Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (May 2021)
48 slides from Verastem's investor presentation, May 26, 2021
Slide 1: Corporate Presentation May 2021
Corporate Presentation May 2021 NASDAQ: VSTM
Slide 2: Safe Harbor Statement
2 This presentation includes forward-looking statements about, among other things, Verastem Oncology’s programs and product candidates, including anticipated regulatory submissions, approvals, performance and potential benefits of Verastem Oncology’s product candidates, that are subject to substanti
Slide 3: Well Positioned to Capitalize on Growth Opportunities
3 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 RAS mutant cancers 30% of all human cancers are driven by mutations in RAS family of genes; VS-6766 combi
Slide 4: Verastem Oncology Strategic Transformation
4 Verastem Oncology Strategic Transformation November 2020: Initiated registration-directed ph. 2 study in LGSOC September 2020: Divested global rights to Copiktra to Secura Bio February 2020: PIPE financing based on data for new clinical program January 2020: In-licensed global rights to VS-6766, b
Slide 5: VS-6766 RAF/MEK Inhibitor Program Overview
VS-6766 RAF/MEK Inhibitor Program Overview
Slide 6: VS-6766 is a differentiated, best-in-class asset
6 Unique dual RAF/MEK targeting mechanism of action Best-in-class safety & tolerability profile relative to marketed MEK inhibitors, with potential for combinability with agents from multiple target classes Novel intermittent dosing schedule; convenient oral regimen Clear signals of clinical
Slide 7: VS-6766 High Priority Registration Indications
7 VS-6766 High Priority Registration Indications Registration-Directed Trials Initiated in 4Q20 LGSOC1,2 KRASG12V NSCLC1,2 Additional Indication Opportunities Pancreatic1,2 (10 pt cohort initiated) KRAS mt endometrioid1 (10 pts initiated) Uveal Melanoma2 (IST initiated) Melanoma1,2 Col
Slide 8: Robust Pipeline Targeting the RAS Pathway
8 Robust Pipeline Targeting the RAS Pathway and Multiple Growth Opportunities RAMP 201 study = NCT04625270 RAMP 202 study = NCT04620330 FRAME study = NCT03875820 *Pre-clinical studies ongoing in multiple KRAS mutant tumors FDA Breakthrough Therapy Designation for VS-6766 + defactinib
Slide 9: VS-6766 is a Unique Small Molecule RAF/MEK Inhibitor
9 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; Lito et al., Cancer Cell, 2014;
Slide 10: Vertical Blockade: VS-6766 as backbone of therapy
10 ▪ 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 target in the pathway o Many o
Slide 11: Parallel Pathway Blockade: VS-6766 as backbone of therapy
11 ▪ 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 opens up intermittent dosing opt
Slide 12: VS-6766 +/- Defactinib in Low-Grade Serous Ovarian Cancer
VS-6766 +/- Defactinib in Low-Grade Serous Ovarian Cancer
Slide 13: Favorable Tolerability Profile with Novel Intermittent Dosing Regimen
13 Favorable Tolerability Profile with Novel Intermittent Dosing Regimen VS-6766 monotherapy Daily at MTD N=6 28-day cycle RP2D VS-6766 monotherapy 4mg twice weekly N=26 28-day cycle RP2D (VS-6766 3.2mg twice weekly + defactinib 200mg twice daily) N=38 21 days of 28-day cycle Treatment Related Adver
Slide 14: Treatment Related Adverse Events Details
