Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (March 2025)
57 slides from Verastem's investor presentation, Mar 20, 2025
Slide 1: Delivering Novel Therapies for RAS/MAPK Pathway Driven Cancers
Delivering Novel Therapies for RAS/MAPK Pathway Driven Cancers Corporate Presentation | March 2025
Slide 2: Forward-Looking Statements
2 Forward - 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 anticipated timing of a potential launch o
Slide 3: Preparing to Commercialize First Novel RAS/MAPK/FAK Combo Asset
3 RAS: Rat Sarcoma; MAPK: Mitogen - activated protein kinases; FDA: Food and Drug Administration; LGSOC: Low - grade Serous Ovarian Cancer; PDUFA: Prescription Drug User Fee Act Verastem Oncology: Preparing to Commercialize First Novel RAS/MAPK/FAK Combo Asset with Billion - Dollar Addressable Marke
Slide 4: Efficiently Scaled Launch Model for KRAS Mutant Recurrent LGSOC
4 Efficiently Scaled Launch Model to Deliver Best - in - Class Launch for KRAS mutant Recurrent LGSOC in Mid - 2025 Mid - year Launch June 30, 2025 PDUFA Date Potential New Standard of Care Concentrated Launch Focus Significant Market Opportunity Novel/novel combination being reviewed under the Acce
Slide 5: Avutometinib and defactinib mechanism of action
5 1 AACR Genie v16.1; 2 Cheasley et al., J Pathol 2021; 3 Thomson et al., Gynecol Oncol 2023; 4 Gershenson et al., Gynecol Oncol 2022; 5 Coma et al., AACR 2022 ; 6 Ishii et al., Cancer Res, 2013 ; 7 Lito et al., Cancer Cell, 2014 ; 8 Lubrano et al., AACR 2024 ; 9 Banerji et al., AACR 2020 ; 10 Jones
Slide 6: Anticipated Milestones
6 Anticipated Milestones Phase 3 Phase 2 Phase 1 IND - Enabling/ Preclinical Discovery Phase Trial/Regimen Avutometinib + Defactinib : Recurrent LGSOC Complete enrollment in RAMP 301 by end of 2025 RAMP 301 RAF/MEK Clamp + FAKi vs ICT PDUFA Action Date: June 30, 2025 RAMP 201 RAF/MEK Clamp + FAKi Av
Slide 7: Near-Term Growth and Long-Term Pipeline Value
7 Image for illustrative purposes only. PDAC: pancreatic ductal adenocarcinoma cancer; NSCLC: non - small cell lung cancer Avutometinib Plus Defactinib Expected to Generate Near - Term Growth, while Pipeline Has Potential to Become Significant Driver for Long - Term Growth Value Time Anchor: Potenti
Slide 8: Avutometinib and Defactinib in Recurrent LGSOC
Avutometinib and Defactinib in Recurrent Low - Grade Serous Ovarian Cancer (LGSOC) PDUFA Action Date: June 30, 2025 Potential Launch in KRAS mutant Recurrent LGSOC in mid - 2025
Slide 9: Aiming to Deliver First FDA-Approved Treatment for KRAS Mutant Recurrent LGSOC
9 Verastem Aims to Deliver First FDA - Approved Treatment Specifically for KRAS Mutant Recurrent LGSOC in Mid - 2025 Avutometinib + Defactinib Demonstrated Durable Results Across Various Efficacy Measures in Heavily Pretreated Patients in RAMP 201 Clear Regulatory Path for KRAS Mutant • Under the Ac
Slide 10: High Unmet Need in Recurrent LGSOC
10 “When you get told that you have a recurrence, the mental load is a lot. You’re thinking, okay, what did I have to do for treatment the first time? Now I have to repeat that. And will there even be something available for me to take for a second, or a third recurrence?” - Amanda , real patient li
Slide 11: RAMP 201 Registration-Directed Phase 2 Trial Design
11 Numbers represent patients treated on study. RECIST: Response Evaluation Criteria in Solid Tumors; MEKi : Mitogen - activated extracellular signal - regulated kinase inhibitor; BICR, blinded independent central review; BID, twice daily; BIW, twice weekly; RP2D: Recommended Phase 2 Dose RAMP 201:
Slide 12: RAMP 201 Baseline Patient Characteristics
12 Avutometinib + Defactinib Regimen 3.2 mg BIW + 200 mg BID 3 weeks on / 1 week off* RAMP 201: Parts A+B+C Baseline Patient Characteristics KRAS wt N=57 KRAS mt N=58 All patients N=115 45 (21, 80) 60 (29, 87) 54 (21, 87) Age (years), Median (min, max) ECOG PS, n (%) 36 (63) 42 (72) 78 (68) 0 21 (37
Slide 13: RAMP 201 Response Rate
13 Avutometinib + Defactinib Regimen 3.2 mg BIW + 200 mg BID 3 weeks on / 1 week off Response Rate: Parts A, B, and C KRAS wt N=52 KRAS mt N=57 All patients N=109 9 (17) 25 (44) 34 (31) Confirmed* ORR, n (%) 0 2 (4) 2 (2) CR 9 (17) 23 (40) 32 (29) PR 34 (65) 28 (49) 62 (57) SD † , n (%) 7 (13) 2 (4)
Slide 14: Durable Responses and Disease Control in RAMP 201
14 Source for all data: RAMP 201 data cut off as of June 30, 2024 *KM estimates; NE = Could not be estimated based on number of pa tients with loss of response. Durable Responses and Disease Control Observed in RAMP 201 Study Avutometinib + Defactinib Regimen: Progression Free Survival (PFS) Avutome
Slide 15: Earlier Treatment Associated with Higher Response Rates
15 Source: SGO Annual Meeting on Women’s Cancer 2025; Source for all data: RAMP 201 data cut off as of June 30, 2024; Receiving Avutometinib and Defactinib Earlier in the Course of Therapy was Associated with Higher Rates of Response Regardless of KRAS Status 15 % 13 % 13 % 18 % 25 % 21 % 0 10 20 30
Slide 16: RAMP 201 Patient Disposition
16 Median follow - up = 13.6 mo (range, 1.4 – 39.5) Avutometinib + Defactinib Regimen 3.2 mg BIW + 200 mg BID 3 weeks on / 1 week off KRAS wt KRAS mt All patients 57 58 115 Patients Treated 8 (14) 24 (41) 32 (28) Patients on Treatment, n (%) 49 (86) 34 (59) 83 (72) Patients Discontinued Treatment, n
Slide 17: Treatment-Related Adverse Events
17 Avutometinib + Defactinib Regimen 3.2 mg BIW + 200 mg BID 3 weeks on/1 week off N= 115 Treatment - Related Adverse Events (>20% of patients)* n (%) Grade ≥3 All Grades Preferred term Non - laboratory AEs 3 (2.6) 77 (67.0) Nausea 9 (7.8) 67 (58.3) Diarrhea 1 (0.9) 61 (53.0) Oedema peripheral 3 (2.
Slide 18: RAMP 301 International Phase 3 Confirmatory Trial
18 BICR: blinded independent central review; BID: twice a day; BIW: twice a week; DCR: disease control rate; DoR : duration of response; INV: investigator; KRAS: kirsten rat sarcoma virus; MEKi : MEK inhibitor; mt: mutant; PO: per oral; pts, patients; ORR: objective response rate; OS: overall surviv
Slide 19: Changing the Treatment Paradigm in Recurrent LGSOC
PDUFA Action Date: June 30, 2025 Potential Launch in KRAS mutant Recurrent LGSOC in mid - 2025 Changing the Treatment Paradigm in Recurrent LGSOC
Slide 20: Patient Journey in LGSOC
20 Pre - Diagnosis Disproportionally affects younger women 1 Nonspecific signs and symptoms 2 Symptom Progression & Testing Treatment After Recurrence 1. B. Slomovitz , C. Gourley, M.S. Carey, et al., Low - grade serous ovarian cancer: State of the science, Gynecologic Oncology, https:// doi.org /10
Slide 21: Current Therapies Offer Poor Response Rates, High Discontinuation
21 1Study GOG 281 trial Gershenson et al., Lancet 2022; 2MILO Study. Grisham et al Clinical Cancer Research 2023, 3MILO Study Monk et al., J Clin Oncol 2020.; S oC = Standard of Care (endocrine / chemotherapy); INV = Investigator; BICR = Blinded Independent Central Review; PFS = Progression Free Sur
Slide 22: Combo Has Potential to Address Key Treatment Needs
