Verastem, Inc. · NASDAQ:VSTM
Verastem — BTIG KOL Event (December 2020)
35 slides from Verastem's conference presentation, Dec 17, 2020
Slide 1: BTIG KOL Event December 17, 2020
BTIG KOL Event December 17, 2020 NASDAQ: VSTM
Slide 2: On Today's Call
2 PROPERTY OF VERASTEM INC. On Today’s Call *On April 23, 2019, we entered into a 4 th Amendment to our existing Agreement with Hercules Capital, Inc. whereas we may borrow up to an aggregate amount of $75.0 mill io n, of which $35.0 million was outstanding as of the date of amendment and 6/30/2020.
Slide 3: Safe Harbor Statement
3 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 candidates, that are subject
Slide 4: Low-Grade Serous Ovarian Cancer Treatment Landscape and Clinical Perspective
Low - Grade Serous Ovarian Cancer Treatment Landscape and Clinical Perspective Kathleen Moore, MD, MS, Stephenson Cancer Center at the University of Oklahoma
Slide 5: Treatment Landscape and Clinical Perspective: Kathleen Moore, MD, MS
5 PROPERTY OF VERASTEM INC. Treatment Landscape and Clinical Perspective Kathleen Moore, MD, MS, Stephenson Cancer Center at the University of Oklahoma • Dr. Moore is currently an Associate Professor in the Division of Gynecologic Oncology at the University of Oklahoma. She is the Associate Director
Slide 6: What is Low-Grade Serous Ovarian Cancer (LGSOC)?
6 PROPERTY OF VERASTEM INC. What is Low - Grade Serous Ovarian Cancer (LGSOC)? Epithelial cells line the surface of the ovary and LGSOC is a type of epithelial cell cancer, or “carcinoma” Approximately half of those diagnosed are in their 20s, 30s, or 40s and 85% of cases will experience recurrence
Slide 7: LGSOC is a predominantly RAS-driven Subset of Ovarian Cancer
7 PROPERTY OF VERASTEM INC. LGSOC is a predominantly RAS - driven Subset of Ovarian Cancer Variable LGSOC (Grade 1) HGSOC (Grade 2/3) Nuclear atypia Uniform round to oval with little variation +++ Marked variation Mitotic Index <12 mitosis per 10 hpf >12 mitoses per 10 hpf Chromatin and variation in
Slide 8: LGSOC is Relatively Chemo-Resistant
8 PROPERTY OF VERASTEM INC. LGSOC is Relatively Chemo - Resistant • NCDB Propensity score - matched, NCDB study of 755 women with advanced LGSOC, Median OS for those receiving platinum/ taxane - based chemo after primary CRS was 88.2 months compared to 95.9 months among those who were observed and d
Slide 9: First-line Treatment of Advanced LGSOC: Utilizing Hormonal Therapy
9 PROPERTY OF VERASTEM INC. First - line Treatment of Advanced LGSOC: Utilizing Hormonal Therapy MD Anderson: 1 ° CRS C/T +/ - HMT ( n=203) • 70 received Hormonal therapy maintenance (HMT) after C/T • Median PFS carbo/ taxol /OBS vs. carbo/ taxol /HMT=26.4 vs. 64.9 mos (p<0.001) • Letrozole most com
Slide 10: Trial design: chemotherapy plus letrozole vs letrozole
