Verastem, Inc. · NASDAQ:VSTM
Verastem — J.P. Morgan Healthcare Conference 2020
51 slides from Verastem's conference presentation, Jan 13, 2020
Slide 1: Corporate Overview | J.P. Morgan Healthcare Conference
PROPERTY OF VERASTEM, INC. 1 Corporate Overview | J.P. Morgan Healthcare Conference | January 13, 2020 Verastem Oncology
Slide 2: Safe Harbor Statement
2 2 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION Safe Harbor Statement This presentation includes forward-looking statements about, among other things, Verastem Oncology’s products and product candidates, including anticipated regulatory submissions, approvals, performance and
Slide 3: Corporate Overview
PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION ▪ The first-approved oral inhibitor of PI3K-δ and PI3K-γ ▪ Exclusively marketed in the US by Verastem Oncology ▪ Partnered in Japan, China, Russia/CIS, Turkey, Middle East, & Africa Full prescribing information, including BOXED WARNI
Slide 4: The Verastem Corporate Plan
4 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 4 • Broaden indications for COPIKTRA® • Additional marketed products • Robust pipeline of assets in development • Achieve cash flow break even for both the commercial and clinical COPIKTRA® program • Refocused commercial efforts on
Slide 5: 2019 Recap Corporate and Financial
5 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 2019 Recap Corporate and Financial ✓ FY19 Revenue Guidance in the range of $12-$14M ✓ Refinanced Hercules Loan Facility ✓ Appointed Brian Stuglik as CEO ✓ Signed Exclusive License Agreement with Sanofi for the Development and Comme
Slide 6: 2020 Milestones
6 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 6 2020 Milestones COPIKTRA® ❑ NCCN Guidelines – PTCL ❑ Complete Accrual on PRIMO ❑ Japan First Patient In – PRIMO ❑ DUV + I/O – First Patient In, Safety Data ❑ Updates on multiple ISTs ❑ Clinical Data on FAK + MEK in 1H 2020 ❑ Clin
Slide 7: Key Financial Statistics
7 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 7 Key Financial Statistics QTD Net Revenue as of 9/30/2019 $9.0M Cash, cash equivalents & investments as of 9/30/2019 $160.2M Shares outstanding as of 9/30/2019 74.3M Shares fully diluted as of 9/30/2019 112.6M Hercules Term Loan F
Slide 8: Refinancing of Convertible Senior Notes due 2048
8 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION Refinancing of Convertible Senior Notes due 2048 $63M $150M $36M $35M $35M $- $20 $40 $60 $80 $100 $120 $140 $160 $180 $200 Ending Sep 30, 2019 Post Exchange Sr. Secured Notes Issued Oct 2018 Exchange Notes Issued Nov 2019 $51M $13
Slide 9: Senior Management Team
9 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 9 Senior Management Team Daniel Paterson President and Chief Operating Officer CEO - The DNA Repair Co. (now On-Q-ity) PharMetrics (now IMS), Axion Cathy Carew Chief People & Organizational Strategy Officer Principal - HR Collabora
Slide 10: COPIKTRA / Duvelisib
PROPERTY OF VERASTEM, INC. 10 COPIKTRA® / Duvelisib
Slide 11: Building a Global Brand: COPIKTRA Global Expansion Strategy
11 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 11 Building a Global Brand COPIKTRA® Global Expansion Strategy Regional license $15M Up-front $160M Development and Sales milestones Double digit royalty CHINA JAPAN Regional license $10M Up-front $90M Development and Sales milest
Slide 12: Changes in Execution to Shift the Launch Trajectory
12 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 12 Optimize Accelerate Expand • Moving to Account Based Selling • Upgrading and flattened Field Organization for improved account access and experience • Shifting focus to efficacy based messaging • Improving Thought Leader suppor
Slide 13: Grow COPIKTRA Through Clinical Expansion
13 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 13 Grow COPIKTRA® Through Clinical Expansion Sources: 1. Copiktra USPI, 2018 – Accelerated Approval in FL, Full approval in CLL/SLL; 2. Decision Resources, US 2018 Monotherapy for R/R FL and CLL/SLL after 2 Prior Lines 1 FL: 13,00
Slide 14: Duvelisib Pipeline – PI3K Delta / PI3K Gamma Inhibitor