22 1Data from RAMP 201 study June 30. 2024 cutoff; 2Chenard - Poirier, et al. ASCO 2017; References: Banerji, Q4 2020 report Avutometinib + Defactinib Combo Has the Potential to Address Key Treatment Needs To date, avutometinib + defactinib combination data in recurrent LGSOC show 1 : Long progressi
Slide 23: LGSOC Represents a Significant Market Opportunity
23 1. Estimated total addressable market opportunity based on incident / prevalent populations, average duration of therapy (as obs erved in VSTM clinical trials) and cost of therapy of $34,000 per month, consistent with other recent oncology drug launches (e.g. OJEMDA - $33,916 OGSIVEO - $29,000; w
Slide 24: Current Treatments on NCCN Guidelines
24 General source: NCCN; McGivney Global Advisory research and analysis; L.E.K. research and analysis. NCCN categories of prefer enc e: Preferred intervention, Other recommended intervention, Useful in certain circumstances. High - level of evidence generally means large randomized controlled Phased
Slide 25: Efficiently Scaled Launch Model
25 1VSTM DOF – Claims LGSOC Proxy; 2VSTM DOF. Self - identified patients with LGSOC registered via disease website; YTD: Year - to - date ; NPP: Non - personal promotion Efficiently Scaled Launch Model to Deliver Best - in - Class Launch for KRAS Mutant Recurrent LGSOC Surround Sound Support Program
Slide 26: Potential to Change Treatment Paradigm and Improve Outcomes
26 Potential to Change Treat Paradigm and Improve Patient Outcomes 1k - 2k incidence with a prevalence of 6k - 8k; potential for high market penetration in KRAS mutant at launch enriching overtime with the prevalent patient population Current available therapies offer limited efficacy, relatively hi
Slide 27: Next Steps in LGSOC Clinical Program and NDA
27 Next Steps in LGSOC Clinical Program and NDA Primary analysis from FRAME and RAMP 201 clinical trials anticipated to be published in H1 2025 Plan for FDA decision: June 30, 2025, PDUFA action date Plan to submit for NCCN guideline inclusion upon FDA approval Report initial data from the RAMP 201J
Slide 28: Market Expansion in Pancreatic and Lung Cancer
Potential Market Expansion Opportunities in First - line Metastatic Pancreatic Cancer and Advanced Lung Cancer Avutometinib ± Defactinib
Slide 29: Topline Data from RAMP 205 in First-Line Metastatic Pancreatic Cancer
29 Topline Data from RAMP 205: Avutometinib + Defactinib + SOC in First - Line Metastatic Pancreatic Cancer
Slide 30: RAMP 205 Trial Design
30 DLT: dose - limiting toxicity; n: number of patients; ORR: overall response rate; RP2D: recommended phase 2 dose; CT: computed tom ography; ECOG: European Cooperative Oncology Group; MRI: magnetic resonance imaging RAMP 205: Designed to Identify and Evaluate RP2D in C ombination with Chemotherapy
Slide 31: RAMP 205 Updated Interim Safety and Efficacy
31 *On track to complete enrollment in Q1 2025. DLT: dose - limiting toxicity; ASCO: American Society of Clinical Oncology RAMP 205: Updated Initial Interim Safety and Efficacy Results # Patients Nab - Pac Gem Defactinib Avuto Dose Level Day 1, 8, 15 chemo dosing: 12 100 mg/m 2 800 mg/m 2 200 mg BID
Slide 32: Landmark Trials in First-Line Metastatic Pancreatic Cancer
32 For Reference only: No cross - trial comparison made.*Dosing schedule in Gem/ NabP arms above= 1000/125 ሺ ‰ Ȁ ଶ ) D1,8,15 q 4w, **Secondary endpoint of ORR based on IRR (Independent Radiology Review), • SOC Treatment Landscape: • ORR is between 23% - 36% for Gem/ NabP • Median overall survival