Stage Il-IV Primary LGSC of Ovary or Peritoneum; Primary Cytoreductive Surgery Randomization Paclitaxel and carboplatin AUC 5 or 6 x 6 cycles + Letrozole 2.5 mg PO until disease progression or severe toxicity \ Letrozole 2.5 mg PO daily x 6 cycles and ‘| then continued until disease progression or /
Slide 11: Recurrent LGSOC Responds Poorly to Chemotherapy
11 PROPERTY OF VERASTEM INC. Kurman & Shih 2011 ORR SD Number Carboplatin 3 15 25 PLD 0 11 21 Paclitaxel 1 11 18 Carbo/Paclitaxel 0 7 10 Topotecan 0 5 10 Carbo/ Gemcitabine 0 1 1 Percentage 5% 59% N=85 Gershenson et al Gyne Oncol 2009 Recurrent LGSOC Responds Poorly to Chemotherapy MEK inhibitor
Slide 12: Phase II Trial of Selumetinib in Low Grade Serous Ovarian Cancer
12 PROPERTY OF VERASTEM INC. PHASE II TRIAL OF SELUMETINIB - MEK INHIBITOR IN LOW GRADE SEROUS OVARIAN CANCER Farley et al Lancet Oncol 2013
Slide 13: Trametinib GOG 281 Study Design and Eligibility
13 PROPERTY OF VERASTEM INC. Study Design Eligibility Criteria Recurrent LGSOC Prospective digital path review Measurable disease by RECIST 1.1 At least 1 prior platinum regimen Unlimited no. prior therapies No prior MEKi, BRAFi Cannot have received all 5 SOC R Trametinib 2 mg daily continuously unt
Slide 14: Trametinib in LGSOC
14 PROPERTY OF VERASTEM INC. TRAMETINIB IN LGSOC Trametinib Control (SOC) Median (Months) 95% CI 13.0 (9.9 – 15.0) 7.2 (5.6 - 9.9) Hazard Ratio 95% CI 0.48 (0.36 – 0.64 ) One - sided p - value <0.0001 Trametinib Control (SOC) Median (Months) 95% CI 37.0 (30.3 to NE) 29.2 (23.5 to 51.6) Hazard Ratio
Slide 15: Response by RECIST 1.1
15 PROPERTY OF VERASTEM INC. Response by RECIST 1.1 Arm No. Pts CR + PR /Treated Objective Response Rate (95% CI) Stable Disease Rate Response Duration Months (95% CI) Odds Ratio For ORR (95% CI) P - Value Trametinib 34/130 26.2% (19.0 - 34.0) 59.2% 13.6 (8.1 - 18.8) 5.4 (2.4 - 12.2) < 0.0001 Contro
Slide 16: MILO Study Design
16 PROPERTY OF VERASTEM INC. MILO Study Design • Study initiation: June 2013 • Interim analysis cutoff date: January 2016 (N=303)* • Updated analysis cutoff date: January 2019 (N=341) *Study enrollment discontinued after this planned interim PFS analysis crossed the predefined futility boundary (obs
Slide 17: Binimetinib (MILO Trial) versus Physician Choice
17 PROPERTY OF VERASTEM INC. Binimetinib (MILO Trial) versus Physician Choice MILO trial: Standard of care treatment Median Progression - free survival 11.5 months ; Median Overall survival 34 months GOG 281 SOC: median PFS 7.2 months; median OS 29.2 months Grisham et al IGCS, Brazil 2019 BICR 31% o
Slide 18: KRAS Mutation Associated with Prolonged PFS with Binimetinib
18 PROPERTY OF VERASTEM INC. KRAS MUTATION ASSOCIATED WITH PROLONGED PFS IN PATIENTS TREATED WITH BINIMETINIB Median PFS for Binimetinib KRAS Mutant: 17.7 months (12, NA) KRAS WT: 10.8 months (5.5, 16.7) P= 0.006 Median PFS for Phys Choic e KRAS Mutant: 14.6 months (9.4, NA) KRAS WT: 11.5 months (5.