14 Treatment Related Adverse Events Details* (≥10% patients in cohort 3.2mg 6766 and Def 200mg) VS-6766 4mg Twice Weekly (4 wks of every 4 wks)1 n=22 VS-6766 3.2mg Twice Weekly Def 200mg BID (3 wks of every 4 wks)2 n=38 Gr1/2 Gr3/4 Gr1/2 Gr3/4 Rash 15 5 32 2 CK Elevation 13 2 19 2 AST Elevation 1 13
Slide 15: Robust ORR with Durability in Refractory LGSOC
15 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 n
Slide 16: Updated Dec. 2020 read-out: ORR continues to strengthen
16 In an updated Dec. 2020 read-out (n=24), ORR data has continued to strengthen, in both KRAS mt and KRAS wt patients, with a consistent safety profile Overall response rate (ORR) is 52% (11 of 21 response evaluable patients) ▪ KRAS mutant ORR at 70% (7 of 10 response evaluable patients) ▪ KRAS w
Slide 17: LGSOC: Limited Treatment Options with High Unmet Need
17 31-35% discontinuation rate with MEK inhibitors due to AEs Few discontinuations in the FRAME study due to AEs Low-Grade Ovarian Cancer – Treatment Algorithm1 Observe only Pt Chemo Combo: Carbo-Pt + Paclitaxel (preferred) + Beva for Stage II-IV (incl maintenance Beva) OR Hormonal Tx (2B) Pt-
Slide 18: KRAS wt patients represent 70% of LGSOC population
18 KRAS wt patients represent 70% of the LGSOC patient population LGSOC is a type of ovarian cancer that disproportionately affects younger women Patients often experience significant pain and suffering from their disease over time A slow growing cancer, that has a median survival of almost 10 years
Slide 19: RAMP 201: Phase 2 Recurrent LGSOC Adaptive Design
19 RAMP 201: KRAS Mutated (mt) and Wild Type (wt), Phase 2, Recurrent LGSOC Adaptive Design for Potential Accelerated Approval *Dosing: Defactinib + VS-6766 combo: Defactinib 200mg PO BID: 21/28 days + VS-6766 3.2mg PO 2x/wk 21/28 days; VS-6766 monotherapy: VS6766 4.0 mg PO 2x/wk 21/28 days **Expans
Slide 20: Patient-months of Therapy Per Year
20 NSCLC KRAS G12C3 Pancreatic3 LGSOC3 Endometrioid3 Metastatic uveal melanoma3 ~4k ~2k wild type kras mutation ~6K patients US1 ~80K patients WW1 Patient-months of Therapy Per Year2 (across all 2L+ patients) 1 Source: Monk, Randall, Grisham, The Evolving Landscape of Chemotherapy in Newly Diagnosed
Slide 21: VS-6766 +/- Defactinib in NSCLC
VS-6766 +/- Defactinib in NSCLC
Slide 22: High Unmet Need in Refractory KRASm NSCLC Adenocarcinoma
22 0 5 10 15 G12C G12V G12D G12A G13C G12S G13D % of Patients KRAS Mutation Advanced or Metastatic NSCL Cancer Recommend Histologic and Molecular Subtyping5 Appropriate targeted agent Chemotherapy Docetaxel Gemcitabine Pemetrexed Prior PD-(L)1 No Prior PD-(L)1 PD-(L)1 Chemo PD-(L)1 PD-(L)1 s
Slide 23: A Precision Approach to KRAS-G12V Driven NSCLC
23 A Precision Approach to KRAS-G12V Driven NSCLC VS-6766 Inhibits CRAF - The key driver of KRAS-G12V mutant NSCLC 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, ablati
Slide 24: VS-6766 +/- FAKi induces tumor regression in KRAS G12V NSCLC in vivo
24 VS-6766 +/- FAKi induces significant tumor regression in KRAS G12V mt NSCLC in vivo model, with clear differentiation from trametinib Doses Tested Trametinib: 0.1 mg/kg QD (5 days/week) VS-6766: 0.1 mg/kg QD (5 days/week) FAKi: 50 mg/kg BID (5 days/week) KRAS G12V mutant; Trp53 KO NSCLC • VS-6766
Slide 25: Case Study: Response in a patient with KRAS G12V mutant NSCLC
25 Case Study: Response to VS-6766 + defactinib in a patient with KRAS G12V mutant NSCLC Source: Krebs et al. AACR 2021 May 2019: Diagnosed with NSCLC June 2019 - Sept 2019: Treated with first line Carboplatin + Pemetrexed + Pembrolizumab Oct 2019: Progression, palliative RT to right hip Nov 2019 –
