Slide 1: Forward-Looking Statements
FORWARD-LOOKING STATEMENTS This presentation, and other matters discussed today, or answers that may be given to questions asked, includes forward-looking statements about the Company's strategy, future plans and prospects, including statements regarding the development and activity of the Company's
Slide 2: The Verastem Opportunity
THE VERASTEM OPPORTUNITY Multi-faceted approach to improving outcomes for patients with cancer • • • Reduce cancer stem cells Boost immune attack Reduce stromal density Two programs with clinical-stage multiple tumor types oral kinase inhibitors targeting FAK – VS-6063 and VS-4718 PI3K/mTOR – VS-558
Slide 3: Challenges in Improving Outcomes for Patients with Cancer
CHALLENGES IN IMPROVING OUTCOMES FOR PATIENTS WITH CANCER Resident cancer stem cells, limited immune response, and dense stroma contribute to the ineffectiveness of current treatments. Page Verastem, Inc.
Slide 4: Multi-Faceted Approach to Improving Patient Outcomes in Cancer
MULTI-FACETED APPROACH PATIENT OUTCOMES TO IMPROVING CANCER BOOST IMMUNE ATTACK to increase proportion of responders and duration of response3 REDUCE CANCER STEM CELLS to prevent recurrence and metastasis1,2 REDUCE STROMAL DENSITY to increase drug and immune system penetration into tumors4 1. 2. 3.
Slide 5: Reducing Cancer Stem Cells and Bulk Tumor to Improve Duration of Response
REDUCING CANCER STEM CELLS (CSC) AND BULK TUMOR TO IMPROVE DURATION OF RESPONSE Recurring tumor Tumor reduction, but CSCs survive Current therapies Initial tumor Addition of CSC-targeting agent (FAK or PI3K/mTOR) Durable response Page 6 Verastem, Inc.
Slide 6: FAK Inhibitors Shown to Reduce Cancer Stem Cells
FAK INHIBITORS SHOWN STEM CELLS TO REDUCE CANCER Ovarian mouse model (ID8) Ovarian patients, paired biopsies SOX2 RNA (CSC marker) In vivo tumor cells in ascites 2 0 1.8 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 1 5 1 0 5 0 02-306 01-316 03-302 03-301 03-315 Patient number C o n t r o l V S - 4 7 1 8 FAK Acti
Slide 7: Multi-Faceted Approach to Improving Patient Outcomes in Cancer
MULTI-FACETED APPROACH PATIENT OUTCOMES TO IMPROVING CANCER BOOST IMMUNE ATTACK to increase proportion of responders and duration of response3 REDUCE CANCER STEM CELLS to prevent recurrence and metastasis1,2 REDUCE STROMAL DENSITY to increase drug and immune system penetration into tumors4 1. 2. 3.
Slide 8: Boosting Immune Attack by Combining FAK Inhibition with Immunotherapies
BOOSTING IMMUNE ATTACK BY COMBINING FAK INHIBITION WITH IMMUNOTHERAPIES Immuno-Suppressive Cells Myeloid-derived suppressor cells, T-regs, M2 tumor-associated macrophages Cytotoxic CD8+ T cells Tumor infiltration & tumor cell killing Checkpoint inhibitor target presentation PD-L1 Treatment with FAK
Slide 9: FAK Inhibitors Produce Favorable Changes to Immune System to Decrease Tumor Burden
FAK INHIBITORS PRODUCE FAVORABLE CHANGES TO IMMUNE SYSTEM TO DECREASE TUMOR BURDEN Immunosuppressive T-regs Cytotoxic CD8+ T cells Tumor burden FAK wt Placebo Control FAK -/-Placebo Control FAK wt VS-4718 Treated FAK-wt FAK-/-FAK-wt FAK-/-Small-molecule inhibition or genetic knockout of FAK eliminat
Slide 10: Multi-Faceted Approach to Improving Patient Outcomes in Cancer
MULTI-FACETED APPROACH PATIENT OUTCOMES TO IMPROVING CANCER BOOST IMMUNE ATTACK to increase proportion of responders and duration of response3 REDUCE CANCER STEM CELLS to prevent recurrence and metastasis1,2 REDUCE STROMAL DENSITY to increase drug and immune system penetration into tumors4 1. 2. 3.
