Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (August 2020)
33 slides from Verastem's investor presentation, Aug 10, 2020
Slide 1: Corporate Overview August 10, 2020
Corporate Overview August 10, 2020 NASDAQ: VSTM
Slide 2: Safe Harbor Statement
2 PROPERTY OF VERASTEM INC. This presentation includes forward - looking statements about, among other things, Verastem Oncology’s products and product candidates, including anticipated regulatory submissions, approvals, performance and potential benefits of Verastem Oncology products and product ca
Slide 3: Investigational Research & Pipeline Portfolio Targets Opportunities with High Unmet Need
3 PROPERTY OF VERASTEM INC. Investigational Research & Pipeline Portfolio Targets Opportunities with High Unmet Need VS - 6766 Program Defactinib Program First in Class Investigational RAF/MEK inhibitor Acquired WW Rights from Chugai in Jan - 20 Activity in KRAS Mutant Tumors Novel Dosing Schedule F
Slide 4: Biopharmaceutical company developing new medicines for patients battling cancer
4 PROPERTY OF VERASTEM INC. We are a biopharmaceutical company committed to developing and commercializing new medicines for patients battling cancer VS - 6766 (RAF/MEKi) and defactinib (FAKi) are clinically active against KRAS mutant cancers 30% of all human cancers are driven by mutations in RAS f
Slide 5: COPIKTRA sale to Secura Bio: total deal value up to $311 million
5 PROPERTY OF VERASTEM INC. Total Deal Value up to $311 million $70 million upon closing of the transaction A total of $45 million from two separate milestones for U.S. FDA and EMA Approvals of COPIKTRA® with label indicated for Peripheral T - cell lymphoma A total of $50 million for cumulative worl
Slide 6: RAS Pathway: Current Approaches and Unmet Needs & Defactinib
RAS Pathway: Current Approaches and Unmet Needs VS - 6766 & Defactinib: Novel targeted therapies for high unmet medical need cancers
Slide 7: High Unmet Needs in RAS/RAF/MEK/ERK-Driven Cancers
7 PROPERTY OF VERASTEM INC. NSCLC Incidence 3,5 : 194K Colorectal Incidence 5 : 105K Pancreatic Incidence 5 : 58K Uterine Endometrioid Incidence 4,5 : 59K Melanoma Incidence 5 : 108K Multiple Myeloma Incidence 5 : 32K Melanoma Incidence 5 : 108K Ovarian Incidence 5 : 22K Papillary Thyroid Incidence
Slide 8: Unique Small Molecule RAF/MEK Inhibitor
8 PROPERTY OF VERASTEM INC. VS - 6766 inhibits both MEK & RAF kinase activities MEK inhibitors paradoxically induce MEK phosphorylation (pMEK) by relieving ERK - dependent feedback inhibition of RAF VS - 6766 is a Unique Small Molecule RAF/MEK Inhibitor Reference : Ishii et al., Cancer Res , 2013; L
Slide 9: Compelling Preclinical Synergy Observed with RAF/MEKi + FAKi Combination
9 PROPERTY OF VERASTEM INC. Defactinib Defactinib + Trametinib Loewe Model Compelling Preclinical Synergy Observed with RAF/MEKi + FAKi Combination Coma and Pachter, Verastem (unpublished) Trametinib ( MEKi ) Vehicle FAKi VS - 6766 VS - 6766 + FAKi FAKi PLX4720 (BRAFi) BRAFi + FAKi Vehicle H441 CEL
Slide 10: More Complete Shutdown of Tumor Growth Requires Addressing Multiple Resistance Mechanisms
10 PROPERTY OF VERASTEM INC. RTK RAS RAF MEK ERK RhoA Growth factors β α Y397 Integrin FAK ECM SRC YAP Proliferation/Survival/Migration P BRAF inhibition induces compensatory activation of pFAK 1 MEK inhibition induces compensatory activation of pFAK preclinically and clinically 2 ▪ Trametinib induc
Slide 11: Low Grade Serous Ovarian Cancer (LGSOC) Opportunity for Precision Medicine
Low Grade Serous Ovarian Cancer (LGSOC) Opportunity for Precision Medicine
Slide 12: 50% of LGSOC Have KRAS/NRAS/BRAF Mutations
