Verastem (VSTM)

[goldmansack]

Verastem Provides Year-End 2014 Update and Outlook for 2015

BOSTON--(BUSINESS WIRE)--

Verastem, Inc., (VSTM), focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, today provided an overview of the Company’s developments in 2014 and outlined upcoming milestones for 2015.

"In 2014, we achieved critical milestones across all of our development programs targeting cancer stem cells,” said Robert Forrester, President and Chief Executive Officer of Verastem. “We remain highly focused on the successful execution of COMMAND for the treatment of patients with mesothelioma, an orphan disease, with VS-6063. We currently have 55 sites open in 13 countries and have enrolled 180 patients. We expect to conduct the pre-specified interim analysis in the second quarter of 2015. We currently remain on track to complete enrollment by the end of 2015. We are seeing activity of VS-6063 across multiple tumor types, including mesothelioma, ovarian cancer, and also now in advanced non-small cell lung cancer. These results continue to increase our confidence in the potential of a successful outcome from COMMAND. Our goal is to achieve the first approval of VS-6063 in mesothelioma and then to broaden its use to many major cancers such as lung, ovarian and breast cancer.”

At the interim analysis of COMMAND, pre-specified efficacy analyses will be conducted and all safety data will be examined by the independent Data Safety Monitoring Board. A decision will be made whether to stop the study early for futility, continue the study as planned in all patients, or enrich the study population based upon the biomarker merlin. This important milestone will define the primary patient population for the registration-directed study.

“The signals of clinical activity and long-term tolerability that we are seeing across the VS-6063 program are encouraging,” said Dr. Joanna Horobin, Verastem Chief Medical Officer. “In addition, both VS-4718 and VS-5584 continue to progress well through Phase 1 clinical trials with favorable tolerability profiles and initial signs of clinical activity beginning to emerge.”

2014 Accomplishments

VS-6063 (Oral Focal Adhesion Kinase Inhibitor)

COMMAND (Control Of Mesothelioma with MAinteNance Defactinib) Study currently enrolling in 13 countries
Registration-directed, randomized, double-blind, placebo-controlled study of VS-6063 as a switch maintenance treatment in patients with malignant pleural mesothelioma benefiting from frontline therapy
Primary endpoints are Progression Free Survival (PFS) and Overall Survival (OS). A sample size of 372 subjects will provide 90% power to assess the superiority of PFS, a co-primary efficacy endpoint, with a 1 sided type I error rate of 0.025, assuming a hazard ratio of 0.67.
180 patients enrolled at 55 centers in 13 countries to date. The study is currently accruing on track to complete enrollment by the end of 2015.
So far 41% of patients have merlin low tumors, which is consistent with the Company’s assumptions
Interim analysis to define the primary patient population is expected in Q2 2015
Encouraging data from our Phase 2 clinical trial evaluating single agent VS-6063 in patients with previously treated KRAS-mutated NSCLC
Study is enrolling well at 9 U.S. sites
Accrual has completed in 2 cohorts; expect to enroll and dose the remaining cohorts in H1 2015
The two cohorts that have been fully enrolled have also crossed the interim analysis threshold of greater than or equal to 4 patients, out of 11, with greater than or equal to 12 week PFS
All cohorts have patients still on study
Long-term use is generally well tolerated
Disease control exceeding 6 months for some patients
Next steps to be determined once all cohorts are complete
Expect to submit study results for presentation at a scientific meeting in H2 2015
Reported updated Phase 1/1b data for VS-6063 in combination with paclitaxel in ovarian cancer
Combination therapy was generally well-tolerated with no dose limiting toxicities
Early signs of clinical activity; 64% best response of stable disease at 8 weeks or better including two complete responses and three partial responses
5 patients continue on study with 3 patients continuing past 12 months to date. The longest patient on study, who has had a Complete Response, has been on VS-6063 for more than 18 months
Treatment with VS-6063 resulted in decreased pFAK activity and a reduction in markers of cancer stem cells in 4 of 5 patient biopsies following 10 days of VS-6063 treatment
Expect to report an update on the study in H2 2015
Reported preliminary data from the biomarker “Window of Opportunity” study in mesothelioma
Single agent VS-6063 was given for 12 days, with pre- and post-treatment biopsies, to patients prior to surgery for malignant pleural mesothelioma
VS-6063 was well tolerated and reduced FAK activity (pFAK-Y397) by an average of 70% in patients evaluated to date and reduced markers of cancer stem cells in post-treatment biopsies in 5 out of 7 patients with evaluable paired biopsies
Measurement of tumor size using RECIST modified for mesothelioma by CT/PET confirmed that there was no progression of disease while on the 12 day treatment with VS-6063 in any of the 10 patients
Tumor shrinkage consistent with a partial response (-30% and -49%) was seen in 2 patients
The study has been amended to increase the VS-6063 treatment period from 12 to 35 days: an additional 10-15 patients are anticipated at this schedule
Expect to report preliminary data on the extended treatment cohort in H1 2016
Completed Phase 1 in Japanese patients; reported preliminary data
VS-6063 was well tolerated at all dose levels; no serious adverse events or dose-limiting toxicity
Confirmed the recommended Phase 2 dose as 400mg BID, consistent with dosing in other patient populations
Opened Japanese sites for the COMMAND study which facilitates a parallel regulatory pathway with other countries in development worldwide
The Japanese subjects included 1 patient with relapsed mesothelioma who had a symptom improvement and PFS of 5.6 months
VS-4718 (Oral Focal Adhesion Kinase Inhibitor)