Slide 11: FAK Inhibition Reduces Stromal Density Enabling Therapies & Immune Cells to Penetrate Tumors
FAK INHIBITION REDUCES STROMAL DENSITY ENABLING THERAPIES & IMMUNE CELLS TO PENETRATE TUMORS STROMA CYTOTOXIC CD8+ T CELLS TUMOR FAK Inhibitors CANCER THERAPIES Stromal density = Tumor-associated fibroblasts + extracellular matrix proteins Verastem, Inc. Page 12
Slide 12: FAK Inhibition Reduces Stromal Density and Boosts T Cell Entry
FAK INHIBITION REDUCES STROMAL DENSITY AND BOOSTS T CELL ENTRY INTO THE TUMOR Fibroblasts Fibroblast Proliferation Extracellular Matrix Cytotoxic CD8+ T cells D. Denardo, Wash U; Jiang H et al. Focal adhesion kinase inhibition enables efficacy of checkpoint immunotherapy in pancreatic cancer EORTC 2
Slide 13: Proof of Concept: Multi-Faceted Approach to Improve Survival in Pancreatic Cancer
PROOF OF CONCEPT: MULTI-FACETED APPROACH IMPROVE SURVIVAL IN PANCREATIC CANCER TO 1. 2. 3. TARGET CSCs BOOST IMMUNE CELL RESPONSE REDUCE STROMAL DENSITY FAK Inhibitors Combined with Immuno-Oncology Therapies Improves Long term Survival in Aggressive Pancreatic Cancer VS-4718+Immuno (n=15) VS-4718 (n
Slide 14: FAK Program: Newly Initiated Combination Studies in Pancreatic Cancer
FAK PROGRAM: NEWLY INITIATED COMBINATION STUDIES IN PANCREATIC CANCER DOSE ESCALATION (Ongoing) EXPANSION, 1ST LINE PANCREATIC (Planned) 1st line ancreatic RANDOMIZATION DOSE ESCALATION (Ongoing) EXPANSION, ADVANCED PANCREATIC (Planned) Page 15 Verastem, Inc. P2D RP2D Arm 2: VS-6063 + Pembrolizumab
Slide 15: Verastem Portfolio of Cancer Programs
VERASTEM PORTFOLIO OF CANCER PROGRAMS PHASE 1 PHASE 2 PHASE 3 g term follow up up Page 16 Verastem, Inc. FOCAL ADHESION KINASE (FAK) PROGRAM VS-6063 - NSCLC; KRAS Mutant Ovarian; Paclitaxel combo Mesothelioma; Window of Opportunity Pancreatic; Pembrolizumab+Gemcitabine VS-4718 - Solid tumors Pancrea
Slide 16: VS-6063 Monotherapy in KRAS-Mutant NSCLC Showed Encouraging PFS Rates
VS-6063 MONOTHERAPY IN KRAS-MUTANT NSCLC SHOWED ENCOURAGING PROGRESSION-FREE SURVIVAL RATES 16/44 (36%) evaluable patients alive and progression free at 12 weeks Best overall response (RECIST): PR = 1; SD = 26; PD = 15; NE = 2 Median PFS 11.7 weeks, with 6 patients on study for > 6 months and 1 pati
Slide 17: VS-6063 as Single Agent Is Comparable to Targeted Agents and Docetaxel
VS-6063 AS SINGLE AGENT IS COMPARABLE TO TARGETED AGENTS AND DOCETAXEL 12 week PFS rate of experimental agents for KRAS mt NSCLC 50% 36% 40% 33% 30% 20% 10% 0% VVSS-6-600663 PPllaacebo11 GGeeffitiniibb11 SSoorraaffeenniib2 Docettaaxxeel1l1,3,3,,4 TTrraammetiniibb33 “VS-6063 was generally well tolera
Slide 18: VS-6063 Plus Paclitaxel Showed Promising Duration of Responses in Ovarian Cancer
VS-6063 PLUS PACLITAXEL SHOWED PROMISING DURATION OF RESPONSES IN OVARIAN CANCER VS-6063 can be safely combined with paclitaxel 41% (9/22) disease control (objective response or SD > 6 months; 2 CR; 3 PR; 4 SD > 6 months) CR 03-202 SD 01-310 SD 02-314 PR 03-315 PR 03-301 SD 01-308 CR 03-102 SD 01-30
Slide 19: Durable Complete Response Shows Potential for FAK Inhibition
DURABLE COMPLETE RESPONSE SHOWS POTENTIAL FOR FAK INHIBITION TO “FINISH THE JOB” Patient 03-202: Stage IV platinum-resistant serous ovarian cancer with 5 prior lines of therapy Stable disease (SD) with combination treatment 1 VS-6063 2 Complete response (CR) 3 Continues to tolerate VS-6063 well mono
Slide 20: VS-5584, a Pan-PI3K/mTOR Inhibitor, Moving Into Ovarian and Heme Expansion Cohorts
VS-5584, A PAN-PI3K/MTOR INHIBITOR, WILL BE MOVING SHORTLY INTO OVARIAN AND HEME EXPANSION COHORTS • VS-5584 is equipotent against mTORC1, mTORC2 and all four PI3K class I isoforms 50 • Combined inhibition of PI3K and mTOR is critical to CSC targeting1 Planned expansion cohorts at RP2D in ovarian &
Slide 21: 2016 Milestones
2016 MILESTONES Planned initiation in 2016 PHASE 1 / 1B PHASE 2 PHASE 3 g term follow up nsion in NSCLC cer ose escalation markers nsion in advanced ed biopsies nsion in 1st line nsion in Data Readouts in 2016 and 2017 Page 22 Verastem, Inc. FOCAL ADHESION KINASE (FAK) PROGRAM VS-6063 - NSCLC; KRAS
Slide 22: Executive Management and Board of Directors
EXECUTIVE MANAGEMENT Robert Forrester Daniel Paterson President/CEO, BOD CEO/CFO, CombinatoRx/COLY MeesPierson, Barclays, UBS Chief Operating Officer CEO: The DNA Repair Co. (now On-Q-ity) PharMetrics (now IMS), Axion Steven Bloom VP, Corporate Development VP, Commercial Strategy and Business Develo
Slide 23: The Verastem Opportunity
THE VERASTEM OPPORTUNITY Multi-faceted approach to improving outcomes Clinical programs targeting multiple cancers Experienced team Well capitalized with strong IP Page 24 Verastem, Inc. $120.1M IN CASH AND CASH EQUIVALENTS AS OF SEPT. 30, 2015 Sufficient operating capital into 2018 Intellectual Pro
Slide 24: The Verastem Opportunity
THE VERASTEM OPPORTUNITY Multi-faceted approach to improving outcomes Clinical programs targeting multiple cancers 00st MMUNE ATTACK neouce CANCER voce ‘STEM CELLS reouce STROMAL DENSITY os \VERASTEM PORTFOLIO OF CANCER PROGRAMS Experienced team Well capitalized with strong IP. ‘EXECUTIVE MANAGEMENT