Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Presentation (September 2025)
55 slides from Verastem's investor presentation, Sep 8, 2025
Slide 1: Delivering Novel Therapies for RAS/MAPK Pathway Driven Cancers
Delivering Novel Therapies for RAS/MAPK Pathway Driven Cancers Corporate Presentation | September 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 approval and commercialization of AVMAPKI
Slide 3: Commercial Product and Pipeline Positioned to Deliver Long-Term Shareholder Value
3 3 Commercial Product and Pipeline Positioned to Deliver Long - Term Shareholder Value • Strong early execution of commercial launch • May 2025 approval of AVMAPKI FAKZYNJA CO - PACK, six weeks ahead of PDUFA action date • First - ever FDA - approved treatment specifically f or KRAS - mutated recur
Slide 4: AVMAPKI FAKZYNJA CO-PACK Commercial Launch is Off to a Strong Start
4 AVMAPKI FAKZYNJA CO - PACK Commercial Launch is Off to a Strong Start FDA Approved on May 8, 2025, Nearly Two Months Ahead of PDUFA action date RAS/MAPK Pathway Directed MOA • AVMAPKI offers dual inhibition of RAF and MEK • FAKZYNJA mediates drug resistance of activated RAF/MEK • Together, they of
Slide 5: Anticipated Milestones
5 Anticipated Milestones FDA Approved Phase 3 Phase 2 Phase 1 Regimen Trial Name/ Therapeutic Area Asset RAF/MEK Clamp + FAKi RAMP 201, recurrent LGSOC Avutometinib + Defactinib Complete planned enrollment in RAMP 301 by the end of 2025; Report IDMC outcome in Q4 2025 RAF/MEK Clamp + FAKi vs ICT RAM
Slide 6: Delivering on the Key R&D Milestones Set for 2025
6 x Reported updated data from the ongoing RAMP 205 trial and s elected dose level 1 cohort for recommended phase 2 dose (RP2D) x Close to completing enrollment in the expansion cohort of 29 patients at the RP2D RAMP 205: Avutometinib + Defactinib + SOC Chemotherapy in 1L mPDAC x Completed enrollmen
Slide 7: Achieved All Key Milestones in 1H25, On Track To Deliver in 2H25
7 Achieved All Key Milestones in 1H25, On Track To Deliver in 2H25 RAMP 301 Complete planned enrollment in the Phase 3 confirmatory study by the end of 2025. Report IDMC recommendation in Q4 2025. RAMP 201J Report initial data from Phase 2 clinical trial being conducted in Japan in Q4 2025. RAMP 203
Slide 8: Commercially launched in the U.S. for KRAS-mutated Recurrent LGSOC
8 Commercially launched in the U.S. for KRAS - mutated Recurrent LGSOC FDA Approval Date: May 8, 2025
Slide 9: More Complete Blockade of Signaling that Drives Growth and Resistance of RAS/MAPK Tumors
9 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 ;
Slide 10: High Unmet Need for an Effective and Tolerable Therapy in Recurrent LGSOC
10 High Unmet Need for an Effective and Tolerable Therapy in Recurrent LGSOC • U.S. incidence / prevalence : 1k - 2k 1 / 6k - 8k 2 • LGSOC affects younger women with bimodal peaks of diagnosis at ages between 20 - 30 and 50 - 60; disproportionately impacts health, fertility, and long - term quality
Slide 11: Three Strategic Imperatives to Drive a Successful Commercial Launch
11 Laser - Focused on Three Strategic Imperatives to Drive a Successful Commercial Launch Effectively reach all healthcare providers Engage and support patients Ensure seamless access Top 100 commercial healthcare organizations contribute ~50% of patient claims 1 Patients likely to have progressed t
