Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (February 2021)
40 slides from Verastem's investor presentation, Feb 25, 2021
Slide 1: Corporate Presentation February 2021
Corporate Presentation February 2021 NASDAQ: VSTM
Slide 2: Safe Harbor Statement
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 potential benefits of Verastem Oncology products and product candidates
Slide 3: Well Positioned to Capitalize on Growth Opportunities
Well Positioned to Capitalize on Growth Opportunities We are a biopharmaceutical company committed to developing and commercializing new medicines for patients battling cancer New lead clinical program has best-in-class potential Rapid development paths to market Significant downstream market opport
Slide 4: 2020 Highlights: A Transformative Year for Verastem Oncology
2020 Highlights: A Transformative Year for Verastem Oncology January:In-licensed global rights to VS-6766, best-in-class RAF/MEK inhibitor, from Chugai February: PIPE financing based on data for new clinical program September:Divested global rights to Copiktra to Secura Bio November:Initiated regist
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
VS-6766 is a differentiated, best-in-class asset potentially applicable across multiple patient populations 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 ta
Slide 7: VS-6766 is a Unique Small Molecule RAF/MEK Inhibitor
VS-6766 is a Unique Small Molecule RAF/MEK Inhibitor Growth factors RTK RAS VS-6766 inhibits both MEK & RAF kinase activities MEK inhibitors paradoxically induce MEK phosphorylation (pMEK) by relieving ERK-dependent feedback inhibition of RAF RAF MEK ERK Tumor Growth By inhibiting RAF phosphorylatio
Slide 8: Vertical Blockade: VS-6766 as backbone of therapy for RAS pathway-driven tumors
Vertical Blockade: Establishing VS-6766 as the backbone of therapy for RAS pathway-driven tumors EGFRi FGFRi Growth factors RTK 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, E
Slide 9: Parallel Pathway Blockade: VS-6766 as backbone of therapy
Parallel Pathway Blockade: Establishing VS-6766 as the backbone of therapy for RAS pathway-driven tumors EGFRi FGFRi Growth factors RTK Extracellular Matrix Integrin α β Current Challenges o Blocking Ras pathway can be circumvented through parallel pathways e.g. PI3K/AKT/mTOR, FAK, RhoA, YAP SHP2i S
Slide 10: Robust Pipeline Targeting the RAS Pathway and Multiple Growth Opportunities
Robust Pipeline Targeting the RAS Pathway and Multiple Growth Opportunities VS-6766 (RAF/MEK inhibition) Combinations FRAME study in advanced LGSOC1,2 with defactinib FRAME study in advanced KRAS mt NSCLC1,2 with defactinib FRAME study in advanced CRC1,2 with defactinib FRAME study in advanced KRAS-
Slide 11: VS-6766 +/- Defactinib in Low-Grade Serous Ovarian Cancer
VS-6766 +/-Defactinib in Low-Grade Serous Ovarian Cancer
Slide 12: What is Low-Grade Serous Ovarian Cancer (LGSOC)?
What is Low-Grade Serous Ovarian Cancer (LGSOC)? LGSOC is a type of ovarian cancer that disproportionately affects younger women ~30% of LGSOC Patients Have KRAS mt ~70% of LGSOC Shows RAS Pathway-Associated mts 1,000 to 2,000 patients in the U.S. and 15,000 to 30,000 worldwide diagnosed with LGSOC
Slide 13: LGSOC: Limited Treatment Options With High Unmet Need
LGSOC: Limited Treatment Options With High Unmet Need Low-Grade Ovarian Cancer – Treatment Algorithm1 Limited Response Rates for Available Treatments: Stage IA-IB Observe only Stage ICStage II-IV Pt Chemo Combo: Carbo-Pt + Paclitaxel (preferred) + Beva for Stage II-IV (incl maintenance Beva) OR Horm
Slide 14: Favorable Tolerability Profile with Novel Intermittent Dosing Regimen
Favorable Tolerability Profile with Novel Intermittent Dosing Regimen Summary of Adverse Events Grade ≥3 Occurring in ≥ 5% of patients 1 Chenard-Poirier, et al. ASCO 2017 References: Banerji, Q4 2020 report; Data on file RP2D: recommended phase 2 dosing 14
