Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (May 2024)
52 slides from Verastem's investor presentation, May 2024
Slide 1: Delivering Novel Therapies in RAS/MAPK Pathway Driven Cancers
Delivering Novel Therapies in RAS/MAPK Pathway Driven Cancers May 2024 Corporate Presentation
Slide 2: Disclaimers
Disclaimers Forward-Looking 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 Therapeutics
Slide 3: Positioned to Deliver on 2024 Catalysts
Positioned to Deliver on 2024 Catalysts ➢ On track to deliver the first approved therapy in LGSOC • Data from Part A of RAMP 201 showed avutometinib, a RAF/MEK Clamp, in combination with defactinib, a FAK inhibitor, demonstrated robust responses in patients with recurrent low-grade serous ovarian ca
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 Drug • Initial safety and effica
Slide 5: Clinical Program Designed to Maximize LGSOC and Beyond
Clinical Program Designed to Maximize LGSOC and Beyond IND-Enabling/ Trial/Regimen Phase 1 Phase 2 Phase 3 Anticipated Milestones Collaboration Preclinical Avutometinib + Defactinib: Recurrent LGSOC RAMP 301 RAF/MEK RAMP 301 Ongoing Enrollment Clamp + FAKi vs ICT RAMP 201 RAMP 201 Topline Data; Init
Slide 6: Avutometinib RAF/MEK Clamp Program Overview
Avutometinib RAF/MEK Clamp Program Overview
Slide 7: Avutometinib is a Differentiated Agent with Potential to Serve as Backbone for Combinations
Avutometinib is a Differentiated Agent with the Potential to Serve as the Backbone for Combinations Across RAS Pathway-Driven Cancers • Differentiated RAF/MEK clamp mechanism of action • Novel intermittent dosing schedule; convenient oral regimen • Orphan Drug Designation for avutometinib alone or i
Slide 8: Avutometinib is a Differentiated Small Molecule RAF/MEK Clamp
Avutometinib is a Differentiated 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 Collab
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: Scientific Rationale for Avutometinib and FAK Inhibitor Combination
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 defactinib avu
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: Avutometinib + Defactinib in Low-Grade Serous Ovarian Cancer
Avutometinib Defactinib in Low-Grade Serous Ovarian Cancer
Slide 13: 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 disease that is distinct from high-grade serous ovarian cancer (HGSOC) in its pathology, protracted clinical course and low response to chemotherapy and thus requires
Slide 14: LGSOC is a Distinct RAS Pathway-Driven Cancer with a High Unmet Need
LGSOC is a Distinct 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 d
Slide 15: 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 16: FRAME Study: High Rate of Durable Responses in Recurrent LGSOC
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 17: 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 18: 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 19: Recent LGSOC Trials with Standard of Care Highlight High Unmet Need
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 20: 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 21: 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 22: Combination of Avutometinib and Defactinib: High Disease Control Rate
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 23: Initial Data from RAMP 201 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 24: 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 25: 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 Endpoi
Slide 26: 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 Recent Achievements/Milestones • 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
Slide 27: Avutometinib with KRAS G12C Inhibitors in Non-Small Cell Lung Cancer
Avutometinib with KRAS G12C Inhibitors in Non-Small Cell Lung Cancer
Slide 28: 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 29: 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 30: Avutometinib + FAKi Restores Anti-Tumor Efficacy of Sotorasib in 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 31: RAMP 203: Phase 1/2 Trial of Avutometinib + Sotorasib
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 Completed enrollment KRAS G12C mutation
Slide 32: RAMP 203: Objective Responses in KRAS G12C NSCLC
RAMP 203: Objective Responses in KRAS G12C NSCLC Sotorasib + Avutometinib Combination Avutometinib + Sotorasib Percentage Change in Target Lesion Sum with time on treatment *On treatment at time of data cutoff; + Patient with -38.4% tumor reduction classified as SD due to disease progression prior t
Slide 33: 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 t
Slide 34: Avutometinib + Defactinib in Pancreatic Cancer
Avutometinib + Defactinib in Pancreatic Cancer
Slide 35: Avutometinib + FAKi with Chemotherapy Induces Tumor Regression in Pancreatic Model
Addition of Avutometinib + FAKi to Chemotherapy Induces Tumor Regression and Increases Survival in a KRAS/p53 Pancreatic Cancer Mouse Model Survival 100 vehicle Percent survival 80 gemcitabine/paclitaxel 60 40 avutometinib/FAKi 20 avutometinib/FAKi 0 + gemcitabine/paclitaxel 0 20 40 60 80 100 120 da
Slide 36: 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 37: Avutometinib Combination in Colorectal Cancer
Avutometinib Combination in Colorectal Cancer
Slide 38: Avutometinib with anti-EGFR mAb Induces Tumor Regression in KRAS mt Colorectal 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 39: RAS Pathway-Driven Cancers and Rational Avutometinib Combinations
RAS Pathway-Driven Cancers and Rational Avutometinib Combinations
Slide 40: Investigator-Sponsored Trials Provide Comprehensive Approach to Blockade of RAS Pathway
Investigator-Sponsored Trials Provide Ongoing Comprehensive Approach to Establish More Complete Blockade of RAS Pathway & Resistance Pathways Incidence/ Biomarker Indication Regimen Setting Phase Institution Prevalence % Memorial Sloan Prevalence Avutometinib + defactinib + Low-grade serous ovarian
Slide 41: Discovery Efforts
Discovery Efforts
Slide 42: 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 options for Verastem to exclusively license up to 3 programs with developme
Slide 43: Rationale for Designing an Oral Inhibitor of KRAS G12D (ON/OFF)
Rationale for Designing a Potent and Selective Orally Bioavailable Inhibitor of KRAS G12D (ON/OFF) for the Treatment of Patients with KRAS G12D Cancers KRAS G12D is the most frequent Ideal to inhibit both the active (ON) & inactive (OFF) states KRAS mutation in human cancer of KRAS for deep and dura
Slide 44: GFH375 (VS-7375) is an Oral KRAS G12D (ON/OFF) Inhibitor
GFH375 (VS-7375) is an Oral KRAS G12D (ON/OFF) Inhibitor First program from the GenFleet collaboration Dual inhibitor of ON (GTP) and OFF (GDP) • GFH375 (VS-7375) is a potent and selective orally states of KRAS G12D bioavailable inhibitor of KRAS G12D (ON/OFF) with potent anti-tumor efficacy demonst
Slide 45: Financials
Financials
Slide 46: Key Financial Statistics
Key Financial Statistics As of and for the quarter ended March 31, 2024 Cash, cash equivalents & investments $110.1M GAAP Operating Expenses $28.1M Non-GAAP Operating Expenses* $26.6M Shares Outstanding 25.3M** Sources of Non-Dilutive Capital • Oxford Finance LLC Credit Facility • Up to $150M availa
Slide 47: Thank You
W VERASTEM ONCOLOGY
Slide 48: Addendum
Addendum
Slide 49: 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 10 >12 mitoses per 10 hpf hpf Chromatin and Little Marked (nuclear LGSOC variation in size of size
Slide 50: 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 51: 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 51
Slide 52: Experienced Senior Management Team
Experienced Senior Management Team Daniel Paterson Dan Calkins Cathy Carew Mike Crowther John Hayslip, M.D. Jonathan Pachter, Colleen Mockbee President and Chief Chief Financial Chief Organizational Chief Commercial and Chief Medical Officer Ph.D. Global Head of Executive Officer Officer Effectivene