Slide 12: Encouraging Launch Momentum Reinforces Strategic Imperatives
12 Encouraging Launch Momentum Reinforces Strategic Imperatives to Drive Success Achieved net product revenue of $2.1 million in the first six weeks on the market First patient received product: May 22, 2025 x First - ever approved treatment specifically for people living with KRAS - mutated recurre
Slide 13: Early Launch Performance Tracking as Expected
13 Early Launch Performance Tracking as Expected x Prescriptions coming from a mix of academic and community physicians x Seeing both repeat prescriptions and refills x Payer mix is a combination of commercial and Medicare Effectively reach all healthcare providers Engage and support patients Ensure
Slide 14: NCCN Submission for Treatment Guideline Inclusion Under Review
14 NCCN Submission for Treatment Guideline Inclusion Under Review for the Entire Population Enrolled in RAMP 201 Study NCCN Category 3 NCCN Category 2b NCCN Category 2a NCCN Category 1 General % Commercial Payer Coverage Binimetinib • Study stopped early due to futility • 16% ORR byBICR • 31% discon
Slide 15: Continuing Medical Progress in LGSOC
15 Continuing Medical Progress in LGSOC
Slide 16: 82% Had a Reduction in Target Lesions in RAMP 201
16 Across Patients With and Without KRAS Mutations in RAMP 201, 82% had a Reduction in Target Lesions while Receiving Avutometinib and Defactinib Source for all data: RAMP 201 data cut off as of June 30, 2024; Responses for 3 patients (KRAS wild type, n=1; KRAS mutant, n =2) were unknown Best Overal
Slide 17: RAMP 301: Phase 3 Confirmatory Trial in Recurrent LGSOC
17 *US FDA analysis plan will evaluate PFS independently in KRAS - mt and KRAS wt LGSOC. 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:
Slide 18: Next Steps in LGSOC Clinical Program
18 Next Steps in LGSOC Clinical Program Report initial data from the RAMP 201J Phase 2 clinical trial being conducted in Japan in Q4 2025 Complete planned enrollment in RAMP 301 Phase 3 confirmatory study by end of 2025 Continue to advance regulatory pathway in Japan and Europe Announce outcome of I
Slide 19: VS-7375, oral KRAS G12D (ON/OFF) Inhibitor
VS - 7375, oral KRAS G12D (ON/OFF) Inhibitor 19
Slide 20: KRAS G12D is the Most Frequent KRAS Mutation in Human Cancers
20 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 G12
Slide 21: VS-7375 is an Oral KRAS G12D (ON/OFF) Inhibitor
21 *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 VS - 7375 IC50 ( nM ) (KRAS G12D binding) KRAS G12D State 2 1 GppNHp - bound (ON/active) 6 1 GDP - boun
Slide 22: VS-7375 More Efficacious than G12D ON and pan-RAS ON Inhibitors in Models
22 VS - 7375 (G12D ON/OFF inhibitor) is more efficacious than G12D ON and pan - RAS ON inhibitors in KRAS G12D mutant tumor models KP4 Pancreatic Cancer Model LU0876 NSCLC PDX Model -100 0 100 200 500 1000 1500 2000 R e s p o n s e @ D a y 2 0 ( % c h a n g e f r o m b a s e l i n e ) v e h i c l e
Slide 23: GFH375 Demonstrated Encouraging Initial Efficacy in Lung and Pancreatic Cancers
