Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (November 2023)
50 slides from Verastem's investor presentation, November 2023
Slide 1: Corporate Presentation
Corporate Presentation November 2023
Slide 2: Disclaimers
Disclaimers 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, as well as Verastem
Slide 3: Well Positioned to Capitalize on Growth Opportunities
Verastem Oncology Well Positioned to Capitalize on Growth Opportunities Lead clinical program has Avutometinib (VS-6766; RAF/MEK clamp) and defactinib (FAK best-in-class potential inhibitor) are clinically active against RAS pathway-driven cancers FDA Breakthrough Therapy Designation; Updated data f
Slide 4: Key VSTM Achievements & Anticipated Milestones
Key VSTM Achievements & Anticipated Milestones 2H2022 1H2023 3Q2023 4Q2023 1Q2024 RAMP 201 Complete RAMP 201 Second target enrollment of Interim Update Expansion Phase Discuss confirmatory trial study design with Initiate confirmatory LGSOC RAMP 201 FDA Launch LGSOC FDA for recurrent LGSOC prog
Slide 5: Avutometinib RAF/MEK Clamp Program Overview
Avutometinib RAF/MEK Clamp Program Overview
Slide 6: Avutometinib is a Differentiated Agent with Potential to Serve as Backbone
Avutometinib is a Differentiated Agent with the Potential to Serve as the Backbone for Combinations Across RAS Pathway-Driven Cancers • Unique RAF/MEK clamp mechanism of action • Novel intermittent dosing schedule; convenient oral regimen • Breakthrough Therapy Designation for combination of avutome
Slide 7: Avutometinib is a Unique Small Molecule RAF/MEK Clamp
Avutometinib is a Unique Small Molecule RAF/MEK Clamp Contrasting Mechanism of Action vs. MEK-Only Inhibitors Growth factors Avutometinib induces dominant negative Avutometinib inhibits both RAF and MEK activities RAF/MEK complexes RTK DMSO Tram Avuto % Inhibition % Inhibition RAS RAF Collaboration
Slide 8: Avutometinib Inhibits Cell Proliferation Across Multiple RAS/MAPK Alterations
Avutometinib Inhibits Cell Proliferation Across Multiple RAS/MAPK Pathway Alterations and Multiple Solid Tumor Histologies MAPK pathway lateration: Indication: KRAS G12C BRAF V600E NSCLC KRAS G12D BRAF class 2 Panc KRAS G12V BRAF class 3 CRC KRAS G12R NRAS mt Melanoma KRAS G12A NF1 mt Endometrial KR
Slide 9: Avutometinib Anti-Tumor Activity in KRAS Mutant Models
Avutometinib (VS-6766) Anti-Tumor Activity in KRAS Mutant Models Superiority vs.Trametinib Collaboration with Mariano Barbacid, CNIO (Spain) Verastem, unpublished data 9
Slide 10: Strong Scientific Rationale for Avutometinib and FAK Inhibitor Combination
Strong Scientific Rationale for Avutometinib and FAK Inhibitor Combination Anti-Tumor Efficacy in KRAS Mutant and Wild-Type LGSOC models Growth factors Extracellular Matrix pFAK KRAS mutant LGSOC PDX model RTK Integrin 150 300 vehicle α Tumor volume (mm3 +/- SEM) β 200 FAKi FAK defactinib avutometin
Slide 11: Optimized Dosing Schedule Defined: Favorable Tolerability Profile
Optimized Dosing Schedule Defined: Favorable Tolerability Profile with Novel Intermittent Dosing Regimen Summary of Adverse Events Grade ≥ 3 Occurring in ≥ 5% of patients Avutometinib monotherapy RP2D RP2D Daily at MTD Avutometinib monotherapy (Avutometinib 3.2mg twice N=6 4mg twice weekly weekly +
Slide 12: RAS Pathway-Driven Cancers and Rational Avutometinib Combinations
RAS Pathway-Driven Cancers and Rational Avutometinib Combinations
Slide 13: Comprehensive approach to establish more complete blockade of RAS pathway
Ongoing comprehensive approach to establish more complete blockade of RAS pathway & resistance pathways Incidence/ Indication Biomarker % Regimen Setting Collaborator Prevalence RAMP201 Prevalence1: 70% Avutometinib + defactinib Relapsed Refractory molecularly profiled LGSOC LGSOC 6K Gynecologic Can
Slide 14: Robust Clinical Program: Avutometinib in multiple combinations