12 PROPERTY OF VERASTEM INC. LGSOC (KRASm in 25% of patients) KRASm , 25.4% NRASm , 13.5% BRAFm , 11.1% Wild - Type , 50.0% Incidence 10 Yr Prevalence Worldwide ~13,000 ~80,000 US ~1,000 ~6,000 *Based on LGSOC representing 5% of epithelial ovarian cancer 50% of LGSOC Have KRAS/NRAS/BRAF Mutations* T
Slide 13: LGSOC: Limited Treatment Options With High Unmet Need
13 PROPERTY OF VERASTEM INC. Platinum based chemotherapy ORR=~10% 13% ORR for letrozole MEK inhibitors in the range of approx. 15 - 25% with high toxicities Low - Grade Ovarian Cancer – Treatment Algorithm 1 Stage IA - IB Stage IC Stage II - IV Observe only Pt Chemo Combo: Carbo - Pt + Paclitaxel (p
Slide 14: FRAME: Focusing on Low Grade Serous Ovarian Cancer
14 PROPERTY OF VERASTEM INC. FRAME 1 : Focusing on Low Grade Serous Ovarian Cancer *Refractory to conventional treatment or for which no conventional treatment exists a Includes one KRASm mucinous ovarian carcinoma b Non LGSOC or NSCLC phase 1 patients included to determine recommended dose or PD mo
Slide 15: Adverse Event Details
15 PROPERTY OF VERASTEM INC. Dose Escalation Phase Dose Expansion Phase Adverse Event Details* VS - 6766 3.2mg Def 200mg Cohort 1 n=3 VS - 6766 4mg Def 200mg Cohort 2a n=6 VS - 6766 3.2mg Def 400mg Cohort 2b n=3 VS - 6766 3.2mg Def 200mg Cohort 1 n=17 VS - 6766 4mg Def 200mg Cohort 2a n=17 Total N=4
Slide 16: Initial Results in Combination with Defactinib Shows Robust ORR in KRASm Refractory LGSOC
16 PROPERTY OF VERASTEM INC. 0 12 24 36 48 60 72 84 96 108 FRA101015 FRA101012 FRA101007 FRA101019 FRA101014 FRA101009 FRA101002 FRA101001 Time on Treatment (Weeks) * * * * * G12D G12D G12V G12D G12A G12V WT WT Confirmed Responses By RECIST • 67% ORR (4/6) FOR KRASm LGSOC; All LGSOC ORR = 50% (4/8)
Slide 17: Monotherapy Shows Activity Across RAS Pathway Mutations in Refractory Gynecologic Cancers
17 PROPERTY OF VERASTEM INC. VS - 6766 Monotherapy Shows Activity Across RAS Pathway Mutations in Refractory Gynecologic Cancers Endometrial ( KRAS mut ) Ovarian ( KRAS mut ) Ovarian ( KRAS mut ) Endometrial ( KRAS mut ) Ovarian ( BRAF mut ) Best Response by RECIST v1.1 Progression Free Survival * *
Slide 18: Phase 2 Recurrent LGSOC Adaptive Design for Potential Accelerated Approval
18 PROPERTY OF VERASTEM INC. KRAS Mutated (mt) and Wild Type ( wt ), Phase 2, Recurrent LGSOC Adaptive Design for Potential Accelerated Approval *Selection Phase – KRAS mt only **Expansion Phase – final sample size to be adjusted based on adaptive design • Recurrent LGSOC • Measurable disease (RECIS
Slide 19: Proof of Concept Established in LGSOC: Key Takeaways and Next Steps
19 PROPERTY OF VERASTEM INC. Present additional data from the LGSOC cohort of the FRAME study in September Commence Phase 2 Registration - Directed Trial by the end of 2020 Proof of Concept Established in LGSOC VS - 6766 ± Defactinib Represents Best in Class Market Opportunity in LGSOC 1 http://mole
Slide 20: NSCLC Opportunity Additional Opportunity for Precision Medicine
NSCLC Opportunity Additional Opportunity for Precision Medicine
Slide 21: High Unmet Need in Refractory KRASm NSCLC Adenocarcinoma
21 PROPERTY OF VERASTEM INC. 0 5 10 15 G12C G12V G12D G12A G13C G12S G13D % of Patients KRAS Mutation Advanced or Metastatic NSCL Cancer Recommend Histologic and Molecular Subtyping 5 Appropriate targeted agent Chemotherapy Docetaxel Gemcitabine Pemetrexed Prior PD - (L)1 No Prior PD - (L)1 PD - (L)
Slide 22: A Precision Approach to KRAS-G12V Driven NSCLC
22 PROPERTY OF VERASTEM INC. A Precision Approach to KRAS - G12V Driven NSCLC VS - 6766 Inhibits CRAF Source: Ishii et al. Cancer Res (2013), Blasco, R. B. et al. Cancer Cell (2011), Lito, P. et al. Cancer Cell (2014), Sanclemente, M. et al. Cancer Cell (2018) CRAF, but not BRAF, ablation improves s