23 GFH375 Demonstrated Encouraging Initial Efficacy in Lung and Pancreatic Cancers Source: GenFleet Therapeutics ASCO 2025 Rapid Oral Presentation June 2, 2025; A First - in - human Phase I/II Study of GFH375, a Highly Selective an d Potent Oral KRAS G12D Inhibitor in Patients in KRAS G12D Mutant Ad
Slide 24: Duration of Treatment and Tumor Assessment of All Patients
24 Duration of Treatment and Tumor Assessment of All Patients Month Data cut - off date: 16 May 2025 All patients received first dose of GFH375 at least 10 weeks prior to data cutoff date. The y - axis tick label is tumor type and number of prior lines of therapies. Abbreviations: NE, not evaluable;
Slide 25: GFH375 WCLC 2025: NSCLC Patient Characteristics
25 Source: GenFleet Therapeutics WCLC 2025 Mini Oral Presentation September 7. 2025; Efficacy and Safety of GFH375 in Advanced N on - Small Cell Lung Cancer Patients with KRAS G12D Mutation. WCLC 2025 Cut - off date: 01 August 2025. NSCLC at 600 mg QD (n=16) All NSCLC (n=28) 4 (25.0) 12 (42.9) Disco
Slide 26: GFH375 WCLC 2025: Efficacy in NSCLC
26 Source: GenFleet Therapeutics WCLC 2025 Mini Oral Presentation September 7. 2025; Efficacy and Safety of GFH375 in Advanced N on - Small Cell Lung Cancer Patients with KRAS G12D Mutation. WCLC 2025 600mg QD (N=16) All patients (N=26) 68.8% [41.3%, 89.0%] 57.7% [39.8%, 74.2%] ORR [90% CI] 93.8% [6
Slide 27: WCLC 2025 GFH375: Safety in All Patients
27 WCLC 2025 GFH375: Safety in All Patients Source: GenFleet Therapeutics WCLC 2025 Mini Oral Presentation September 7. 2025; Efficacy and Safety of GFH375 in Advanced N on - Small Cell Lung Cancer Patients with KRAS G12D Mutation. • 142 patients, including 28 NSCLC, with advanced KRAS G12D mutation
Slide 28: GFH375: Safety in All Patients
28 WCLC 2025 Source: GenFleet Therapeutics WCLC 2025 Mini Oral Presentation September 7. 2025; Efficacy and Safety of GFH375 in Advanced N on - Small Cell Lung Cancer Patients with KRAS G12D Mutation. GFH375: Safety in All Patients • No new safety signals were observed. • The most frequent TRAEs wer
Slide 29: VS-7375 Study Schema
29 VS - 7375 - 101 Study Schema, Efficiently Testing KRAS G12D+ Indications with Monotherapy and SOC Combinations Part A: Single Agent Dose Escalation – Any KRAS G12D Solid Tumor Cohort B1: 2L+ PDAC (N=20) Cohort D1: 2L+ CRC Cetuximab (N=20) VS - 7375 + Combinations Part B: Dose Expansion Part C: Co
Slide 30: Accelerated Development Approach Builds on Preliminary First-in-Human Findings
30 • Efficacious starting dose: • 400 mg starting dose supported by monotherapy efficacy/safety in FIH study • Evaluating GI side effect mitigations: • Use prophylactic anti - emetics • Evaluate dosing with and without food • Evaluate additional formulation • Multiple, high - value indication strate
Slide 31: Next Steps in VS-7375 Clinical Program
31 Next Steps in VS - 7375 Clinical Program Expect to report a preliminary update on the Phase 1 monotherapy dose escalation in Q4 2025. ௗ Subject to the results of the Phase 1 monotherapy dose escalation, initiate monotherapy expansion cohorts in PDAC, NSCLC, and other solid tumors. Initiate the do
Slide 32: Topline Data from RAMP 205 in First-Line Metastatic Pancreatic Cancer
Topline Data from RAMP 205: Avutometinib + Defactinib + Standard of Care in First - Line Metastatic Pancreatic Cancer
Slide 33: PDAC Represents an Area of High Unmet Need
