Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (October 2016)
20 slides from Verastem's investor presentation, Oct 3, 2016
Slide 1: Corporate Overview
CORPORATE OVERVIEW NASDAQ: VSTM October 3, 2016 Page Verastem, Inc.
Slide 2: 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'
Slide 3: The Verastem Opportunity
THE VERASTEM OPPORTUNITY target key resistance Two clinical-stage cancer mechanisms in the tumor microenvironment (TME): programs targeting multiple , , tumor types and resident Key collaborations exploring combination therapy with VSTM and leading immuno- oncology agents Well capitalized into
Slide 4: Advancing Portfolio of Cancer Programs
ADVANCING PORTFOLIO OF CANCER PROGRAMS DOSE ESC EXPANSION PHASE 2 PHASE 3 FOCAL ADHESION KINASE (FAK) PROGRAM VS-6063 – KRAS mt NSCLC Complete Ovarian; Paclitaxel combo Complete Pancreatic; Pembrolizumab + Gemcitabine Ovarian; Avelumab combo NSCLC, Panc, Meso; Pembrolizumab combo Mesothelioma; Windo
Slide 5: Clinical Experience Establishes Single Agent Activity and Combinability of FAK Inhibitors
CLINICAL EXPERIENCE TO DATE HAS ESTABLISHED SINGLE AGENT ACTIVITY AND COMBINABILITY OF FAK INHIBITORS RP2D: 400 mg BID VS-6063 Total exposure to date: 300+ patients Safety: Well tolerated and combinable; primary toxicities GI Target coverage: pFAK inhibition and decrease in CSC markers replicated in
Slide 6: Clinical Combination Focus: Targeting Key Challenges of the Tumor Microenvironment
CLINICAL COMBINATION FOCUS: TARGETING KEY CHALLENGES OF THE TUMOR MICROENVIRONMENT CANCER STEM CELLS ADAPTIVE IMMUNE RESPONSE TUMOR I-O Targeted Therapy Cytotoxic CANCER THERAPIES STROMA Stromal density = Tumor-associated fibroblasts + extracellular matrix proteins Page 6 Verastem, Inc.
Slide 7: Inhibition of FAK Has a Profound Impact on the Tumor Microenvironment
INHIBITION OF FAK HAS A PROFOUND IMPACT ON THE TUMOR MICROENVIRONMENT BOOST IMMUNE ATTACK to increase proportion of responders and duration of response REDUCE CANCER FAK inhibition reduces immune suppressive cell STEM CELLS populations in the tumor microenvironment2,4 to prevent recurrence and metas
Slide 8: FAK Inhibition Boosts Immune Attack, Supporting Combination with Immunotherapies
FAK INHIBITION BOOSTS IMMUNE ATTACK, SUPPORTING COMBINATION WITH IMMUNOTHERAPIES Serrels et al. (2015) Cell 163: 160-173 INCREASES Cytotoxic CD8+ T cells Immuno- Tumor infiltration Suppressive Cells & tumor cell killing Myeloid-derived DECREASES suppressor cells, Tregs, M2 tumor-associated macrophag
Slide 9: Tumor Burden Reduction with FAK Inhibitor Corresponds with Favorable Immune Modulation
TUMOR BURDEN REDUCTION WITH FAK INHIBITOR CORRESPONDS WITH FAVORABLE IMMUNE MODULATION Tumor burden MDSCs M2 Macrophages Tregs & Activation % of total CD4+ T cells % of total TAMs Vehicle % of total cells VS-4718 Flow cytometry Study design (n = 6-7): Cryo Day 0 10 20 RNA-Later (Cryo) VS-4718 FAK in
Slide 10: FAK + PD-1 Inhibition Synergistically Reduces Tumor Burden and Activates Immune System
FAK + PD-1 INHIBITION SYNERGISTICALLY REDUCES TUMOR BURDEN AND ACTIVATES IMMUNE SYSTEM Tumor burden Ratio: CD8 T cells/Tregs Vehicle ) 1500 3 6 p < 0 .0 0 5 M e d ia n T u m o r V o lu m e (m m M e a n , R a t io C D 8 / T r e g s 1250 VS-4718 anti-PD1 1000 4 750 500 2 250 VS-4718 + anti-PD1 0 0 0 2
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 Jiang et al. (2016) Nature Medicine 163: 851-860 STROMA CYTOTOXIC CD8+ T CELLS TUMOR FAK INHIBITORS I-O Targeted Therapy Cytotoxic CANCER THERAPIES Stromal density = Tumor-associated fibroblasts + extracell