14 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 14 PHASE 1 / 1B PHASE 2 PHASE 3 COLLABORATOR Company Sponsored Trials Relapsed/Refractory CLL/SLL Randomized open label vs. ofatumumab Refractory iNHL Single arm, monotherapy Relapsed/Refractory PTCL Single arm, monotherapy Relaps
Slide 15: Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL)
15 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 15 Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL) • Median OS is < 6 months1 • NCCN guidelines still recommend clinical trials for relapsed patients2 • KOLs are unsatisfied with the available treatment options Drug / Trial
Slide 16: PRIMO Overview: Optimal Dose Decision
16 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 16 PRIMO Overview: Optimal Dose Decision ClinicalTrials.gov Identifier: NCT03372057 Patient population • Includes all common PTCL sub-types • For PTCL, minimum one prior therapy • No maximum limit of prior therapies • For CD30+ AL
Slide 17: Phase 1/2 Study of Duvelisib and Venetoclax in CLL/SLL
17 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 17 Phase 1/2 Study of Duvelisib and Venetoclax in Patients with Relapsed or Refractory CLL/SLL • No DLTs observed • SAEs (all grade 3): Asymptomatic elevation in amylase and/or lipase (n=2), febrile neutropenia (n=1), pneumonia (n
Slide 18: Duvelisib Synergistic with PD-1 and OX40 Antibodies in Preclinical Model
18 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 18 Duvelisib is synergistic with PD-1 and OX40 antibodies in B-cell lymphoma (A20) preclinical model • Duvelisib @ 50 mg/kg po, BID • Anti-OX40 @ 100 mg/mouse ip, biweekly x 2 • Duvelisib @ 50 mg/kg po, BID • Anti-PD-1 @ 100 mg/mo
Slide 19: Ph 1b/2 I-O Combination Trial in HNSCC
19 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 19 Ph 1b/2 I-O combination trial in HNSCC ▪ Stage 1 Primary Objective: Determine safety & tolerability of duvelisib in combination with pembrolizumab (Keytruda®1, anti-PD-1) in recurrent/ metastatic head and neck squamous cell car
Slide 20: Additional Therapy Options are Needed for Chronic iNHL Patients
20 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 20 Opportunity: Additional Therapy Options are Needed for Chronic iNHL Patients FL US PREVALENCE 20181 141,000 13,500 22,205 CLL/SLL US PREVALENCE 20181 197,000 1ST LINE TREATABLE PATIENTS/YEAR (AVG.)1 65-75 AGE AT DIAGNOSIS2 MEDI
Slide 21: COPIKTRA for CLL/SLL: Progression-free Survival
21 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 21 COPIKTRA® for CLL/SLL Patients with at Least 2 Prior Therapies Progression-free Survival (COPIKTRA vs. Ofatumumab) PFS per IRC in Patients with at Least 2 Prior Therapies (N = 196) COPIKTRA is approved for the treatment of adul
Slide 22: COPIKTRA for CLL/SLL: PFS Analysis by Selected Variables
22 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 22 COPIKTRA® for CLL/SLL Patients with at Least 2 Prior Therapies PFS Analysis by Selected Variables PFS Analysis in High-Risk Patient Subgroups (N = 196)* COPIKTRA is approved for the treatment of adult patients with relapsed or
Slide 23: COPIKTRA for CLL/SLL: ORR and LNRR
23 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 23 COPIKTRA® for CLL/SLL Patients with at Least 2 Prior Therapies ORR and LNRR Overall Response Rate (ORR) per IRC1 Lymph Node Response Rate (LNRR) per IRC 2 Data were evaluated based on the International Workshop on CLL or revise
Slide 24: FL: Data Supporting Accelerated Approval
24 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 24 Outcome per IRC FL N = 83 ORR, n (%) a 35 (42%) 95% CI (31, 54) CR, n (%) 1 (1%) PR, n (%) 34 (41%) Duration of response Range, months 0.0+ to 41.9+ Patients maintaining response at 6 months, n/N (%) 15/35 (43%) Patients mainta
Slide 25: Pooled Analysis of Safety Supporting Approval
25 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 25 † Grouped term for reactions with multiple preferred terms a Diarrhea or colitis includes the preferred terms: colitis, enterocolitis, colitis microscopic, colitis ulcerative, diarrhea, diarrhea hemorrhagic b Pneumonia includes
Slide 26: FAK and RAF/MEK Program Targeting KRAS Mutant Cancers
26 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION FAK and RAF/MEK Program Targeting KRAS Mutant Cancers