Phase 1 clinical trial ongoing in patients with advanced solid tumors
Open-label, dose escalation study; designed to assess the safety, pharmacokinetics, pharmacodynamics, maximum tolerated dose and initial clinical activity of single agent VS-4718
Maximum tolerated dose has not yet been reached
Generally well tolerated with patients on treatment for over 6 months
Two patients with mesothelioma have had disease control for greater than 5 months
Expect to report preliminary data in H2 2015
Reported supportive preclinical data at AACR, EORTC, and ASH
Published supportive preclinical data in the journals Science Translational Medicine and Blood
Acquired additional license rights to VS-4718, reducing future milestones and royalties associated with ongoing development
VS-5584 (Oral Dual mTORC 1/2 and PI3K Inhibitor)

Phase 1 dose escalation clinical trial ongoing in patients with advanced solid tumors
Open-label, dose and schedule finding study; designed to assess the safety, pharmacokinetics, pharmacodynamics, maximum tolerated dose and initial clinical activity of single agent VS-5584
Generally well tolerated and the expected on-target toxicities are clinically manageable
Maximum tolerated dose has not yet been reached
Clinical activity observed in multiple tumor types, including mesothelioma; observed disease control of over 6 months
Expect to report preliminary data in H2 2015
Presented supportive preclinical data at iMig demonstrating the synergistic activities of VS-5584 and VS-6063 in cellular and animal models of mesothelioma
Planned clinical trial to evaluate combination of VS-5584 and VS-6063 in relapsed mesothelioma
Expect to begin enrollment in Q1 2015
Reported supportive preclinical data at AACR, EORTC and published supportive preclinical data in Molecular Cancer Therapeutics
Japanese patent issued with claims covering the composition of matter and VS-5584’s ability to inhibit and regulate cellular metabolism, growth, and proliferation
Leadership team

Industry veterans, Timothy J. Barberich, founder of Sepracor, and Paul A. Friedman, M.D., former CEO of Incyte Corporation (INCY), appointed to Verastem Board of Directors
Daniel Paterson, former Verastem Chief Business Officer, promoted to Chief Operating Officer
Summary of Upcoming Milestones

Verastem’s planned upcoming milestones include:

VS-6063

Report COMMAND interim analysis: Q2 2015
Report Phase 2 results in KRAS-mutated NSCLC: H2 2015
Report updated results from the VS-6063/paclitaxel combination in patients with ovarian cancer: H2 2015
Report on the biomarker “Window of Opportunity” study with preliminary results from the extended treatment cohort: H1 2016
VS-4718

Report preliminary Phase 1 results in patients with advanced solid tumors: H2 2015
VS-5584

Initiate clinical trial evaluating combination of VS-5584 and VS-6063 in relapsed mesothelioma: Q1 2015
Report preliminary Phase 1 results in patients with advanced solid tumors expected: H2 2015
Conference Call Information

The call can be accessed by dialing [phone] (U.S. and Canada) or [phone] (international), and entering passcode 60568979. To access the live slide presentation, please use either the following link: http://bit.ly/1vYH8yN or visit the investors section of the Verastem website at www.verastem.com.