Robust Clinical Program: Avutometinib in multiple combinations across RAS/MAPK pathway-driven tumors CLINICAL STUDY COLLABORATION INDICATION REGIMEN NAME PRECLINICAL PHASE 1 PHASE 2 PHASE 3 WITH LGSOC1 Avutometinib + defactinib RAMP 201 Registration-directed trial: accelerated approval cohort fully
Slide 15: Avutometinib ± Defactinib in Low-Grade Serous Ovarian Cancer
Avutometinib ± Defactinib in Low-Grade Serous Ovarian Cancer
Slide 16: LGSOC Unmet Need & Opportunity
LGSOC Unmet Need & Opportunity • LGSOC is a less common type of ovarian cancer that is often diagnosed in younger women o LGSOC is a unique disease that is distinct from high-grade serous ovarian cancer (HGSOC) in its pathology, protracted clinical course and low response to chemotherapy and thus re
Slide 17: LGSOC is a Unique RAS Pathway-Driven Cancer with a High Unmet Need
LGSOC is a Unique RAS Pathway-Driven Cancer with a High Unmet Need ~30% of LGSOC Patients Have KRAS mt LGSOC is a type of ovarian cancer that disproportionately ~70% of LGSOC Shows RAS Pathway-Associated mts affects younger women 1,000 to 2,000 patients in the U.S. and 15,000 to 30,000 worldwide dia
Slide 18: Low-Grade and High-Grade Serous Ovarian Cancer Are Different Diseases
Low-Grade and High-Grade Serous Ovarian Cancer Are Different Diseases Variable LGSOC HGSOC Nuclear atypia Uniform round to +++ oval with little Marked variation variation Mitotic Index <12 mitoses per >12 mitoses per 10 hpf 10 hpf Chromatin and Little Marked (nuclear LGSOC variation in size of size
Slide 19: Recurrent LGSOC: High Medical Need, No Approved Treatment Options
Recurrent LGSOC: High Medical Need No Approved Treatment Options – Limited Benefit from Available Therapies Recurrent Low-Grade Ovarian Cancer – Treatment Guidelines 1 No Category 1 recommendations (high-level evidence). Category 2a (lower-level evidence with uniform NCCN consensus) unless otherwise
Slide 20: Recent LGSOC Trials Highlight High Unmet Need
Recent LGSOC Trials Highlight High Unmet Need Number of Prior Prior Discontinuation Systemic Prior Response Rate Image Median PFS Trial MEK Therapy Rate Therapies Bevacizumab ORR Assessment Months (95% CI) allowed due to AEs Median (range) SoC 6% INV 7.2 (5.6-9.9) 30% GOG 2 (n=130) 95% CI: (3%, 12%)
Slide 21: FRAME Study: High Rate of Durable Responses with Avutometinib and Defactinib
FRAME Study: High Rate of Durable Responses with the Combination of Avutometinib and Defactinib in Recurrent Low Grade Serous Ovarian Cancer (n=26) • Overall response rate (ORR) = 42% (11 confirmed PRs/26) o KRAS mutant ORR = 58% (7 confirmed PRs/12) o KRAS wild-type ORR = 33% (4 confirmed PRs/12) P
Slide 22: RAMP 201: Registration-Directed Phase 2 Trial in Recurrent LGSOC
RAMP 201 (ENGOTov60/GOG3052): Registration-Directed Phase 2 Trial of Avutometinib ± Defactinib in Patients with Recurrent LGSOC Part A Part B Part C Part D Selection Phase* Expansion Phase* Expansion Phase* Expansion Phase** Combo (Combo Lower Dose) Avutometinib + Defactinib Avutometinib + Def
Slide 23: Updated Data from Part A of RAMP 201
ASCO 2023 data Updated Data from Part A of RAMP 201 Avutometinib + Defactinib Total (n=29) 45% (13) 95% CI: (26%, 64%) ORR, % (n) KRAS mt KRAS wt 60% (9/15) 29% (4/14) Tumor shrinkage, % (n) 86% (25) Median Time to Response 5.5 months (range 1.6-14.7 months) Relative Dose Intensity 83% ± 20% • 29 pa
Slide 24: Current Trials with Avutometinib + Defactinib Show ORR >40%
Recent LGSOC Trials with Standard of Care Highlight High Unmet Need: Current Trials with Avutometinib + Defactinib Show Overall Response Rate >40% Median Prior Prior Discontinuation Number of Response Rate Image Median PFS Trial MEK Bevacizu Therapy Rate Prior lines ORR Assessment Months (95% CI) Al
Slide 25: RAMP 201 Part A: Heavily Pre-Treated Patient Population
ASCO 2023 data RAMP 201 Part A: Heavily Pre-Treated Patient Population Prior Platinum-Based Chemotherapy, Endocrine Therapy, Bevacizumab in Most Patients; Prior MEK Inhibitor Therapy was Permitted Avutometinib Monotherapy Avutometinib + Defactinib KRAS mt KRAS wt Total KRAS mt KRAS wt Total (n=16) (