Slide 12: FAK Inhibition Reduces Stromal Density and Boosts T Cell Entry into Pancreatic Tumors
FAK INHIBITION REDUCES STROMAL DENSITY AND BOOSTS T CELL ENTRY INTO PANCREATIC TUMORS Fibroblasts Extracellular Matrix Cytotoxic CD8+ T cells STROMAL DENSITY COMPONENTS ECM, FAP+ Fibroblasts, Fibroblast proliferation: PDAC transgenic pancreatic model, VS-4718 treatment CD8+ T cells: Kras/p53 pancrea
Slide 13: FAK Inhibitor Opens Potential for Anti-PD-(L)1 in Pancreatic Cancer
FAK INHIBITOR OPENS POTENTIAL FOR ANTI-PD-(L)1 IN PANCREATIC CANCER % Survival Days Anti-PD-1 does not increase survival FAK inhibitor increases survival either as monotherapy or as an addition to benefit of gemcitabine especially in gemcitabine or FAK inhibitor alone combination with anti-PD-1 KRas
Slide 14: FAK + Checkpoint Inhibition Enables Long Term Survival in Aggressive Pancreatic Cancer Model
FAK + CHECKPOINT INHIBITION ENABLES LONG TERM SURVIVAL IN AN AGGRESSIVE PANCREATIC CANCER MODEL Improved long term survival corresponds with increased entry of CD8+ cytotoxic T cells into tumor: CD8+ T cell infiltration Transgenic Kras/p53 KPPC pancreatic model “Immuno” = anti-PD-1 + anti-CTLA-4 + G
Slide 15: FAK Clinical Program: Newly Initiated Combination Studies in Pancreatic Cancer
FAK CLINICAL PROGRAM: NEWLY INITIATED COMBINATION STUDIES TARGETING THE TME IN PANCREATIC CANCER Phase 1b, VS-4718 + Gemcitabine + Abraxane DOSE ESCALATION (Ongoing) EXPANSION, 1ST LINE PANCREATIC (Planned) • Advanced solid tumors 1st line pancreatic Safety RP2D • 28-day cycles of VS-4718 ORR (oral
Slide 16: FAK Clinical Program: Collaboration with Pfizer and Merck KGaA to Combine VS-6063 and Avelumab
FAK CLINICAL PROGRAM: COLLABORATION WITH PFIZER AND MERCK KGAA TO COMBINE VS-6063 AND AVELUMAB Phase 1/2, VS-6063 + Avelumab (Pfizer/Merck KGaA anti-PD-L1) 3+3 DOSE ESCALATION RP2D VS-6063 (2H 2016 INITIATION) Safety • Recurrent or refractory stage III-IV EXPANSION AT RP2D ORR ovarian cancer (n = 80
Slide 17: FAK Clinical Program: Collaboration with Merck and CRUK to Combine VS-6063 and Pembrolizumab
FAK CLINICAL PROGRAM: COLLABORATION WITH MERCK AND CRUK TO COMBINE VS-6063 AND PEMBROLIZUMAB Phase 1/2, VS-6063 + Pembrolizumab (Merck anti-PD-1) EXPANSION, NSCLC (n = 15) Safety 3+3 DOSE ESCALATION RP2D VS-6063 (4Q 2016 INITIATION) ORR EXPANSION, PANCREATIC • Advanced solid tumors DOR (n = 16) • 28
Slide 18: Significant Momentum Translating FAK Mechanisms to Clinical Proof of Concept Collaborations
SIGNIFICANT MOMENTUM TRANSLATING FAK MECHANISMS TO CLINICAL PROOF OF CONCEPT COLLABORATIONS September 2015 Upcoming Upcoming2016/2017 2016/2017activities activities VS-6063 + Avelumab in Ovarian January 2016 Cancer • First patient in Q4 2016 • RP2D & initiation of expansion cohort 2017 VS-6063 +
Slide 19: Executive Management
EXECUTIVE MANAGEMENT Robert Forrester President/CEO, BOD CEO/CFO, CombinatoRx, COLY MeesPierson, Barclays, UBS Daniel Paterson Greg Berk, M.D. Chief Operating Officer Chief Medical Officer CEO, The DNA Repair Co. (now On-Q-ity) President and CMO, Sideris PharMetrics (now IMS), Axion BIND, Intellikin
Slide 20: The Verastem Opportunity
THE VERASTEM OPPORTUNITY target key resistance Two clinical-stage cancer mechanisms in the tumor microenvironment (TME): programs targeting multiple , , tumor types and resident Key collaborations exploring combination therapy with VSTM and leading immuno- oncology agents Well capitalized into