Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (June 2024)
61 slides from Verastem's investor presentation, Jun 26, 2024
Slide 1: Delivering Novel Therapies in RAS/MAPK Pathway Driven Cancers
Delivering Novel Therapies in RAS/MAPK Pathway Driven Cancers June 2024 Corporate Presentation
Slide 2: Disclaimers: Forward-Looking Statements
2 Disclaimers F orward - Looking Statements This presentation includes forward - looking statements about, among other things, Verastem Oncology’s (the “Company”) programs and product candidates, strategy, future plans and prospects, including statements relate d to the timing, scope and progress of
Slide 3: Verastem Oncology: Preparing to Commercialize First Novel RAS/MAPK Combo Asset
3 Verastem Oncology: Preparing to Commercialize First Novel RAS/MAPK Combo Asset with Billion - Dollar Addressable Market Opportunity Avutometinib and defactinib combo has the potential to become the first and only FDA approved treatment for recurrent LGSOC as soon as 2025 Partnership with GenFleet
Slide 4: Pipeline Assets Have Potential to Provide Significant Market Opportunity
4 Pipeline Assets Have the Potential to Provide Significant Market Opportunity in Both Short - and Long - Term Anchor: Avutometinib + Defactinib in Recurrent LGSOC in U.S. Maximize Potential: Additional Indications: PDAC, NSCLC, etc. Future Growth: Pipeline Expansion with G12Di and other programs Br
Slide 5: Lead Program: Avutometinib + Defactinib Inhibits Multiple Resistance Mechanisms
5 • Novel combination of avutometinib, a RAF/MEK clamp, and defactinib, a FAK inhibitor, offers a complementary MOA not achievable with previous MEK - only inhibitors • C linical activity in various RAS pathway - driven cancers, including in patients whose tumors previously progressed on other MEK i
Slide 6: Clinical Program Designed to Address LGSOC and Beyond
6 Clinical Program Designed to Address LGSOC and Beyond Trial/Regimen IND - Enabling/ Preclinical Phase 1 Phase 2 Phase 3 Anticipated Milestones Collaboration Avutometinib + Defactinib: Recurrent LGSOC RAMP 301 RAF/MEK Clamp + FAKi vs ICT RAMP 301 Ongoing Enrollment RAMP 201 RAF/MEK Clamp + FAKi Pla
Slide 7: Avutometinib + Defactinib Potential Approval in 2025 for Recurrent LGSOC
Avutometinib + Defactinib Potential Approval in 2025 for Recurrent Low - Grade Serous Ovarian Cancer
Slide 8: Potential New Treatment Option for Recurrent LGSOC on Accelerated Timeline
8 Potential to Bring a New Treatment Option for Recurrent LGSOC with Substantially Improved Outcomes on an Accelerated Timeline 1. Feb. 2024 data cutoff; 1. VSTM DOF, ATU 2024 (n=96, Fielded December 2023 – January 2024); 2. Refer to breakdown of market opportunity on slide 11. SoC: Standard of Care
Slide 9: High Unmet Need for Effective Therapy in Recurrent LGSOC
9 KRAS mt, 30% NRAS, BRAF, ARAF Mutant, 20% Non - RAS associated, 30% Other RAS - associated gene mutations, 20% U.S. Incidence: 1k - 2k 12 U.S. Prevalence: 6k - 8k 13 Worldwide: 80,000 80%+ of patients will experience a recurrence 1 Affects younger population and disproportionately impacts health,
Slide 10: Combo Has Potential to Address Key Treatment Needs
10 Avutometinib + Defactinib Combo Has the Potential to Address Key Treatment Needs • To date, avutometinib + defactinib combination data in recurrent LGSOC show: • Clinically meaningful response rates and durable benefit 1 • Strong Clinical Benefit Rate in patients with KRAS mutant or wild - type t
Slide 11: Start of Rolling NDA Supported by RAMP 201 Initial Topline Results
11 Start of Rolling NDA Submission Supported by RAMP 201 Initial Topline Results with Minimum of 5 Months Follow Up Discontinuation Rates Due to Adverse Events Remain Low 2 ORR Overall Population (Confirmed ORR by BICR) 27% (29/109) 1 95% CI (19%, 36%) KRAS mt 37% (21/57) KRAS wt 15% (8/52) Cl
Slide 12: Recent LGSOC Trials with Standard of Care Highlight High Unmet Need
