Verastem Presents Results and Updated Development Plans

Verastem, Inc., VSTM focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, today hosted its annual Research and Development Day at the Harvard Club in New York, NY. Members of the Verastem leadership team provided an overview of the Company's development programs targeting cancer stem cells through the inhibition of focal adhesion kinase (FAK) and PI3K/mTOR signaling pathways. Guest speakers for the event included Robert Weinberg, Ph.D., Whitehead Institute and Verastem scientific cofounder and chair of the Scientific Advisory Board, Jose Baselga, M.D., Ph.D., Physician in Chief, Memorial Sloan-Kettering Cancer Center and Verastem Scientific Advisory Board member, and Richard Gralla, M.D., Albert Einstein College of Medicine and Verastem Mesothelioma Steering Committee member. “While research in oncology has made progress in the clinical outcome for a subset of patients, this has been primarily in tumors with a defined genetic mutation,” said Dr. Baselga. “Verastem is pioneering a comprehensive approach by combining inhibitors of cancer stem cells with chemotherapy, either concurrently or in sequence as a maintenance treatment, which may provide a path to a more durable clinical response in patients with cancer.” Verastem's lead compound is VS-6063, an orally available agent that targets cancer stem cells through potent inhibition of FAK. Dr. Weinberg presented preclinical data that demonstrates the critical nature of the FAK pathway in the development and survival of cancer stem cells. Cancer stem cells are an underlying cause of tumor resistance to chemotherapy, recurrence and ultimate disease progression. “We have built upon the scientific foundation outlined by Dr. Weinberg's work in oncology,” said Robert Forrester, Verastem President and Chief Executive Officer. “The diligent execution by our research and development team continues to advance Verastem's portfolio of cancer stem cell targeting agents through clinical development. Two portfolio compounds, VS-6063 and VS-4718, have now entered clinical development and we plan to enter our third compound, the dual mTORC1/2 and PI3K inhibitor VS-5584, into the clinic later this year. Our intent is to have three candidates in six clinical trials ongoing in parallel by the end of 2013.” Verastem reported the completion of the Phase 1 portion of a Phase 1/1b study of VS-6063 in combination with paclitaxel for the treatment of patients with ovarian cancer. “The combination of VS-6063 and paclitaxel was well tolerated at all doses with no exacerbation of the well-known adverse effects of paclitaxel,” said Dr. Joanna Horobin, Verastem Chief Medical Officer. “This result allows us to explore this combination for treatment in a wide range of cancers where paclitaxel is commonly used. In this early stage of the trial, we also observed a significant decrease in the CA-125 biomarker in several patients, and one patient, now in her fourth cycle, has had a complete response in her CA-125, which has returned to normal levels. In addition she had a radiological complete response at the end of cycle 2 which will be reconfirmed at the end of cycle 4. We are encouraged by this early sign of activity.” Verastem outlined detailed plans for a registration-directed clinical study of VS-6063 in patients with malignant pleural mesothelioma, a form of lung cancer with a high percentage of cancer stem cells, planned to initiate in the third quarter of 2013. This study is designed as an adaptive, double-blind, placebo-controlled trial. Verastem has identified a biomarker called merlin that is present in approximately 50% of mesothelioma cancers. Low merlin levels enhance the effect of FAK inhibition, and Verastem presented the stratified trial design to evaluate the effect of VS-6063 in both the overall patient population and the subgroup that are merlin-low. The Primary endpoints are Progression Free Survival (PFS) and Overall Survival (OS), with potential for accelerated approval on PFS. The international mesothelioma study is expected to enroll approximately 350-400 patients at clinical sites in 11 countries including the US, Canada, Europe, Australia, New Zealand and South Africa. Verastem has received allowance in the US, UK and Belgium to initiate the trial and is working with the regulatory agencies worldwide to receive full allowance to proceed. The company also expects to initiate a Phase I bridging study in the third quarter of 2013 to include Japanese sites in the registration-directed mesothelioma study by the end of 2014. “Our mission is to develop new medicines that provide a meaningful improvement in cancer care for patients,” said Christoph Westphal, M.D., Ph.D., Verastem Executive Chairman. “Through our focus on targeting cancer stem cells, we continue to work diligently to bring new treatment options to patients with mesothelioma and ovarian cancer, and ultimately to patients with other cancers as well.” As part of its goal to expand into other cancers, Verastem also outlined plans for an upcoming Phase 2 trial of VS-6063 in KRAS-mutated Non-Small Cell Lung Cancer. Mutations in the KRAS gene are found in approximately 50 percent of Non-Small Cell Lung Cancers, and KRAS-mutated lung cancer, accompanied by a second mutation in INK4a/ARF or p53, has been shown to be especially sensitive to FAK inhibition. The planned study will include four arms to evaluate the effect of VS-6063 in different combinations of these mutations. Research and Development Day Program Highlights: Focal Adhesion Kinase (FAK) Inhibition FAK is a critical regulator of cancer stem cells and disease progression VS-6063 Completed the Phase 1 portion of a Phase 1/1b trial of VS-6063 in combination with paclitaxel in patients with ovarian cancer and opened the Phase 1b portion of trial Combination was well tolerated at all dose levels Recommended Phase 2 dose was determined to be 400mg BID in combination with weekly paclitaxel Observed significant decrease in CA-125 biomarker in several patients, including one patient, now in her fourth cycle, with a CA-125 complete response and radiological complete response at the end of cycle 2, to be reconfirmed at the end of cycle 4 Expect to initiate a registration-directed randomized, double blind, placebo controlled study in malignant pleural mesothelioma in Q3 2013 Received allowance in the US, UK and Belgium and working with regulatory agencies in 11 countries to open the study Outlined the specific trial design with a stratification and adaptive enrichment design based on the biomarker merlin Expected to enroll 350-400 patients Primary endpoints to include PFS and OS, with potential for accelerated approval on PFS Study powered for PFS (90%), with option to resize at primary PFS analysis to ensure appropriate power for OS Expect to initiate a Phase 1 bridging study in advanced solid tumors in Japan in Q3 2013 Goal is to facilitate inclusion of Japanese sites in the global mesothelioma trial by YE 2014 Expect to initiate a clinical trial in NSCLC in Q3 2013 Received orphan designation in Europe and filed for orphan designation in the U.S. for the use of VS-6063 in mesothelioma VS-4718 Started a Phase 1 clinical trial in patients with advanced cancer with the study expected to enroll up to 40 patients at three U.S. locations Dual PI3K/mTOR Inhibition PI3K and mTOR are key enzymes in the AKT signaling pathway that promote cancer stem cell proliferation and survival VS-5584 Oral formulation; potent against mTORC1/2 & all Class 1 PI3K isoforms, and demonstrated preclinical selectivity for cancer stem cells IND-enabling toxicity studies ongoing Expect to initiate Phase 1 dose escalation in patients with advanced solid tumors and lymphomas in Q4 2013 Webcast Replay Information A replay of the webcast will be archived on the Verastem website at www.verastem.com for 90 days following the presentation date. About Verastem, Inc. Verastem, Inc. 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.