Slide 15: VS-6766 3.2 mg + Defactinib 200 mg Selected as RP2D
VS-6766 3.2 mg + Defactinib 200 mg Selected as RP2D Treatment Related Adverse Events Occurring in ≥ 10 Patients (Total) Q4 2020 Update Treatment Related Adverse Events Details* (≥10% patients in cohort 3.2mg 6766 and Def 200mg) VS-6766 3.2mg Def 400mg Cohort 2b n=3 VS-6766 4mg Def 200mg Cohort 2a n=
Slide 16: VS-6766 with Defactinib Shows Robust ORR with Durability in Refractory LGSOC
VS-6766 in Combination with Defactinib Shows Robust ORR with Durability in Refractory LGSOC with Expanded Number of Patients (n=17) Response by RECIST 20 Response (% change from baseline) 0 Time on Treatment G12D G12D G12A G12V -10 -20 -30 -40 -50 -60 -70 G12D * # WT * WT * Undocumented *D33E, I24N
Slide 17: Phase 2 Recurrent LGSOC Adaptive Design
KRAS Mutated (mt) and Wild Type (wt), Phase 2, Recurrent LGSOC Adaptive Design for Potential Accelerated Approval Selection Phase*Expansion Phase** Recurrent LGSOC Measurable disease (RECIST 1.1) Prior MEKi allowed Approximately 32 subjects Defactinib+VS-6766 Defactinib 200 mg PO BID 21/28 days + VS
Slide 18: VS-6766 +/- Defactinib in NSCLC
VS-6766 +/-Defactinib in NSCLC
Slide 19: High Unmet Need in Refractory KRASm NSCLC
High Unmet Need in Refractory KRASm NSCLC Adenocarcinoma NSCLC Adenocarcinoma3 Advanced or Metastatic NSCL Cancer Recommend Histologic and Molecular Subtyping5 15 % of Patients 10 EGFR/ALK/ROS1/B RAF (targeted) Appropriate targeted agent Non-targeted PD-(L)1 1% PD-(L)1 single agent or PD-(L)1 + chem
Slide 20: VS-6766 Inhibits CRAF - Key driver of KRAS-G12V mutant NSCLC
VS-6766 Inhibits CRAF - The key driver of KRAS-G12V mutant NSCLC A Precision Approach to KRAS-G12V Driven NSCLC KRASG12V CRAF Drives KRASG12V NSCLC1,3 CRAF KO vs. WT +83% OS MEK/ERKAKT/mTOR Tumor Growth BRAF KO vs. WT KRASG12V signals mainly through RAF/MEK in contrast to other variants, such as KRA
Slide 21: Strong Signal Identified in KRASG12V to Be Further Validated
Strong Signal Identified in KRASG12V to Be Further Validated VS-6766 ± Defactinib Has a Confirmed 57% ORR in KRASG12V NSCLC in Integrated Analysis Best Response by RECIST in KRASG12V NSCLCTime on Treatment for KRASG12V NSCLC Best Response (% Change from Baseline) 0% -10% -20% -30% -40% -50% -60% -70
Slide 22: NSCLC Clinical Strategy: KRAS Mutant, Enriched G12V, Phase 2
NSCLC Clinical Strategy:KRAS Mutant (mt), Enriched G12V, Phase 2, Recurrent NSCLC for Potential Accelerated Approval Selection PhaseExpansion Phase Recurrent NSCLC 1-2 prior regimens 1 prior platinum-containing chemo; Prior CPI unless contraindicated Measurable disease (RECIST 1.1) Appropriate appro
Slide 23: Future Opportunities: VS-6766 as Backbone of RAS Therapy
Future Opportunities: VS-6766 as Backbone of RAS Therapy
Slide 24: Vertical Blockade: Preclinical synergy with several promising targets
Vertical Blockade:Preclinical synergy in combination with several promising targets VS-6766 + pan-HERi (Afatinib) VS-6766 + SHP2i (RMC-4550) VS-6766 + SOS1i (BI-3406) VS-6766 + Afatinib Combined Synergy Score VS-6766 + BI-3406 100% (6/6) Combined Synergy Score 60% (3/5) 83% (5/6) 20 0 H2122 H1373 MI
Slide 25: Preclinical synergy of VS-6766 + G12C inhibitors in KRAS G12C models
Preclinical synergy of VS-6766 + G12C inhibitors in KRAS G12C mt models Synergy of VS-6766 + G12C inhibitor AMG 510 across G12C mutant NSCLC, CRC & Pancreatic cancer cell lines VS-6766 & FAKi potentiate AMG 510 efficacy in KRAS G12C mutant NSCLC in vivo; Tumor regression in all mice with triple comb
Slide 26: Parallel Pathway Blockade: Two synergistic combinations in clinic
Parallel Pathway Blockade: Two synergistic combinations already progressed to clinical stage VS-6766 + p70S6K/AKTi (M2698) VS-6766 + mTORi (Everolimus) Combined Synergy Score 20 0 -20 SW1573 H1373 H358 MIAPACA2 H2122 A427 SKLU1 HPAFII ASPC1 HPAC H2291 H2444 CAPAN2 H441 PANC0327 CFPAC1 Indication VS-