12 Recent LGSOC Trials with Standard of Care Highlight High Unmet Need Trial Image Assessment Median Number of Prior lines of Therapy Prior MEK Allowed Therapy Response Rate ORR Discontinuation Rate Due to AEs GOG 281 1 INV 2 (1 - 10) No Standard of Care** 6% ^ 95% CI: (3%, 12%) 30% MILO 2 BICR 2* (
Slide 13: KOL Feedback on Avutometinib + Defactinib in Recurrent LGSOC
13 KOL Feedback on Avutometinib + Defactinib in Recurrent LGSOC Reinforces Opportunity to Address Unmet Treatment Needs “We are very excited about the recent data reported for the RAMP 201 study and initiation of the rolling submission . An overall response rate of close to 30 % in heavily pretreate
Slide 14: Potential to Rapidly Penetrate Current Prevalent Patient Population
14 Potential for Avutometinib + Defactinib to Rapidly Penetrate the Current Prevalent Patient Population, if Approved STAGE II - IV DISEASE 1 MOS: ∼ 10 YEARS 2 FRONTLINE TREATMENT INITIAL RECURRENCE SUBSEQUENT RECURRENCE ± Neoadjuvant platinum/ taxane Debulking surgery ± Platinum/ taxane chemotherap
Slide 15: LGSOC Indication Represents Significant Market Opportunity
15 LGSOC Indication Represents Significant Market Opportunity Anticipate high market penetration in LGSOC KRAS mt population given: • No FDA approved therapies for LGSOC • High adoption rate based on Survey of Oncologists 4 Plan to address prevalent population over 3 - 5 years from launch: • Patient
Slide 16: Efficiently Scaled Commercial Model to Deliver Best-In-Class Launch
16 Efficiently Scaled Commercial Model to Deliver Best - In - Class Launch HCO/Key Accounts Patients GPO ▪ Patient support and access programs ▪ Best - in - class multichannel marketing ▪ NPP pull through and reinforcement to targeted customers and white space territories ▪ Inside Sales Reps will bo
Slide 17: Regulatory Approach Pursuing Broadest Label Possible
17 • Seeking Accelerated Approval, ORR and DoR are main efficacy outcomes • No FDA approved treatments • Current SoC therapy is associated with low response rates and high discontinuation rate due to toxicity • Avutometinib + Defactinib clinical data shows advantage over available therapy Regulatory
Slide 18: Multi-Pronged Approach to Access for KRAS Wild-Type LGSOC
18 Multi - Pronged Approach to Ensure Patients with Recurrent KRAS Wild - Type LGSOC Will Have Access to Avutometinib + Defactinib, if Approved Leverage the Phase 3 RAMP 301 study primary endpoint of PFS Submit RAMP 201, inclusive of entire patient population, for publication and NCCN consideration
Slide 19: RAMP 201 and RAMP 301 Study Designs
19 • Patients enrolled with recurrent KRAS mt and KRAS wt LGSOC; prior chemo and MEKi use allowed • Primary Endpoint: ORR • Determined avutometinib 3.2 mg BIW + defactinib 200 mg BID combination as go forward regimen based on greater antitumor activity and tolerability profile vs avutometinib 4.0 mg
Slide 20: Next Steps in LGSOC Clinical Program and NDA
20 Next Steps in LGSOC Clinical Program and NDA Plan to announce mature data from RAMP 201 in H2 2024 Expect to engage with FDA upon mature RAMP 201 dataset to discuss KRAS wt data and potential inclusion in NDA indication Expect to complete NDA submission in H2 2024 Expect to submit mature RAMP 201
Slide 21: Market Expansion in First-line Metastatic Pancreatic and Advanced Lung Cancer
Avutometinib ± Defactinib Potential Market Expansion Opportunities in First - line Metastatic Pancreatic Cancer and Advanced Lung Cancer
Slide 22: Topline Data from RAMP 205 in First-Line Metastatic Pancreatic Cancer
Topline Data from RAMP 205: Avutometinib + Defactinib + SOC in First - Line Metastatic Pancreatic Cancer
Slide 23: RAMP 205: Designed to Identify and Evaluate RP2D
23 RAMP 205: Designed to Identify and Evaluate RP2D in C ombination with Chemotherapy for Tr eatment of Newly Diagnosed mPDAC Inclusion Criteria Part A: Dose Evaluation (3+3 DLT Assessment) Part B: Dose Expansion (Primary Endpoint: ORR) • Histologic or cytologic confirmed metastatic pancreatic ducta