Slide 27: Defactinib + CH5126766: Potential Best-in-Class Combination
27 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 27 Defactinib + CH5126766: Potential Best-in-Class Combination for RAS/RAF-Mutant Cancers ▪ Defactinib and CH5126766 have each shown independent clinical activity in RAS mutant cancers ▪ MEK blockade activates pFAK as a potential
Slide 28: Licensing Transaction Potentially Transformative for Verastem Oncology
28 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 28 This licensing transaction and combination of defactinib + CH5126766 are potentially transformative for Verastem Oncology ▪ This transaction is aligned with and supports our 6-2-5 strategy to build a company with multiple produ
Slide 29: Ongoing Investigator-Sponsored Basket Study of CH5126766 + Defactinib
29 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 29 Ongoing Investigator-Sponsored Basket Study of CH5126766 + Defactinib in KRAS-mutant Cancers Phase I Advanced Solid Cancers • CH5126766 oral twice wkly x 3 every 4 wks • Defactinib oral BID daily x 3 wks q 4 wks • 3 cohorts inc
Slide 30: Defactinib Pipeline – FAK Inhibitor
30 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 30 Defactinib Pipeline – FAK Inhibitor PHASE 1 / 1B PHASE 2 PHASE 3 COLLABORATOR Investigator Sponsored Trials NSCLC, Pancreatic, Mesothelioma With Pembrolizumab Resectable Pancreatic Ductal Adenocarcinoma With Pembrolizumab Pancr
Slide 31: High Unmet Need in RAS/RAF/MEK/ERK-Driven Cancers
31 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 31 ▪ 30 percent of all human cancers are driven by mutations of the RAS family of genes ▪ Patients with mutations of the RAS family have an overall worse prognosis ▪ Multiple approaches (direct targeting, blocking downstream signa
Slide 32: The Importance of RAS Pathway in Human Cancers
32 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 32 The Importance of RAS Pathway in Human Cancers Common Mutations in Many Large Cancer Types References: 1. Reference for RAS mt frequencies – Cox et al. Nature Reviews 13: 828, 2014 2. Reference for KRAS mt in LGSOC – Grisham AS
Slide 33: KRAS Mutation Status: % Frequency by Tumor Type
33 CONFIDENTIAL. Do Not Distribute. © Verastem Inc. 2018 33 KRAS mutation status: % frequency by tumor type Source: TCGA Database Lung Adenocarcinoma Colorectal Adenocarcinoma Pancreatic Adenocarcinoma Uterine Endometrioid Carcinoma G12C G12V G12D G12A G13C G12S G13D 0 5 10 15 NSCLC Adenocarcinoma 1
Slide 34: FAK is Critical for Multiple Aspects of Tumor Progression
34 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 34 ▪ Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase that mediates signaling downstream of integrins & growth factor receptors ▪ Plays key roles in metastasis and drug resistance ▪ Immuno-Oncology/Tumor Microenvironm
Slide 35: Defactinib (VS-6063) – Selective FAK Inhibitor
35 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 35 Defactinib (VS-6063) – Selective FAK Inhibitor p F A K ( Y 3 9 7 ; H S c o r e ) D a y 1 D a y 1 0 0 5 0 1 0 0 1 5 0 Pre-treatment Post-treatment pFAK (Y397; H - Score) * 03-315 OVARIAN CANCER: TUMOR BIOPSIES MESOTHELIOMA: TUMO
Slide 36: Clinical Activity of Defactinib Monotherapy in KRAS Mutant NSCLC
36 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 36 Clinical Activity of Defactinib Monotherapy in KRAS mutant NSCLC Control siRNA FAK (2) siRNA FAK (1) Mutant INK4a/ARF NSCLC Oncogenic KRAS wt KRAS Mutant p53 NSCLC Oncogenic KRAS wt KRAS KRAS mt is necessary for sensitivity to
Slide 37: Targeting FAK Overcomes Key Resistance Mechanisms to BRAF & MEK Inhibitors
37 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 37 ▪ MEK inhibition induces compensatory activation of pFAK preclinically and clinically (Banerji, BTOG 2019) ▪ BRAF & MEK inhibitors can block Growth Factor-stimulated ERK signaling, but Cell Attachment can also stimulate ERK sig
Slide 38: Screen for Synergy with Defactinib Identified MEK Inhibitors
38 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 38 Screen for Synergy with Defactinib Identified MEK Inhibitors (& CH5126766) as Top Hit TOV-21G CELLS KRAS-MUTANT OVARIAN CANCER Defactinib Defactinib + Trametinib Loewe Model H441 CELLS KRAS-MUTANT NON-SMALL-CELL LUNG CANCER Def
