAND study."

Verastem was recently granted orphan drug designation for defactinib in mesothelioma by the U.S. Food and Drug Administration's Office of Orphan Drug Products. The Company received a similar designation from the European Commission in June of this year. Adding to an intellectual property portfolio including composition of matter for defactinib, these designations provide eligibility for seven- and ten-year periods of market exclusivity, respectively, after product approval, as well as other development incentives.

"Timely initiation of this study marks yet another important milestone in our development of defactinib, and highlights the diligent execution of our clinical strategy by Verastem's research and development team," said Robert Forrester, Verastem President and Chief Executive Officer. "We will provide an update on the progress of this study in our year-end update in the first quarter of 2014."

In addition to defactinib in mesothelioma, Verastem recently announced the completion of the Phase 1 stage and initial data from an ongoing Phase 1/1b study of defactinib in combination with weekly paclitaxel for patients with ovarian cancer. Verastem expects to initiate additional studies of defactinib including a Phase 2 trial in KRAS-mutated Non-Small Cell Lung Cancer and a Phase 1 study in Japan during the third quarter of 2013. The Company also announced the recent initiation of a Phase 1 study of FAK inhibitor VS-4718 in patients with advanced cancer, and that it expects to enter the dual mTORC1/2 and PI3K inhibitor VS-5584 into the clinic later this year.

About Malignant Pleural Mesothelioma

Malignant pleural mesothelioma is an aggressive form of cancer that occurs in the mesothelium, the thin layer of tissue that covers the lungs. Mesothelioma is associated with exposure to asbestos in most cases. According to the World Health Organization, a total of 59,000 deaths occur worldwide each year due to mesothelioma. Most mesotheliomas begin as one or more nodules that progressively grow to form a solid coating of tumor surrounding the lung leading to eventual suffocation and death. A high percentage of mesotheliomas contain cancer stem cells which are generally resistant to the currently available treatment options for advanced mesothelioma.

About Defactinib

Defactinib (VS-6063) is an oral compound designed to target cancer stem cells through the potent inhibition of focal adhesion kinase (FAK). Cancer stem cells are an underlying cause of tumor resistance to chemotherapy, recurrence and ultimate disease progression. Research by Robert Weinberg, Ph.D., scientific cofounder and chair of Verastem's Scientific Advisory Board, and Verastem has demonstrated that the FAK pathway is critical for the growth and survival of cancer stem cells. Defactinib is currently being studied in a registration-directed COMMAND trial in mesothelioma and a Phase 1/1b study in ovarian cancer. A Phase 2 trial in KRAS-mutated Non-Small Cell Lung Cancer and a Phase 1 study in Japan are expected to begin in the third quarter of 2013. Defactinib has been granted orphan drug designation in the U.S. and E.U. for use in mesothelioma.

About Verastem, Inc.

Verastem, Inc. (NAS: VSTM) is discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells. Cancer stem cells are an underlying cause of tumor recurrence and metastasis. Verastem is developing small molecule inhibitors of signaling pathways that are critical to cancer stem cell survival and proliferation: FAK, PI3K/mTOR and Wnt. For more information, please visit www.verastem.com.

Forward-looking statements:

This press release includes forward-looking statements about the Company's strategy, future plans and prospects, including statements regarding the development of the Company's compounds, including VS-6063, VS-4718 and VS-5584, and the Company's FAK, PI3K/mTOR and diagnostic programs generally, the timeline for clinical development and regulatory approval of the Company's compounds, the expected timing for the reporting of data from ongoing trials, the structure of the Company's planned or pending clinical trials and estimates of the Company's ability to fund operations. The words "anticipate," "appear," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include the risks that the preclinical testing of the Company's compounds and preliminary data from clinical trials may not be predictive of the results or success of later clinical trials, that data may not be available when we expect it to be that the Company will be unable to successfully complete the clinical development of its compounds, including VS-6063, VS-4718 and VS-5584, that the development of the Company's compounds will take longer or cost more than planned, and that the Company's compounds will not receive regulatory approval or become commercially successful products. Other risks and uncertainties include those identified under the heading "Risk Factors" in the Company's Annual Report on Form 10-K for the year ended December 31, 2012 and in any subsequent SEC filings. The forward-looking statements contained in this presentation reflect the Company's current views with respect to future events, and the Company does not undertake and specifically disclaims any obligation to update any forward-looking statements.

Verastem, Inc.
Brian Sullivan, 617-252-9314
bsullivan@verastem.com

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