Slide 24: RAMP 205: Initial Interim Safety and Efficacy Results
24 RAMP 205: Initial Interim Safety and Efficacy Results • Encouraging early interim data from ongoing Phase 1/2 RAMP 205 study evaluating avutometinib + defactinib + gemcitabine + Nab - paclitaxel in first - line metastatic pancreatic cancer • As of data cutoff of May 14, 2024, Dose Level 1 mature
Slide 25: Landmark Trials in First-Line Metastatic Pancreatic Cancer
25 Landmark Trials in First - Line Metastatic Pancreatic Cancer Trial/PI/Reported (# Patients) Intervention Comparator ORR by Investigator (95% CI) mPFS (95% CI) mOS (95% CI) MPACT Von Hoff 2013 (N=861) Gem/NabP * (n=431) Gem (n=430) Gem/NabP 5.5 months (4.5 - 5.9) 8.5 months (7.89 - 9.53) 29% (25 -
Slide 26: RAMP 205: Evaluating Multiple Regimens in Parallel
26 RAMP 205: Evaluating Multiple Regimens in Parallel to Efficiently Identify RP2D in First - Line mPC Duration of Treatment for All Patients; Safety Population (n=41) Data Cutoff Date:14 MAY 2024 Source: Program: F_TR_SWIMMER.sas In Dose Level 1: • 1 of 6 patients achieved objective response by mon
Slide 27: RAMP 205: Best Percent Change in Target Lesion Sum
27 RAMP 205: Best Percent Change in Target Lesion Sum of Diameters Includes Patients Who Have Had At Least First Scan (n=26) Data Cutoff Date:14 MAY 2024 Source: Program: F_TR_WATERFALL_BYDOSE2 Threshold for PR Dose Level Avuto Defactinib Gem Nab - Pac Day 1, 8, 15 chemo dosing: - 1 2.4 mg BIW 200 m
Slide 28: RAMP 205: Treatment-Emergent Adverse Events
28 • Any grade TEAEs occurring in ≥20% or grade ≥3 occurring in ≥5% of patients 1 DL - 1 (n=11) DL1 (n=6) DL1a (n=12) DL2a (n=12) Total (N=41) Any Grade, n (%) Grade ≥3, n (%) Any Grade, n (%) Grade ≥3, n (%) Any Grade, n (%) Grade ≥3, n (%) Any Grade, n (%) Grade ≥3, n (%) Any Grade, n (%) Grade ≥3
Slide 29: Next Steps for RAMP 205
29 Next Steps for RAMP 205 Get mature data on all Dose Cohorts to determine RP2D for expansion cohort Plan to report updated data in Q1 2025 Evaluate development program options based on updated data
Slide 30: Avutometinib with KRAS G12C Inhibitors in NSCLC
Avutometinib with KRAS G12C Inhibitors in Non - Small Cell Lung Cancer
Slide 31: Preclinical Synergy of Avutometinib + G12C Inhibitors
31 0 10 20 30 0 500 1000 1500 2000 Tumor growth Days after first dose T u m o r v o l u m e ( m m 3 + / - S E M ) vehicle sotorasib sotorasib + avutometinib sotorasib + avutometinib + FAKi avutometinib trametinib **** **** **** Preclinical Synergy of Avutometinib + G12C Inhibitors in KRAS G12C Model
Slide 32: Avutometinib + FAKi Restores Sotorasib Activity in Resistant Models
32 Avutometinib FAKi Restores Anti - Tumor Activity of Sotorasib in G12Ci - Resistant KRAS G12C Models Avutometinib inhibits proliferation of cells harboring acquired KRAS mutations that occur clinically upon progression on G 1 2C inhibitors Addition of avutometinib + FAKi restores anti - tumor acti
Slide 33: RAMP 203: Phase 1/2 Trial with Sotorasib
33 Cohort 1 Patients without Prior KRAS G12C Inhibitor Treatment Stage 1 : ~20 patients Stage 2 : expand to 54 Inclusion Criteria Part A: Dose Evaluation (3+3 DLT Assessment) Part B: Dose Expansion (Primary endpoint: ORR) • Documented KRAS G12C mutation determined using validated test • Treatment wi
Slide 34: RAMP 203: Objective Responses in KRAS G12C NSCLC
34 *On treatment at time of data cutoff; + Patient with - 38.4% tumor reduction classified as SD due to disease progression prior to confirmatory scan. Awad et al., EORTC - NCI – AACR Conference Oct 2023 Avutometinib + Sotorasib Percentage Change in Target Lesion Sum with time on treatment RAMP 203:
Slide 35: RAMP 204: Phase 1/2 Trial with Adagrasib
35 • Documented KRAS G12C mutation determined using validated test • Treatment with >1 but no more than 3 prior systemic regimens, for Stage 3B - C or 4 NSCLC • Must have received prior therapy with a KRAS G12C inhibitor and experienced progressive disease • Measurable disease per RECIST v1.1 • ECOG