Slide 33: RAMP 205 Multiple Regimens Evaluated in Parallel
33 Data Cutoff Date:14 MAY 2024 RAMP 205: Evaluating Multiple Regimens in Parallel to Efficiently Identify RP2D in First - Line mPDAC Nab - Pac Gem Defactinib Avuto Dose Level Day 1, 8, 15 chemo dosing: 100 mg/m 2 800 mg/m 2 200 mg BID 2.4 mg BIW - 1 125 mg/m 2 800 mg/m 2 200 mg BID 2.4 mg BIW 1 Day
Slide 34: RAMP 205 AE Profile
34 No head - to - head clinical trials have been conducted between avutometinib and defactinib combination and gemcitabine and Nab - pacl itaxel. e1. Lim t al. ASCO 2024 Abstract #4140; Data Cutoff: May 14, 2024, TEAEs were graded based on guidelines provided in CTCAE v5 .0. CTCAE v5.0, Common Termi
Slide 35: Next Steps for RAMP 205
35 Next Steps for RAMP 205 Plan to present additional data at a medical meeting in mid - year 2025 Select the RP2D for trial expansion in H1 2025
Slide 36: Avutometinib ± Defactinib with Sotorasib in KRAS G12C NSCLC
Avutometinib ± Defactinib with Sotorasib (G12Ci) in KRAS G12C mutant NSCLC 36
Slide 37: FAK Inhibitor Augments Sotorasib + Avutometinib in Preclinical Models
37 Collaboration Verastem & Mariano Barbacid , CNIO (Spain) Addition of FAK inhibitor Augments the Efficacy of Sotorasib + Avutometinib and Reverses Sotorasib Resistance in KRAS G12C NSCLC Preclinical Models AVUTOMETINIB ENHANCES SOTORASIB EFFICACY. ADDITION OF FAK INHIBITOR INDUCES DEEP TUMOR REGRE
Slide 38: RAMP 203 Phase 1/2 Trial Design
38 Collaboration with Amgen, NCT05074810 DLT, dose - limiting toxicity; KRAS, kristen rat sarcoma virus; NSCLC, non - small cell lung cancer; ORR, objective response rate; RECIST v1.1, response evaluation criteria i n solid tumours version 1.1; RP2D, recommended phase 2 dose. RAMP 203: Phase 1/2 Tri
Slide 39: RAMP 203 No DLTs in First Triplet Cohort
39 RAMP 203: No DLTs Were Observed in the First Triplet Combination Cohort in Patients Previously Treated with a G12C Inhibitor Triplet Combination Update: • As of a November 21, 2024 , data cutoff, 3 patients whose cancer previously progressed on a G12C inhibitor have been treated with the triplet
Slide 40: Next Steps for RAMP 203
40 Next Steps for RAMP 203 Plan to present an interim update of both doublet and triplet data at a medical meeting in H2 2025
Slide 41: Partnership with GenFleet Therapeutics
Partnership with GenFleet Therapeutics on Novel, Potential Best - in - Class RAS Pathway - Related Programs 41
Slide 42: KRAS G12D is the Most Frequent KRAS Mutation in Human Cancers
42 Adapted from Hofmann et al., Cancer Discovery 2022 • The only approved KRAS inhibitors target KRAS G12C which is largely restricted to NSCLC • KRAS G12D accounts for 26% of all KRAS mutations • KRAS G12D mutations are especially prevalent in pancreatic and colorectal cancers • Targeting KRAS G12D
Slide 43: VS-7375 is an Oral KRAS G12D (ON/OFF) Inhibitor
43 *Piro Lito, RAS Initiative Conference 2024; GEF: Guanine nucleotide exchange factor; GAP: GTPase - activating protein; *Zhou et al ., AACR 2024 VS - 7375 is an Oral KRAS G12D (ON/OFF) Inhibitor GEF GTP GDP GTP GDP RAS/MAPK pathway signaling GAP P KRAS OFF (inactive) KRAS ON (active) VS - 7375 KRA
Slide 44: VS-7375 Induces Tumor Regression in KRAS G12D Models
44 Source for all data: Zhou et al., AACR 2024 VS - 7375 Induces Tumor Regression in Multiple KRAS G12D Tumor Models via Oral Administration AsPC - 1 PDAC Panc 04.03 PDAC LS513 CRC GP2D CRC 0 2 4 6 8 10 12 14 16 0 200 400 600 800 1000 Days after first dose T u m o r v o l u m e ( m m 3 , m e a n ± S