Slide 26: RAMP 201 Part A: Evaluable Patient Population
ASCO 2023 data RAMP 201 Part A: Evaluable Patient Population* Positive ORR Confirmed by Blinded Independent Central Review (BICR) Support Avutometinib + Defactinib as Go Forward Regimen in LGSOC - Regardless of KRAS Status Avutometinib Avutometinib + Defactinib KRAS mt KRAS wt Total KRAS mt KRAS wt
Slide 27: Best Response (% change from baseline)
ASCO 2023 data Combination of Avutometinib and Defactinib High Disease Control Rate + Tumor Reduction in Recurrent LGSOC RAMP 201 (Part A) Part A (Evaluable for Efficacy *) N=29 Evaluable for Efficacy * +117.7% Confirmed ORR: 45% 20 ** (% change from baseline) Confirmed/Unconfirmed ORR: 52% 0 Diseas
Slide 28: Initial Data from RAMP 201 Reinforce Findings from FRAME
ASCO 2023 data Combination of Avutometinib and Defactinib Initial Data from RAMP 201 Trial Reinforce Findings from FRAME Trial RAMP 201 (Part A) FRAME Interim Analysis - Blinded ICR Investigator Assessment +117.7% N=29 N=26 20 20 ** (% change from baseline) 0 (% change from baseline) 0 Best Response
Slide 29: RAMP 201: Safety and Tolerability Profile
ASCO 2023 data RAMP 201: Safety and Tolerability Profile of Avutometinib + Defactinib No New Safety Signals; Few Discontinuations Due to Adverse Events Avutometinib + Defactinib (n=81) Most Common Treatment-Related Adverse Any Grade Grade ≥3 Events (>20%) in All Treated Patients Nausea, n (%) 50 (61
Slide 30: Plan to File for Accelerated Approval with Mature RAMP 201 and FRAME Results
Plan to File for Accelerated Approval with Mature RAMP 201 and FRAME Study Results Update Next Steps • Combination of avutometinib with defactinib selected • Target enrollment for primary analysis (n=72) in as go forward treatment regimen combination has been achieved • Combination development conti
Slide 31: RAMP-301: Forward Plan Confirmatory Randomized Controlled Trial
RAMP-301: Prospective Randomized Controlled Trial Forward Plan: Confirmatory Trial – Randomized Controlled Trial (RCT) Avutometinib + Defactinib* Primary Endpoint: Recurrent LGSOC Progression-Free Survival (PFS) by BICR** Recurrent LGSOC (N=135) KRAS mt+wt Avutometinib + Prior platinum Defact
Slide 32: RAMP 201 Part A Interim Data Support Meaningful Market Potential
RAMP 201 Part A Interim Data Support Meaningful Market Potential for All Recurrent LGSOC Regardless of KRAS Status with Long Duration of Therapy Prevalence Patient-months of Therapy Per Year2 (across all 2L+ patients) ~6K - 50,000 100,000 150,000 patients US1 NSCLC KRAS G12C3 Pancreatic Cancer3 LGSO
Slide 33: Avutometinib Combinations in Non-Small Cell Lung Cancer
Avutometinib Combinations in Non-Small Cell Lung Cancer
Slide 34: High Unmet Need in Refractory KRAS & BRAF mt NSCLC Adenocarcinoma
High Unmet Need in Refractory KRAS & BRAF mt NSCLC Adenocarcinoma Advanced or Metastatic NSCL Cancer NSCLC Adenocarcinoma3 Recommend Histologic and Molecular Subtyping5 15 EGFR/ALK/ROS1/BRAF/ Non-targeted Non-Targeted KRAS G12C (targeted) PD-(L)1 ≥ 1% PD-(L)1 < 1% US Annual Incidence7,8: 114K WW Ann
Slide 35: Preclinical Synergy of Avutometinib + G12C Inhibitors in KRAS G12C Models
Preclinical Synergy of Avutometinib + G12C Inhibitors in KRAS G12C Models Avutometinib & FAKi potentiate sotorasib efficacy in KRAS G12C Synergy of avutometinib + G12C inhibitors across NSCLC in vivo; Tumor regression in all mice with triple combination G12C mutant NSCLC, CRC & Pancreatic cancer cel
Slide 36: Avutometinib ± FAKi Restores Anti-Tumor Efficacy of Sotorasib
Avutometinib ± FAKi Restores Anti-Tumor Efficacy of Sotorasib in G12Ci-Resistant KRAS G12C Models Avutometinib is effective against acquired KRAS mutations that Addition of avutometinib + FAK inhibitor to sotorasib increases tumor growth inhibition occur clinically upon progression on G12C inhibitor
Slide 37: RAMP 203: Phase 1/2 Trial of Avutometinib + Sotorasib