Slide 36: Next Steps for RAMP 203 and RAMP 204
36 Next Steps for RAMP 203 and RAMP 204 Continue study follow up on patients in both RAMP 203 and RAMP 204 Continue to add defactinib to RAMP 203 Expect to report updated interim data in H2 2024 from RAMP 203 Expect to report initial interim data in H2 2024 from RAMP 204
Slide 37: Ongoing Investigator-Sponsored Studies to Expand Avutometinib Indications
Ongoing Investigator - Sponsored Studies to Expand Avutometinib Indications and Combinations
Slide 38: Investigator-Sponsored Studies by Indication
38 Indication Incidence/ Prevalence Biomarker % Regimen Setting Phase Institution Gynecologic Cancers LGSOC Prevalence 6k 1 70% Avutometinib + defactinib + letrozole Low - grade serous ovarian cancer without prior systemic treatment Phase 1/2 Memorial Sloan Kettering Cancer Center Gynecologic Basket
Slide 39: Partnership with GenFleet Therapeutics
Partnership with GenFleet Therapeutics on Novel, Potential Best - in - Class RAS Pathway Programs
Slide 40: Discovery and Development Collaboration with GenFleet
40 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 to license up to 3 programs with development and commerciali
Slide 41: GFH375 (VS-7375) is an Oral KRAS G12D (ON/OFF) Inhibitor
41 GFH375 (VS - 7375) is an Oral KRAS G12D (ON/OFF) Inhibitor • GFH375 (VS - 7375) is a potent and selective orally bioavailable inhibitor of KRAS G12D (ON/OFF) with potent anti - tumor activity demonstrated across preclinical models • Dual inhibitor of ON (GTP) and OFF (GDP) states of KRAS G12D • O
Slide 42: Potent, Selective, Orally Bioavailable KRAS G12D (ON/OFF) Inhibitor
42 GEF GTP GDP GTP GDP KRAS G12D (ON/OFF) inhibitor RAS/MAPK pathway signaling GEF: Guanine nucleotide exchange factor GAP: GTPase - activating protein GAP P KRAS OFF (inactive) KRAS ON (active) Potent, Selective, Orally Bioavailable Inhibitor of KRAS G12D (ON/OFF) Provides Multiple Options for Clin
Slide 43: Next Steps for GFH375/VS-7375 & GenFleet Collaboration
43 Next Steps for GFH375/VS - 7375 & GenFleet Collaboration GenFleet is initiating a Phase 1/2 trial for GFH375/VS - 7375 in China in patients with G12D - mutated advanced solid tumors Expect to leverage the data in China study to accelerate a path forward in the U.S. and rest of world Ongoing disco
Slide 44: Achievements, Anticipated Milestones & Financials
Achievements, Anticipated Milestones & Financials
Slide 45: Verastem Poised to Become a Commercial-Stage Company
45 Verastem Poised to Become a Commercial - Stage Company with Significant Short - to Long - Term Opportunity Anchor: Avutometinib + Defactinib in Recurrent LGSOC in U.S. Maximize Potential: Additional Indications: PDAC, NSCLC, etc. Future Growth: Pipeline Expansion with G12Di and other programs Bro
Slide 46: Recent Corporate Achievements
46 Avutometinib + Defactinib: Recurrent LGSOC Avutometinib + Defactinib: Metastatic Pancreatic Cancer Avutometinib + KRAS G12C Inhibitors: NSCLC GFH375/VS - 7375: Oral G12D (ON/OFF) Inhibitor Recent Corporate Achievements x Received FDA Orphan Drug Designation x Initiated Phase 3 confirmatory study
Slide 47: Anticipated Milestones and Activities in H2 2024
47 Anticipated Milestones and Activities in H2 2024 Program Anticipated Milestones & Activities Avutometinib + Defactinib in Recurrent Low - grade Serous Ovarian Cancer (LGSOC) □ Plan to complete rolling NDA in H2 2024 □ Plan to announce mature data from RAMP 201 in H2 2024 • Continue site activatio
Slide 48: Key Financial Statistics
48 Key Financial Statistics Cash, cash equivalents & investments $110.1M GAAP Operating Expenses $28.1M Non - GAAP Operating Expenses* $26.6M Shares Outstanding 25.3M** As of and for the quarter ended March 31, 2024 • Oxford Finance LLC Credit Facility • Up to $150M available in a series of term loa
Slide 49: Verastem Oncology
W VERASTEM ONCOLOGY