33 1 SEER 12; 2 worldometers; 3 Globocan/Japan/factsheet; 4 McIntyre, Cancer Cell, Sept 2023; 5 Yu, Frontiers in Oncology, Jul 2021 Pancreatic Ductal Adenocarcinoma (PDAC) Represents an Area of High Unmet Need 0 5 10 15 20 25 30 35 40 45 50 5-Yr Relative Survival KRAS Mutations Are Present in ~90 -
Slide 34: RAMP 205: Designed to Identify RP2D in Combination with Chemotherapy
34 DLT: dose - limiting toxicity; RP2D: recommended phase 2 dose; CT: computed tomography; ECOG: European Cooperative Oncology Group; MRI: magnetic resonance imaging RAMP 205: Designed to Identify and Evaluate RP2D in Combination with Chemotherapy for Treatment of Newly Diagnosed mPDAC RAMP 205: Ong
Slide 35: RAMP 205: 12 Patients Enrolled in Each Dose Cohort
35 Updated 05/01/25 Enrolled N=60 Days Chemo Dosing Nab - Paclitaxel Gemcitabine Defactinib Avutometinib Dose Level 12 1 - 8 - 15 125 800 200 2.4 1 12 1 - 8 - 15 100 800 200 3.2 0 12 1 - 8 - 15 100 800 200 2.4 - 1 12 1 - 15 125 800 200 3.2 1a 12 1 - 15 125 1000 200 3.2 2a PART A Enrollment Summary D
Slide 36: Dose Level 1 Demonstrated a Confirmed 83% ORR
36 Source: F_TR_WATERFALL.sas Data Cut: 01 AUG 25 Dose Level 1 Demonstrated a Confirmed 83% ORR with Tumor Shrinkage Observed in All Patients Dose Level 1: Response & Disease Control Rate as of August 1, 2025 83.3% ( 10/12) Confirmed ORR, n (%) 10 (83.3) PR, n (%) 2 (16.7) SD, n (%) 0 PD, n (%) 92%
Slide 37: Encouraging Duration of Treatment Observed for Dose Level 1
37 Source: Program:F_TX_RS_SWIMMER_DL1.sas Data Cut: 25 APR 25 Encouraging Duration of Treatment Observed to Date for Dose Level 1 Dose Level 1 Duration of Treatment Safety Population (n=12) Historical Gem/Nab PFS 95% CI mPFS Reference Study 4.5 - 5.9 5.5 MPACT N=421 Von Hoff 2013 5.3 - 5.8 5.6 NAPO
Slide 38: Patient with mPDAC Showed Substantial Tumor Shrinkage in Dose Level 1
38 Source: Dr. Lim, Siteman Cancer Center 7 Patient with mPDAC Showed Substantial Tumor Shrinkage in Dose Level 1 Before C1 After C2 After C4 After C6 metastasis primary tumor 63 year - old Female
Slide 39: AEs were Generally Manageable, Allowing Patients to Remain on Treatment
39 AEs were Generally Manageable, Allowing Patients to Remain on Treatment DL1 Treatment Emergent AE All Grades ≥ 25% / Non - laboratory AEs NAPOLI 3* (N=379) Dose Level 1 (n=12) TEAEs Grade ≥3 n (%) All Grades n (%) Grade ≥3 n (%) All Grades n (%) Preferred term 10 (3) 162 (43) 0 10 (83) Nausea 17
Slide 40: Next Steps for RAMP
40 Next Steps for RAMP 205 Complete enrollment up to 29 patients in RAMP 205 at the RP2D in Q3 2025
Slide 41: Avutometinib ± Defactinib with Sotorasib in KRAS G12C mutant NSCLC
Avutometinib ± Defactinib with Sotorasib (G12Ci) in KRAS G12C mutant NSCLC
Slide 42: Addition of FAK Inhibitor Augments Efficacy of Sotorasib + Avutometinib
42 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 43: RAMP 203: Phase 1/2 Trial of Avutometinib + Sotorasib ± Defactinib
43 Collaboration with Amgen, NCT05074810 DRECIST v1.1, response evaluation criteria in solid tumours version 1.1 RAMP 203: Phase 1/2 Trial of Avutometinib + LUMAKRAS TM (Sotorasib) Defactinib in KRAS G12C Advanced NSCLC Inclusion Criteria • Documented KRAS G12C mutation determined using validated te