Slide 27: High Priority Lead Indications with Multiple Growth Opportunities
High Priority Lead Indications with Multiple Growth Opportunities High Priority Indications Supported by Initial Data Expansion Opportunities Pancreatic1,2 (10 pt cohort initiated) 1 Registration-Directed Trials Initiating in 4Q20 KRAS mt endometrial (10 pts initiated) LGSOC1,2 KRASG12V NSCLC1,2 Oth
Slide 28: Corporate
Corporate
Slide 29: Key Financial Statistics
Key Financial Statistics As of September 30, 2020 Revised to include Hercules Debt Repayment
Slide 30: Backup Slides
BackupSlides www.verastem.com
Slide 31: High Unmet Needs in RAS/RAF/MEK/ERK-Driven Cancers
High Unmet Needs in RAS/RAF/MEK/ERK-Driven Cancers KRAS-mutant Cancers1 NSCLC Incidence3,5: 194K 31% Pancreatic Incidence5: 58K 98% Uterine Endometrioid Incidence4,5: 59K 21% Colorectal Incidence5: 105K 45% Ovarian Incidence5:5% 22K NRAS-mutant Cancers1 Melanoma Incidence5: 108K 28% Multiple Myeloma
Slide 32: KRAS G12V and G12D Represent ~50% of KRAS Mutations
KRAS G12V and G12D Represent ~50% of KRAS Mutations across Human Cancers32 % frequency in a total of 780 cancer patients with KRAS mutations1 Pancreatic Adenocarcinoma1 30 % of patients 20 10 21.40% G12V 25.30% G12D 5.10% G12A 13.30% G12C 2.70% Q61H 32.20% Others 0 KRAS Mutation Uterine Endometrioid
Slide 33: VS-6766 and FAK inhibitor combination leads to more robust anti-tumor efficacy in vivo
VS-6766 and FAK inhibitor combination leads to more robust anti-tumor efficacy in vivo QD QD NSCLC cancer model (H2122 KRAS(G12C) mutant) Uveal melanoma model (92.1 GNAQ mutant) 500 400 300 200 100 0 Vehicle Trametinib 1.5 mg/kg QD FAKi 50 mg/kg BID VS-6766 1.5 mg/kg QD VS-6766 + FAKi 600 Tumor volu
Slide 34: Overcoming Key Resistance Mechanisms to MEK Inhibitors
Overcoming Key Resistance Mechanisms to MEK Inhibitors 34 p-FAK 150 H-Score 50 0 MEK inhibition induces compensatory activation of pFAK preclinically and clinically o Trametinib induced ↑ pFAK (Y397) preclinically in KRAS mt NSCLC cell lines o Also observed in patients VS-6766 induced ↑ pFAK (Y397)
Slide 35: Pharmacokinetic Profiles of VS-6766 + Defactinib in Combination
Pharmacokinetic Profiles of VS-6766 + Defactinib in Combination Similar to that seen in Single Agent Studies 35 VS-6766 Cohort Dose (mg) N Subject AUClast (h*ng/mL) Cmax (ng/mL) 1 200 (with 3.2mg RO) 3 Mean 2071 273 CV% 103 80 2a 200 (with 4mg RO) 5 Mean 2252 318 CV% 124 117 2b 400 (with 3.2mg RO) 3
Slide 36: VS-6766 with Defactinib Shows Robust ORR in Refractory LGSOC at Phase 2 Dose
VS-6766 in Combination with Defactinib Shows Robust ORR with Durability in Refractory LGSOC at Phase 2 Dose Level All patients on RP2D:3.2 mg VS-6766 (2x/wk) + 200 mg Defactinib (BID) q3/4 wks Response by RECIST 20 10 FRA101002 Time on Treatment * G12A FRA101001 0FRA101025 * # WT G12V -10 FRA101024
Slide 37: Status: Combination of VS-6766 with Everolimus
Status: Combination of VS-6766 with Everolimus (mTOR inhibitor) 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 w
Slide 38: VS-6766 upregulates MHC Class I antigens on tumor cells
VS-6766 upregulates MHC Class I antigens on tumor cells: a mechanism for potentiation of I/O efficacy 6 Relative mRNA Levels 4 B2M 8 Relative mRNA Levels VS-6766 6 HLA-A 4 2 0 A549TOV21g SKMEL5IGR1WM115 KRAS mtBRAF mt TAP-1 6 Relative mRNA Levels 4 2 0 Relative mRNA Levels 2.0 1.5 Cell Line Tumor ty
Slide 39: Strong Patent Protection for VS-6766 ± Defactinib
Strong Patent Protection for VS-6766 ± Defactinib 39 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 V
Slide 40: Experienced Senior Management Team
Experienced Senior Management Team Brian Stuglik Chief Executive Officer Global VP & Chief Marketing Officer – Lilly Oncology Founding Member – Proventus Health Solutions Daniel Paterson President and Chief Operating Officer CEO – The DNA Repair Co. (now On-Q-ity) PharMetrics (now IMS), Axion Rob Ga