Slide 26: 57% ORR in KRASG12V NSCLC in Integrated Analysis
26 Preclinical evidence suggests combination with Defactinib may improve efficacy in KRASG12V Activity of VS-6766 as a single agent and in combo with Defactinib in KRASG12V VS-6766 ± Defactinib Has a Confirmed 57% ORR in KRASG12V NSCLC in Integrated Analysis Strong Signal Identified in KRASG12V
Slide 27: NSCLC Clinical Strategy: Registration-directed Phase 2
27 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 Phase 2 Study commenced December 2
Slide 28: Future Opportunities: VS-6766 as Backbone of RAS Therapy
Future Opportunities: VS-6766 as Backbone of RAS Therapy
Slide 29: Vertical Blockade: Preclinical synergy with several targets
29 29 H 2 1 2 2 S W 8 3 7 H 1 3 7 3 S W 1 5 7 3 H 3 5 8 H 2 0 3 0 M I A P A C A 2 0 10 20 30 40 50 VS-6766 + AMG 510 C o m b i n e d S y n e r g y S c o r e NSCLC Panc Synergy Antagonism Indication CRC Vertical Blockade: Preclinical synergy in combination with several promising targets H 2 1 2 2 H 1
Slide 30: Synergy of VS-6766 + G12C inhibitor AMG 510
30 30 Synergy of VS-6766 + G12C inhibitor AMG 510 across G12C mutant NSCLC, CRC & Pancreatic cancer cell lines Doses Tested Trametinib: 0.3 mg/kg QD VS-6766: 0.3 mg/kg QD FAKi: 50 mg/kg BID AMG 510: 30 mg/kg QD -100 0 100 200 300 400 Response at Day 10 R e s p o n s e ( % c h a n g e f r o m b a s e
Slide 31: Parallel Pathway Blockade: Two synergistic combinations in clinic
31 31 S W 1 5 7 3 H 1 3 7 3 H 3 5 8 M I A P A C A 2 H 2 1 2 2 A 4 2 7 S K L U 1 H P A F I I A S P C 1 H P A C H 2 2 9 1 H 2 4 4 4 C A P A N 2 H 4 4 1 P A N C 0 3 2 7 C F P A C 1 -40 -20 0 20 40 VS-6766 + M2698 C o m b i n e d S y n e r g y S c o r e NSCLC Panc Synergy Antagonism 80% (4/5) 66% (4/6)
Slide 32: Key VSTM Milestones 2020-2022
32 Key VSTM Milestones 2020-2022 LGSOC NSCLC Corporate 1H2020 2H2020 1H2021 2H2021 1H2022 VS-6766 In- Licensed from Chugai Copiktra divested to Secura Bio RAMP-201 Amended to Include KRAS wt patients in Selection Phase RAMP-201 Study Initiated RAMP-202 Study Initiated RAMP-201 Top-Line Data from Sel
Slide 33: Corporate
Corporate
Slide 34: Key Financial Statistics
34 Key Financial Statistics Cash, cash equivalents & investments as of 3/31/2021 $127.1M Shares fully diluted as of 3/31/2021 195.8M 5.00% Convertible Senior Notes Due 2048 (2018 Notes) as of 3/31/2021 $0.3M* 5.00% Convertible Senior Notes Due 2048 (2020 Notes) as of 3/31/2021 $28.0M** Insider owner
Slide 35: Backup Slides
Backup Slides www.verastem.com
Slide 36: High Unmet Needs in RAS/RAF/MEK/ERK-Driven Cancers
36 NSCLC Incidence3,5: 194K Colorectal Incidence5: 105K Pancreatic Incidence5: 58K Uterine Endometrioid Incidence4,5: 59K Melanoma Incidence5: 108K Multiple Myeloma Incidence5: 32K Melanoma Incidence5: 108K Ovarian Incidence5: 22K Papillary Thyroid Incidence5,6: 42K Ovarian Incidence5: 22K High Unme
Slide 37: KRAS G12V and G12D Represent ~50% of KRAS Mutations
37 37 KRAS G12V and G12D Represent ~50% of KRAS Mutations across Human Cancers 21.40% G12V 25.30% G12D 5.10% G12A 13.30% G12C 2.70% Q61H 32.20% Others Pancreatic Adenocarcinoma1 G12D G12V G12R Q61H Q61R G12A G12C 0 10 20 30 Pancreatic Cancer KRAS Mutation % o f p a t i e n t s Uterine Endometrioid C
Slide 38: VS-6766 and FAK inhibitor combination more robust in vivo