Slide 39: CH5126766 is a Unique Small Molecule RAF/MEK Inhibitor
39 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 39 ▪ CH5126766 uniquely inhibits both MEK kinase and RAF kinase activities ▪ Standard MEK inhibitors (e.g. PD0325901) paradoxically induce MEK phosphorylation (pMEK) by relieving ERK- dependent feedback inhibition of RAF which may
Slide 40: CH5126766 is Effective Against Multiple RAS & RAF Mutations
40 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 40 CH5126766 is effective against multiple RAS & RAF mutations: Potential to act more broadly or be combined with agents targeting specific mutations only Reference: Ishii et al., Cancer Research, 2013 PD0325901 (mirdametinib) is
Slide 41: Background: CH5126766
41 Background Presented by: Maxime Chénard-Poirier, MD • CH5126766: MEK inhibitor with functional pan-RAF inhibition, first-in-class agent • Dose escalation by Martinez-Garcia et al. 2012 • MTD 2.25 mg, once daily • MTD 4.0 mg, 4 days on/3 days off • MTD 2.7 mg, 7 days on/7 days off • Promising acti
Slide 42: Background: Dose Escalation Design
42 Background Presented by: Maxime Chénard-Poirier, MD • In view of promising activity, a different trial design was investigated to mitigate toxicity • Mean terminal t1/2 of ≈ 60 hours • 2x-weekly and 3x-weekly scheduling, in 4 week cycles • Led by the Drug Development Unit at RMH/ICR 4.0mg 2x week
Slide 43: Adverse Events
43 Adverse Events Presented by: Maxime Chénard-Poirier, MD Adverse event details Expansion: 4mg 2x weekly n=26 Martinez-Garcia et al. CCR 2012 Patient treated at OD MTD n=6 All grades ≥ Gr. 3 ≥ Gr. 3 Rash-related 22 (84.6 %) 5 (19.2 %) 3 (50.0 %) CK elevation 15 (57.7 %) 2 (7.6%) 1 (16.7 %) Blurred
Slide 44: Results: KRASmut NSCLC - Adenocarcinoma
44 Results: KRASmut NSCLC - Adenocarcinoma Presented by: Maxime Chénard-Poirier, MD Progression Free Survival Best response by RECIST v1.1 .. . . . . . . . . . -8 0 -6 0 -4 0 -2 0 0 2 0 1 9 0 0 -2 2 -3 8 -4 4 -6 8 -8 -1 4 5 B e s t R e s p o n s e % c h a n g e f r o m b a s e l i n e K R A S m u t
Slide 45: Results: Gynaecological Cancers
45 Results: Gynaecological cancers Presented by: Maxime Chénard-Poirier, MD Progression Free Survival Best response by RECIST v1.1 .. . . . . -8 0 -6 0 -4 0 -2 0 0 2 0 4 1 -3 0 -4 8 -6 5 B e s t R e s p o n s e % c h a n g e f r o m b a s e l i n e O v a ria n (K R A S m u t ) O v a ria n (B R A F m
Slide 46: Conclusion
46 Conclusion • CH5127566 (RO5126766) is a potent and well-tolerated RAF-MEK inhibitor • Twice-weekly scheduling improved therapeutic index • Multiples responses in KRAS- and BRAF-mutated malignancies, with impressive results in NSCLC and gynaecological cancers • Preliminary results suggesting singl
Slide 47: KRASM MEK + FAK Inhibitor Combinations
PROPERTY OF VERASTEM, INC. 47 KRASM MEK + FAK inhibitor combinations Phosphoproteomic signature of KRASM A549 NSCLC cell line exposed to Trametinib for 1hr shows feedback loops involving FAK Serrels A Cell 2015, 163:160-173
Slide 48: Tumor Regression with FAK + RAF/MEK Combination in Ovarian Xenograft Model
PROPERTY OF VERASTEM, INC. 48 48 Tumor regression achieved with FAK + RAF/MEK Combination in KRAS-mutant Ovarian Xenograft Model (TOV21G)
Slide 49: Supporting Materials
49 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 49 Supporting Materials
Slide 50: Selected Important Safety Information
PROPRIETARY – NOT TO BE REPRODUCED 50 Indication Dosing & Administration Selected Important Safety Information WARNING: FATAL AND SERIOUS TOXICITIES: INFECTIONS, DIARRHEA OR COLITIS, CUTANEOUS REACTIONS, and PNEUMONITIS ▪ Fatal and/or serious infections occurred in 31% of COPIKTRA-treated patients.
Slide 51: Reconciliation of GAAP to Non-GAAP Financial Information
51 PROPERTY OF VERASTEM, INC. – NOT FOR DISTRIBUTION OR DISSEMINATION 51 Verastem, Inc. Reconciliation of GAAP to Non-GAAP Financial Information (in thousands, except per share amounts) (unaudited) Three months ended September 30, Nine months ended September 30, 2019 2018 2019 2018 Net Loss Reconcil