Slide 23: FRAME: Focusing on Advanced Non-Small Cell Lung Cancer
23 PROPERTY OF VERASTEM INC. Advanced Solid Cancers VS - 6766 (V) oral twice wkly x 3 wks every 4 wks Defactinib (D) oral BID daily x 3 wks q 4 wks 3 cohorts with increasing doses explored Phase I FRAME 1 : Focusing on Advanced Non - Small Cell Lung Cancer *Refractory to conventional treatment or fo
Slide 24: Evidence of Durable Activity Across KRASm Refractory NSCLC
24 PROPERTY OF VERASTEM INC. -50 -40 -30 -20 -10 0 10 20 30 40 Best Response (% Change from Baseline) * 0 12 24 36 48 FRA101017 FRA102005 FRA101018 FRA101020 FRA102004 FRA101010 FRA102009 FRA102008 FRA102007 FRA102006 FRA102002 Time on Treatment (Weeks) * Combination of VS - 6766 (2x/wk) + Defactini
Slide 25: Monotherapy Active in Refractory KRAS Mutant NSCLC Adenocarcinoma
25 PROPERTY OF VERASTEM INC. 0 10 20 30 40 PFS (Weeks) KRAS mut NSCLC 24 55 65 120 140 Monotherapy VS - 6766 VS - 6766 Monotherapy Active in Refractory KRAS Mutant NSCLC Adenocarcinoma G12o = G12D, R or S Best Response by RECIST v1.1 Progression Free Survival ASCO 2017, presented by: Maxime Chénard
Slide 26: Confirmed 57% ORR in KRAS G12V NSCLC in Integrated Analysis
26 PROPERTY OF VERASTEM INC. Preclinical evidence suggests combination with Defactinib may improve efficacy in KRAS G12V Activity of VS - 6766 as a single agent and in combo with Defactinib in KRAS G12V 1 additional confirmed PR in KRAS G12V mutant patient as of Mar - 2020 VS - 6766 ± Defactinib Has
Slide 27: NSCLC Clinical Strategy: KRAS Mutant, Enriched G12V, Phase 2
27 PROPERTY OF VERASTEM INC. NSCLC Clinical Strategy: KRAS Mutant (mt), enriched G12V, Phase 2, Recurrent NSCLC for Potential Accelerated Approval Defactinib+VS - 6766 1 KRAS mt G12V N=16 Expansion Phase • Recurrent NSCLC • 1 - 2 prior regimens • 1 prior platinum - containing chemo; • Prior CPI unle
Slide 28: NSCLC Represents Significant Market Potential: Key Takeaways and Next Steps
28 PROPERTY OF VERASTEM INC. NSCLC Represents Significant Market Potential for VS - 6766 ± Defactinib High unmet need across KRASm lung adenocarcinoma High disease control and time on therapy seen across KRASm in a heavily refractory patient population Strong signal seen in KRAS G12V with VS - 6766
Slide 29: Defactinib High Priority Indications Supported by Initial Data
29 PROPERTY OF VERASTEM INC. VS - 6766 “ Defactinib High Priority Indications Supported by Initial Data LGSOC 1,2 KRAS G12V NSCLC 1,2 Expansion Opportunities Pancreatic 1,2 Endometrial 1 Additional G12V & G12D mt cancers 1 Uveal Melanoma 2 BRAF mt melanoma 1,2 BRAF mt colorectal BRAF mt prostate 2 O
Slide 30: Corporate
Corporate
Slide 31: Key Upcoming Milestones
31 PROPERTY OF VERASTEM INC. Present new preclinical data in combination with KRAS - G12C inhibitors in September 2020 Commence registration - directed clinical trials in LGSOC and KRAS mutant NSCLC by the end of 2020 Submit updated data from the NSCLC cohort of the Phase 1/2 FRAME study to the IASL
Slide 32: Key Financial Statistics
32 PROPERTY OF VERASTEM INC. Key Financial Statistics Cash, cash equivalents & short - term investments as of 6/30/2020 $160.8M Proforma cash after transaction close; prior to any transaction expenses $230M Shares fully diluted as of 6/30/2020 188.2M Hercules Term Loan Facility as of 6/30/2020 $35.0
Slide 33: Experienced Senior Management Team
33 PROPERTY OF VERASTEM INC. Brian Stuglik Chief Executive Officer Cathy Carew Chief People & Organizational Strategy Officer Hagop Youssoufian, MSc, M.D. Head of Medical Strategy Principal – HR Collaborative Ironwood, ActiveBiotics, Dynogen, Tufts Health Plan CMO, BIND Therapeutics, EVP, Progenics,