Slide 45: VS-7375 Preclinical Properties vs Other KRAS G12D Inhibitors
45 NR: not reported ; PO = oral administration; IP = intraperitoneal admiration; BID = twice per day; QD = once per day; QW = on ce per week; BIW = twice per weekReferences : GenFleet / Verastem AACR 2024; Hallin et al (Mirati) 2022; RevMed AACR 2023; RevMed AACR 2024; Lilly ENA 2023; Lilly AACR 202
Slide 46: VS-7375 Initial Oral Bioavailability and Clinical Activity
46 VS - 7375: Initial Data Demonstrate Oral Bioavailability and Clinical Activity • 26 patients have been treated with VS - 7375 in a Phase 1 dose escalation study being conducted in China 1 • Both confirmed and unconfirmed partial responses have been observed , including multiple patients with meta
Slide 47: Next Steps in G12D Program
47 Next Steps in G12D Program GenFleet plans to continue to enroll patients into Phase 2 trial for VS - 7375/ GFH375 in China in patients with KRAS G12D - mutated advanced solid tumors Verastem/GenFleet expect to share updated preclinical and clinical data at medical meetings in H1 2025 Filed U.S. I
Slide 48: Anticipated Milestones & Financials
48 Anticipated Milestones & Financials 48
Slide 49: Planned Near-Term LGSOC Commercial Launch and Catalysts
49 Planned Near - Term LGSOC Commercial Launch, Followed by Meaningful Catalysts to Expand Into Larger, Underserved Patient Populations Anticipated Milestones & Activities Program x Present additional analyses from the RAMP 201 trial at a medical meeting in Q1 2025 □ Plan for June 30, 2025 PDUFA act
Slide 50: Cash Position and Financial Summary
50 *Cash, cash equivalents, & short - term investments of $88.8M as of December 31, 2024, plus proceeds of $32.3M in January 2025 fro m Oberland Finance credit facility after repayment of Oxford facility, equity purchase from Oberland Finance of $7.5M in January 2025, and $22.7M equity issuance. Bot
Slide 51: Thank You
THANK YOU! 51
Slide 52: Addendum
Addendum VW VERASTEM V oncotocy
Slide 53: Avutometinib Patent Exclusivity
53 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 54: Experienced Senior Management Team
54 Experienced Senior Management Team Cathy Carew Chief Organizationa l Effectiveness Officer Colleen Mockbee Global Head of Regulatory Affairs and Development Nate Sanburn Chief Business Officer Dan Calkins Chief Financial Officer Matt Ros Chief Operating Officer Mike Crowther Chief Commercial & St
Slide 55: Optimized Dosing Schedule with Intermittent Dosing Regimen
55 Optimized Dosing Schedule Defined: Favorable Tolerability Profile with Novel Intermittent Dosing Regimen RP2D (Avutometinib 3.2mg twice weekly + defactinib 200mg twice daily) N=38 21 days of 28 - day cycle RP2D Avutometinib monotherapy 4mg twice weekly N=26 28 - day cycle Avutometinib monotherapy
Slide 56: FDA Breakthrough Therapy Designation Based on FRAME Data
56 Breakthrough Through Therapy Designation for combination of avutometinib and defactinib for treatment of recurrent LGSOC after one or more prior lines of therapy including platinum - based chemotherapy *Denis, 5th Annual RAS - Targeted Drug Development Sept 2023; (Data cut off July 2023: Data on
Slide 57: References
57 1 Monk, Randall, Grisham, The Evolving Landscape of Chemotherapy in Newly Diagnosed Advanced Epithelial Ovarian Cancer, Am Soc Cl in Oncol Educ Book; 2019; Slomovitz , Gourley, Carey, Malpica, Shih, Huntsman, Fader., Grisham et al, Low - Grade serous ovarian cancer: State of the Science; Gynecol