Slide 50: Addendum
Addendum
Slide 51: Avutometinib Patent Exclusivity
51 Avutometinib Patent Exclusivity Composition of Matter Method of Making Sept 2032 Dosing Protocol May 2038 Combination w/ Defactinib Dec 2042 Feb 2027 + 5 yrs (PTE) = 2032 Sept 2040 Solid Form PTE 2041 - 2042 if issued Methods or Treating; Combinations
Slide 52: Experienced Senior Management Team
52 Experienced Senior Management Team Previous experience: • CEO, The DNA Repair Co. (now On - Q - ity ) • PharMetrics (now IMS) • Axion Daniel Paterson President and Chief Executive Officer Dan Calkins Chief Financial Officer Previous experience: • Technical Accounting Consultant - CFGI • PwC LLP C
Slide 53: Low-Grade and High-Grade Serous Ovarian Cancer Are Different Diseases
53 Low - Grade and High - Grade Serous Ovarian Cancer Are Different Diseases LGSOC HGSOC Nuclear atypia Uniform round to oval with little variation +++ Marked variation Mitotic Index <12 mitoses per 10 hpf >12 mitoses per 10 hpf Chromatin and variation in size of nucleus Little Marked (nuclear size
Slide 54: FDA Breakthrough Designation Based on FRAME Data
54 FDA Breakthrough Designation Based on FRAME Data Breakthrough Through Therapy Designation for combination of avutometinib and defactinib for treatment of recurrent LGSOC afte r o ne or more prior lines of therapy including platinum - based chemotherapy *Denis, 5 th Annual RAS - Targeted Drug Deve
Slide 55: RAMP 201 Study Design
55 RAMP 201 (ENGOTov60/GOG3052) Inclusion Criteria Recurrent LGSOC Prior chemotherapy Measurable disease (RECIST 1.1) Prior MEKi allowed Avutometinib + Defactinib KRAS mt (Total n=36) KRAS wt (Total n=36) N=72 (incl Part A+B) Avutometinib + Defactinib KRAS mt KRAS wt Expanded Enrollment +40 pts Avut
Slide 56: RAMP 301 Phase 3 Study Design
56 • Confirmed LGSOC diagnosis • Recurrent disease after prior platinum therapy • Documented KRAS mutation status • Measurable disease per RECIST v1.1 • Prior MEKi allowed • Prior Bevacizumab allowed Inclusion Criteria 1:1 Randomization n = 270 Stratification Factors: KRAS mutation status (wt vs. mt
Slide 57: Avutometinib is a Differentiated Small Molecule RAF/MEK Clamp
57 Avutometinib is a Differentiated Small Molecule RAF/MEK Clamp Contrasting Mechanism of Action vs. MEK - Only Inhibitors Coma et al., AACR 2022; Ishii et al., Cancer Res , 2013; Lito et al., Cancer Cell , 2014 RTK Growth factors Avutometinib RAS RAF MEK ERK Tumor Growth Avutometinib conc. (µmol/L)
Slide 58: Avutometinib Inhibits Cell Proliferation Across Multiple RAS/MAPK Alterations
58 Avutometinib Inhibits Cell Proliferation Across Multiple RAS/MAPK Pathway Alterations and Multiple Solid Tumor Histologies Verastem, unpublished data S W 1 4 6 3 M I A P A C A 2 H 3 5 8 H 1 3 7 3 S W 8 3 7 H 2 1 2 2 H 2 0 3 0 S W 1 5 7 3 H P A C A S P C 1 H P A F I I S N U - C 2 B L S 5 1 3 L S 1
Slide 59: Scientific Rationale for Avutometinib and FAK Inhibitor Combination
59 Scientific Rationale for Avutometinib and FAK Inhibitor Combination KRAS mutant LGSOC PDX model RTK RAS RAF MEK ERK YAP Growth factors β α Y397 Integrin FAK Extracellular Matrix SRC RhoA Tumor Growth P AKT defactinib Feedback Reactivation 0 10 20 30 0 100 200 300 Tumor growth Days after first dos
Slide 60: Optimized Dosing Schedule Defined
60 Optimized Dosing Schedule Defined: Favorable Tolerability Profile with Novel Intermittent Dosing Regimen Avutometinib monotherapy Daily at MTD N=6 28 - day cycle RP2D Avutometinib monotherapy 4mg twice weekly N=26 28 - day cycle RP2D (Avutometinib 3.2mg twice weekly + defactinib 200mg twice daily
Slide 61: NCCN Recommendations and Contemporary Clinical Data in LGSOC
61 NCCN Category 1 NCCN Category 2a NCCN Category 2b NCCN Category 3 General % Commercial Payer Coverage Recurrent LGSOC Treatment NCCN Recommendations and Contemporary Clinical Data in LGSOC No category 1 recommendation • 6 - 13% ORR and 17 - 30% discontinuation rate due to AEs • Based on GOG 281 a