RAMP 203: Phase 1/2 Trial of Avutometinib + LUMAKRASTM (Sotorasib) in KRAS G12C Advanced NSCLC Part A: Dose Evaluation Part B: Dose Expansion at RP2D (3+3 DLT Assessment) (Primary endpoint ORR) Now enrolling expansion phase Patients must have a KRAS G12C mutation Cohort 1 determined using validate
Slide 38: RAMP 203: Objective Responses in KRAS G12C NSCLC
RAMP 203: Objective Responses in KRASG12C NSCLC Sotorasib + Avutometinib Combination *On treatment at time of data cutoff; + Patient with -38.4% tumor reduction classified as SD due to disease progression prior to confirmatory scan. Reference: Awad et al., EORTC- NCI – AACR Conference Oct 2023 38
Slide 39: RAMP 204: Phase 1/2 Trial of Avutometinib + Adagrasib
RAMP 204: Phase 1/2 Trial of Avutometinib + KRAZATITM (Adagrasib) in KRAS G12C Advanced NSCLC Part A: Dose Evaluation Part B: Dose Expansion Patients must have a (3+3 DLT Assessment) (Primary endpoint ORR) KRAS G12C mutation determined using validated test Treatment with at least 1 but no more S
Slide 40: RAMP 202: Phase 2 Trial in BRAF mt NSCLC
RAMP 202: Phase 2 Trial of Avutometinib + Defactinib in BRAF mt NSCLC Initial Phase Analysis Patients with Advanced NSCLC 1-2 prior regimens 1 prior platinum-containing Avutometinib + chemo Defactinib1 Prior CPI unless BRAF V600E contraindicated BRAF Mutant n=15 Expansion TBD Measurable di
Slide 41: Additional Combinations and Programs
Additional Combinations and Programs
Slide 42: Avutometinib + FAKi with Chemotherapy in Pancreatic Cancer Mouse Model
Addition of Avutometinib + FAKi to Chemotherapy Induces Tumor Regression and Increases Survival in a KRAS/p53 Pancreatic Cancer Mouse Model Survival vehicle 100 vehicle gemcitabine/paclitaxel GEM/PTX Percent survival 80 Avutometinib/FAKi 60 Avutometinib/FAKi 40 + GEM/PTX avutometinib/FAKi 20 avutome
Slide 43: RAMP 205: Phase 1/2 Trial in Metastatic Pancreatic Cancer
RAMP 205: Phase 1/2 Trial of Avutometinib/Defactinib + GEMZARTM (Gemcitabine)/ABRAXANETM (Nab-paclitaxel) in Front Line Metastatic Pancreatic Cancer Part A: Dose Evaluation Part B: Dose Expansion at RP2D (3+3 DLT Assessment) (Primary endpoint ORR) Patients with confirmed metastatic pancreatic duct
Slide 44: Avutometinib with anti-EGFR mAb in KRAS mt Colorectal PDX Model
Combination of Avutometinib with anti-EGFR mAb Induces Tumor Regression in a KRAS mt Colorectal PDX Model • Avutometinib + anti-EGFR (panitumumab) induces tumor regression in a KRAS mutant CRC patient-derived xenograft model vehicle • G12Ci + anti-EGFR (sotorasib + panitumumab and adagrasib + cetuxi
Slide 45: Discovery Efforts and Financials
Discovery Efforts and Financials
Slide 46: Collaboration with GenFleet Strengthens Pipeline Targeting RAS Pathway-Driven Cancers
Discovery and Development Collaboration with GenFleet Strengthens Pipeline Targeting RAS Pathway-Driven Cancers • Increases the breadth of Verastem’s oncology pipeline with strategically-aligned RAS pathway focus o Exclusive option for Verastem to license up to 3 programs with development and commer
Slide 47: Key Financial Statistics
Key Financial Statistics As of and for the quarter ended September 30, 2023 Cash, cash equivalents & investments $165.7M GAAP Operating Expenses $21.3M Non-GAAP Operating Expenses* $19.8M Shares Outstanding 25.3M** Sources of Non-Dilutive Capital • Oxford Finance LLC Credit Facility • Up to $150M av
Slide 48: Avutometinib Patent Exclusivity
Avutometinib Patent Exclusivity Composition of Matter PTE Feb 2027 + 5 yrs (PTE) = 2032 Method of Making Sept 2032 Dosing Protocol May 2038 Combination w/ Defactinib Sept 2040 Methods of Treating 2041 - 2042 if issued Combinations 2041 - 2042 if issued 48
Slide 49: Experienced Senior Management Team
Experienced Senior Management Team Daniel Paterson Dan Calkins Cathy Carew President and Chief Executive Chief Organizational Chief Financial Officer Effectiveness Officer Officer CEO – The DNA Repair Co. (now Technical Accounting Consultant- Principal – HR Collaborative On-Q-ity) CFGI Ironw
Slide 50: Thank You
\W VERASTEM ONCOLOGY