38 38 VS-6766 and FAK inhibitor combination leads to more robust anti-tumor efficacy in vivo Ovarian cancer model (TOV-21g KRAS(G13C) mutant) NSCLC cancer model (H2122 KRAS(G12C) mutant) J. Paradis, AACR 2020 0 5 10 15 0 200 400 600 Tumor growth Days on treatment T u m o r v o l u m e ( m m 3 + / -
Slide 39: Overcoming Key Resistance Mechanisms to MEK Inhibitors
39 39 Overcoming Key Resistance Mechanisms to MEK Inhibitors ▪ MEK inhibition induces compensatory activation of pFAK preclinically and clinically Pre dose Post VS-6766 Post com bination 0 50 100 150 p-FAK H - S c o r e o Trametinib induced ↑ pFAK (Y397) preclinically in KRAS mt NSCLC cell lines o A
Slide 40: Pharmacokinetic Profiles of VS-6766 + Defactinib
40 40 Pharmacokinetic Profiles of VS-6766 + Defactinib in Combination Similar to that seen in Single Agent Studies Cohort Dose (mg) N Subject AUC0-24h (h*ng/mL) Cmax (ng/mL) 1 3.2 (with 200mg VS) 3 Mean 6179 354 CV% 32.1 30.4 2a 4 (with 200mg VS) 5 Mean 5353 289 CV% 15.8 16.0 2b 3.2 (with 400mg VS)
Slide 41: Robust ORR with Durability in LGSOC at Phase 2 Dose Level
41 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 RP2D1 • 2 pts on treatment for 2.5 yrs 0 2 4 6
Slide 42: Status: Combination of VS-6766 with Everolimus
42 Synergy of VS-6766 + everolimus observed broadly across cancer cell lines with various KRAS mutation variants A well-tolerated RP2D for VS-6766 + everolimus has been established with intermittent dosing of both agents (twice weekly; 3 wks on/1 wk off) KRAS mutant NSCLC expansion cohort is c
Slide 43: VS-6766 upregulates MHC Class I antigens on tumor cells
43 43 VS-6766 upregulates MHC Class I antigens on tumor cells: a mechanism for potentiation of I/O efficacy Cell Line Tumor type RAS/RAF mutation status A549 Lung KRASmut G12S TOV21g Ovarian KRASmut G13C SKMEL5 Melanoma BRAFmut V600E IGR-1 Melanoma BRAFmut V600E WM115 Melanoma BRAFmut V600E A549 TOV
Slide 44: VS-6766 enhances tumor growth inhibition with anti-PD-1
44 44 VS-6766 enhances tumor growth inhibition when combined with anti-PD-1 in the CT26 KRAS (G12D) syngeneic model -100 0 100 200 300 400 Response at Day 13 % C h a n g e i n T u m o r V o l u m e Vehicle VS-6766 anti-PD-1 VS-6766 + anti-PD-1 20 40 60 80 100 0 20 40 60 80 100 Survival Time P e r c
Slide 45: LGSOC Market Opportunity – Reference Calculations
45 NSCLC KRAS G12C3 Pancreatic3 LGSOC1 Endometrioid3 Metastatic uveal melanoma3 LGSOC Market Opportunity – Reference Calculations Patient-months of Therapy Per Year (across all 2L+ patients)2 Average months on Therapy (per patient)2 Number of Patients (2L+)2 - 10,000 20,000 30,000 40,000 1 Prevalenc
Slide 46: Breakthrough Therapy Designation benefits
46 46 A drug with a Breakthrough designation will have… ▪ Increased communication with FDA during drug development and review ▪ FDA guidance to ensure that the design of clinical trials are as efficient as practicable ▪ A cross-disciplinary project lead assigned to the FDA review team and increased
Slide 47: Strong Patent Protection
47 47 Strong Patent Protection ▪ COM for VS-6766 to 2027 & defactinib to 2028, Hatch Waxman should extend to 2032 ▪ VS-6766 intermittent dosing regimen until 2038 if granted ▪ FAK/MEK combination to 2035 ▪ VS-6766/defactinib combination until 2040 if granted ▪ Method of manufacture for VS-6766 to 20
Slide 48: Experienced Senior Management Team
48 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, CMO & EVP, Ziopha