Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (March 2024)
49 slides from Verastem's investor presentation, Mar 14, 2024
Slide 1: Delivering Novel Therapies in RAS/MAPK Pathway Driven Cancers
Delivering Novel Therapies in RAS/MAPK Pathway Driven Cancers March 2024 Corporate Presentation
Slide 2: Disclaimers
Disclaimers This presentation includes forward-looking statements about Verastem Oncology’s programs and product candidates, strategy, future plans and prospects, including statements related to the expected outcome and benefits of collaborations, including with GenFleet, the potential clinical valu
Slide 3: Well-Positioned To Deliver on 2024 Catalysts
Well-Positioned To Deliver on 2024 Catalysts ➢ On track to deliver the first approved therapy in LGSOC • Data at ASCO 2023 of avutometinib, a RAF/MEK Clamp in combination with defactinib, a FAK inhibitor, demonstrated robust responses in patients with recurrent low-grade serous ovarian cancer (LGSOC
Slide 4: Driving Momentum in 2024: Recap of Recent Key Achievements
Driving Momentum in 2024: Recap of Recent Key Achievements Avutometinib + Avutometinib + Defactinib: Avutometinib + KRAS GFH375/VS-7375: Defactinib: Metastatic Pancreatic G12C Inhibitors: Oral G12D (ON/OFF) Recurrent LGSOC Cancer NSCLC Inhibitor ✓ Received FDA Orphan ✓ Initiated RAMP 205 combo ✓ Rec
Slide 5: Clinical Program Designed for Success in LGSOC, Signal Generation
Clinical Program Designed for Success in LGSOC, Signal Generation IND-Enabling/ Regimen Phase 1 Phase 2 Phase 3 Anticipated Milestones Collaboration Preclinical Avutometinib + Defactinib: Recurrent LGSOC RAF/MEK RAMP 301 Ongoing Enrollment Clamp + FAKi RAMP 201 Topline Data; RAF/MEK Rolling NDA Subm
Slide 6: Avutometinib RAF/MEK Clamp Program Overview
Avutometinib RAF/MEK Clamp Program Overview
Slide 7: Avutometinib is a Differentiated Agent with the Potential to Serve as the Backbone for Combinations
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 • Orphan Drug Designation for avutometinib alone or in combin
Slide 8: 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 9: Avutometinib Inhibits Cell Proliferation Across Multiple RAS/MAPK Pathway Alterations
Avutometinib Inhibits Cell Proliferation Across Multiple RAS/MAPK Pathway Alterations and Multiple Solid Tumor Histologies Avutometinib IC50 (3D proliferation assay) KRAS G12C KRAS G12D KRAS G12V Other KRAS mt BRAF mt NRAS mt NF1 mt Other mt Avutometinib IC50 (M) 10 1 0.1 0.01 NCI-H2405 NCI-H2087 N
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 Tumor growth KRAS mutant LGSOC PDX model Growth factors Extracellular Matrix pFAK RTK Integrin 150 300 vehicle α Tumor volume (mm3 +/- SEM) β 200 FAKi FAK defactin
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: Ongoing 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 Incidence2,3: Prevalence1: 114K RAMP301 6K 70% Avutometinib + defactinib Relapsed Refractory molecularly profiled LGSOC LG
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 301 Confirmatory Randomized Controlled Trial LGSOC1 Avutometinib +
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
Best response by RECIST FRAME Study: High Rate of Durable Responses with the Combination of Avutometinib and Defactinib in Recurrent LGSOC (n=26) KRAS D57-T58ins KRAS D33E, I24N Undocumented Undocumented KRAS G12D KRAS G12A KRAS G12V KRAS G12D KRAS G12D KRAS G12D KRAS G12D KRAS G12V KRAS G12D KRAS G
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 + D
Slide 23: Updated Data from Part A of RAMP 201
ASCO 2023 data “These results demonstrate Updated Data from Part A of RAMP 201 avutometinib in combination with defactinib can deliver high Avutometinib + Defactinib response rates for patients with Total (n=29) recurrent LGSOC with a promising 45% (13) 95% CI: (26%, 64%) safety profile to date. It
Slide 24: Current Trials with Avutometinib + Defactinib Show Overall Response Rate >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: High Disease Control Rate + Tumor Reduction in Recurrent LGSOC
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 Trial Reinforce Findings from FRAME Trial
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) (% change from baseline) 0 0 Best Response
Slide 29: RAMP 201: Safety and Tolerability Profile of Avutometinib + Defactinib
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: RAMP-301: Phase 3 Confirmatory Randomized Controlled Trial
❖RAMP-301: Avutometinib + Defactinib Phase 3 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 Defactinib* Secondary Endp
Slide 31: 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 32: 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 • Encouraging efficacy results include independently Next Milestones confirmed responses (FRAME study) • Plan to file for accelerated approval based on the • RAMP 201 Part A data at ASCO 2023 totality of the data from
Slide 33: Avutometinib with KRAS G12C Inhibitors in Non-Small Cell Lung Cancer
Avutometinib with KRAS G12C Inhibitors in Non-Small Cell Lung Cancer
Slide 34: High Unmet Need in Refractory NSCLC Adenocarcinoma
High Unmet Need in Refractory 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 Annual Incidence1,
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 in G12Ci-Resistant Models
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 in KRAS G12C NSCLC
RAMP 203: Phase 1/2 Trial of Avutometinib + LUMAKRASTM (Sotorasib) Defactinib 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 u
Slide 38: RAMP 203: Objective Responses in KRAS G12C NSCLC
RAMP 203: Objective Responses in KRAS G12C 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. 38 Reference: Awad et al., EORTC- NCI – AACR Conference Oct 2023
Slide 39: RAMP 204: Phase 1/2 Trial of Avutometinib + Adagrasib in KRAS G12C NSCLC
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 t
Slide 40: Avutometinib Combinations in Pancreatic Cancer and Colorectal Cancer
Avutometinib Combinations in Pancreatic Cancer and Colorectal Cancer
Slide 41: Avutometinib + FAKi with Chemotherapy Induces Tumor Regression in Pancreatic 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 Percent survival 80 GEM/PTX Avutometinib/FAKi 60 Avutometinib/FAKi 40 + GEM/PTX avutometinib/FAKi 20 avutome
Slide 42: RAMP 205: Phase 1/2 Trial in Front Line 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 43: Avutometinib with anti-EGFR mAb Induces Tumor Regression 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 44: Discovery Efforts and Financials
Discovery Efforts and Financials
Slide 45: Discovery and Development Collaboration with GenFleet Strengthens Pipeline
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 46: Key Financial Statistics
Key Financial Statistics As of and for the quarter ended December 31, 2023 Cash, cash equivalents & investments $137.1M GAAP Operating Expenses $31.1M Non-GAAP Operating Expenses* $29.5M Shares Outstanding 25.3M** Sources of Non-Dilutive Capital • Oxford Finance LLC Credit Facility • Up to $150M ava
Slide 47: 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 Solid Form Dec 2042 Methods or Treating; Combinations 2041 - 2042 if issued 47
Slide 48: 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 49: Thank You
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