Slide 19: There is a Continued Need for New Therapeutic Options for LGSOC Patients
19 PROPERTY OF VERASTEM INC. Recurrent low grade serous ovarian cancer responds very poorly to chemotherapy Trametinib led to a significant improvement in PFS and is now NCCN listed as an option for recurrent disease Similar results were not seen with binimetinib but the study design differed in ter
Slide 20: Development History of VS-6766
Development History of VS - 6766 Jonathan Pachter, PhD, Chief Scientific Officer, Verastem Oncology
Slide 21: LGSOC VS-6766 + Defactinib Current Data
Low - Grade Serous Ovarian Cancer VS - 6766 + Defactinib Current Data Jonathan Pachter, PhD, Chief Scientific Officer, Verastem Oncology
Slide 22: VS-6766 is a Unique Small Molecule RAF/MEK Inhibitor
22 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;
Slide 23: Favorable Tolerability Profile for Intermittent Dosing Regimen
23 Favorable Tolerability Profile for Novel Intermittent Dosing Regimen of VS - 6766 plus Defactinib Daily at MTD N=6 28 - day cycle 4mg twice weekly N=26 28 - day cycle RP2D (VS - 6766 3.2mg twice weekly + defactinib 200mg twice daily) N=26 21 days of 28 - day cycle Adverse Event Grade ≥3 Grade ≥3
Slide 24: VS-6766 with Defactinib Shows Robust ORR with Durability in Refractory LGSOC
24 VS - 6766 in Combination with Defactinib Shows Robust ORR with Durability in Refractory LGSOC with Expanded Number of Patients (n=17) 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 -70 -60 -50 -40 -30 -20 -10 0 10 20 Response by RECIST Time (months) R e s p o n s e ( % c h a n g e f r o m b a s e l i
Slide 25: VS-6766 with Defactinib Robust ORR at Phase 2 Dose Level
25 VS - 6766 in Combination with Defactinib Shows Robust ORR with Durability in Refractory LGSOC at Phase 2 Dose Level • ORR in KRAS mt = 50% (3/6); data still maturing • Current overall ORR = 45% (5/11); data still maturing • 9/11 (82%) still on study at RP2D 1 • 2 pts on treatment for 2.5 yrs 0 2
Slide 26: Registration-Directed Phase 2 in Recurrent LGSOC: Adaptive Design
26 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 FDA Was Supportive of Development Strategy and Adaptive Design This Reg
Slide 27: Question & Answer Session with Dr. Kathleen Moore
www.verastem.com Question & Answer Session Hosted by Bert Hazlett Featuring Dr. Kathleen Moore
Slide 28: Next Steps Beyond LGSOC
Next Steps Beyond LGSOC Brian Stuglik, Chief Executive Officer, Verastem Oncology Jonathan Pachter , PhD, Chief Scientific Officer, Verastem Oncology
Slide 29: High Unmet Needs in RAS/RAF/MEK/ERK-Driven Cancers
29 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 30: VS-6766 ± Defactinib Has Confirmed 57% ORR in KRAS G12V NSCLC
30 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 31: NSCLC Clinical Strategy: KRAS G12V Phase 2
31 PROPERTY OF VERASTEM INC. NSCLC Clinical Strategy: KRAS Mutant (mt), Enriched G12V, Phase 2, Recurrent NSCLC for Potential Accelerated Approval 1 Defactinib 200 mg PO BID (21/28 days) + VS - 6766 3.2 mg PO 2x/wk (21/28 days) 2 VS - 6766 4.0 mg PO 2x/wk (21/28 days) This Registration - directed Ph
Slide 32: Vertical Blockade: VS-6766 as Backbone of Therapy
32 PROPERTY OF VERASTEM INC. ▪ Current Challenges o Blocking any single target in the pathway is insufficient for maximum depth and duration of anti - tumor efficacy • e.g. SHP2i, KRAS - G12Ci, RAFi , MEKi , ERKi o Vertical inhibition concept is now well established • Necessary to block more than 1
Slide 33: Parallel Pathway Blockade: VS-6766 as Backbone of Therapy
33 PROPERTY OF VERASTEM INC. ▪ Current Challenges o Blocking Ras pathway can be circumvented through parallel pathways • e.g. PI3K/AKT/mTOR, FAK, RhoA , YAP o Combinations of MEKi + AKTi have shown poor tolerability ▪ Solutions offered with VS - 6766 o Good tolerability with twice weekly VS - 6766 o
Slide 34: High Priority Indications Supported by Initial Data
34 VS - 6766 “ Defactinib High Priority Indications Supported by Initial Data Registration - Directed Trials Initiating in 4Q20 LGSOC 1,2 KRAS G12V NSCLC 1,2 Expansion Opportunities Pancreatic 1,2 (10 pt cohort initiated) KRAS mt endometrial 1 (10 pts initiated) Uveal Melanoma 2 (IST initiating) BRA
Slide 35: Question & Answer Session with Verastem Management
www.verastem.com Question & Answer Session Hosted by Bert Hazlett Featuring Verastem Management