Slide 44: RAMP 203: No DLTs Observed in First Triplet Combination Cohort
44 RAMP 203: No Dose - Limiting Toxicities (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, three patients whose cancer previously progressed on a G12C inhibitor hav
Slide 45: Next Steps for RAMP
45 Next Steps for RAMP 203 Report an interim update on the efficacy and safety results from both the doublet and triplet combinations in Q4 2025
Slide 46: Anticipated Milestones & Financials
46 Anticipated Milestones & Financials 46
Slide 47: Execute Successful Commercial Launch in LGSOC, Followed by Meaningful Catalysts
47 Execute Successful Commercial Launch in LGSOC, Followed by Meaningful Catalysts to Expand Into Larger, Underserved Patient Populations Anticipated Milestones & Activities in 2H 2025 Program □ Complete planned enrollment in RAMP 301 by end of 2025 □ Announce outcome of IDMC’s sample - size re - es
Slide 48: Key Financial Statistics
48 *Q2 2025 GAAP operating expenses of $45.90M less Q2 2025 stock - based compensation expense of $3.41M = $42.49M Q1 2025 non - GAAP o perating expenses. **Excludes unexercised warrants (14.1M shares upon exercise) and unexercised pre - funded warrants (9.8M shares upon exercise) . Key Financial St
Slide 49: Thank You!
THANK YOU! ONCOLOGY W VERASTEM
Slide 50: AVMAPKI FAKZYNJA CO-PACK Patent Portfolio
50 OB: Orange Book Listed Patent AVMAPKI FAKZYNJA CO - PACK Patent Portfolio OB: 7,897,792 Avutometinib COM (expiry 2/9/2027) OB: 11,400,090 – Avutometinib mono dosing - (expiry 10/29/2038) PTE OB: 7,928,109 Defactinib COM US (expiry 4/17/2028) PTA PTE (Aug, 2034) OB: 8,247,411 Defactinib – genus (e
Slide 51: Experienced Senior Management Team
51 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 52: Oral VS-7375 Inhibits Tumor Growth in a Dose-Dependent Manner in KRAS G12D Models
52 Oral Administration of VS - 7375 Inhibits Tumor Growth in a Dose - Dependent Manner in KRAS G12D models AsPC - 1 PDAC Panc 04.03 PDAC GP2D CRC LS513 CRC -100 -50 0 50 100 150 200 250 300 350 R e s p o n s e @ D a y 1 4 ( % c h a n g e f r o m b a s e l i n e ) v e h i c l e V S - 7 3 7 5 1 0 m g
Slide 53: Dose Levels Achieved Steady State Target Exposures in Almost All Patients
53 Dose Levels of 400 and 600 mg QD Achieved Steady State Target Exposures in Almost all Patients Human equivalent to 100 mg/kg in mice (PR in all mice in all models) Human equivalent to 30 mg/kg in mice (Tumor regressions in all models) Human equivalent to 10 mg/kg in mice (Tumor regressions in mos
Slide 54: Cetuximab with VS-7375 Induces Complete Responses in KRAS G12D CRC Model
54 Addition of Cetuximab with VS - 7375 Induces Complete Responses in All Mice in a KRAS G12D Colorectal Cancer Model LS513 Colorectal Cancer Model 0 10 20 30 40 0 500 1000 1500 Tumor growth Days after first dose T u m o r v o l u m e ( m m 3 + / - S E M ) Vehicle GFH375 Cetuximab GFH375 + cetuximab
Slide 55: VS-7375 Shows Potential Best-in-Class Preclinical Properties
55 NR: not reported; IP: intraperitoneal admiration; QD; once per day; QW; once per week; References: GenFleet /Verastem AACR 2024; Hallin et al (Mirati) 2022; RevMed AACR 2023; RevMed AACR 2024; Lilly ENA 2023; Lilly AACR 2024; AstraZeneca (AZ) AACR 2024; Incyte AACR 2024; Quanta AACR 2023; Tyligan