Verastem, Inc. · NASDAQ:VSTM
Verastem — Investor Day (June 2025)
39 slides from Verastem's investor day presentation, Jun 2, 2025
Slide 1: Verastem Oncology R&D Investor Event ASCO 2025
Verastem Oncology R&D Investor Event ASCO 2025 June 2, 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: Agenda
3 3 Agenda Dan Paterson, President & CEO Welcome & Overview Vincent Picozzi, M.D. Pancreatic Cancer Treatment Landscape & RAMP 205 Data Update Jon Pachter, Ph.D., CSO VS - 7375: KRAS G12D (ON/OFF) Inhibitor with a Differentiated Preclinical Profile David Hong, M.D. Review of VS - 7375 US Phase 1/2a
Slide 4: Welcome & Overview
4 Daniel Paterson President & CEO Welcome & Overview
Slide 5: Multi-faceted Approach to Improve Outcomes in RAS/MAPK Pathway Driven Cancers
5 Verastem Oncology: Multi - faceted Approach to Improve Outcomes in RAS/MAPK Pathway Driven Cancers Pursuing unexplored avenues in the RAS/MAPK pathway with novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth. • Address ca
Slide 6: AVMAPKI FAKZYNJA CO-PACK is the First and Only FDA-Approved Treatment for KRAS-Mutated Recurrent LGSOC
6 AVMAPKI FAKZYNJA CO - PACK is the First and Only FDA - Approved Treatment for KRAS - Mutated Recurrent LGSOC FDA Approved on May 8, 2025 RAS/MAPK Pathway Directed MOA • AVMAPKI offers dual inhibition of RAF and MEK • FAKZYNJA mediates drug resistance of activated RAF/MEK • Together, they offer a m
Slide 7: Pancreatic Cancer Treatment Landscape & RAMP 205 Data Update
Pancreatic Cancer Treatment Landscape & RAMP 205 Data Update Pancreatic Cancer Treatment Landscape & RAMP 205 Data Update Vincent J. Picozzi, M.D. Director for the Pancreaticobiliary Program at the Virginia Mason Medical Center Investigator for RAMP 205 and VS - 7375 - 101 clinical trials
Slide 8: Pancreatic Ductal Adenocarcinoma Represents an Area of High Unmet Need
8 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 - 9
Slide 9: Locally Advanced and Metastatic PDAC: 1L and 2L+ Treatment Paradigm
9 Locally Advanced and Metastatic PDAC: 1L and 2L+ Treatment Paradigm Locally Advanced (LA)/Metastatic PDAC (50 - 60% 2 will recur with LA/Metastatic disease) ~40 - 50% 1 local/regional disease at diagnosis ~50 - 60% 1 metastatic disease at diagnosis 1 SEER 21 (2015 - 20210), 2 Jones, JAMA Surg. Sep
Slide 10: More Complete Blockade of Signaling Driving Growth and Resistance of RAS/MAPK Pathway
10 More Complete Blockade of the Signaling that Drives Growth and Resistance of RAS/MAPK Pathway - Dependent Tumors RAF - MEK Complex Inhibited FAK The Combination of Avutometinib and Defactinib Induces Deeper Inhibition of Tumor Growth • Avutometinib inhibits MEK kinase activity while blocking the
Slide 11: FAK Inhibitor Reduces Pancreatic Cancer Stromal Density
11 1) Jiang H et al., Nature Med 22 : 851, 2016; 2) Wang - Gillam A et al., Clin Cancer Res 28 : 5254, 2022 FAK inhibitor ( Defactinib ) Reduces Pancreatic Cancer Stromal Density Preclinically and Clinically FAKi reduced stromal density in a preclinical (KPC) pancreatic cancer model 1 Defactinib + g
Slide 12: Avutometinib + FAKi with Chemotherapy Induces Tumor Regression in Mouse Model
12 Liu X et al., Sci Transl Med 2024; GEM: gemcitabine, PTX: paclitaxel Addition of Avutometinib + FAKi with Chemotherapy Induces Tumor Regression, and Decreases Liver Metastases in a KRAS/p53 Pancreatic Cancer Mouse Model vehicle avutometinib/ FAKi gemcitabine/paclitaxel avutometinib / FAKi + gemci
Slide 13: RAMP 205: Designed to Identify and Evaluate RP2D in Combination with Chemotherapy
13 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 Ongoing Phase
Slide 14: RAMP 205: 12 Patients Enrolled in Each Dose Cohort
14 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 15: Dose Level 1 Demonstrated an 83% ORR
15 Source: F_TR_WATERFALL.sas Data Cut: 25 APR 25 Dose Level 1 Demonstrated an 83% ORR with Tumor Shrinkage Observed in All Patients Dose Level 1: Efficacy Evaluable Population (n=12) Dose Level 1: Response & Disease Control Rate as of April 25, 2025 83.3% ( 10/12) Unconfirmed ORR, n (%) 66.7% (8/12
Slide 16: Encouraging Duration of Treatment Observed for Dose Level 1
16 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 17: AEs were Generally Manageable, Allowing Patients to Remain on Treatment
17 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 18: Tumor Reduction Across All Dose Cohorts
18 Source: F_TR_WATERFALL.sas Data Cut: 25 APR 25 2 patients excluded from efficacy evaluable population due to no post baseline scan. Change from baseline at each visit is ca lcu lated for the lesions that were measured at both baseline and post - baseline visit. One patient in DL1 came off study t
Slide 19: Duration of Treatment for All Patients
19 Duration of Treatment for All Patients: Safety Population (N=60) Response assessment after first PD are not shown. Note: Subject 0151 - 008 came off study treatment in Cycle 3, but continued to receive Nab - paclitaxel and gemcitabine and is count ed in the efficacy population Source: Program: F_
Slide 20: Conclusions
20 • Impressive efficacy signals and a manageable safety profile • Dose level 1 selected as the RP2D • 10/12 patients in dose level 1 achieved an objective response • Preliminary observations suggest increased Nab - paclitaxel dose intensity, along with optimizing avutometinib, defactinib, and gemci
Slide 21: VS-7375: KRAS G12D (ON/OFF) Inhibitor with a Differentiated Preclinical Profile
21 Jonathan Pachter, PhD Chief Scientific Officer VS - 7375: KRAS G12D (ON/OFF) Inhibitor with a Differentiated Preclinical Profile
Slide 22: VS-7375 is an Oral KRAS G12D (ON/OFF) Inhibitor
22 *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 23: VS-7375 Shows Improved KRAS G12D Selectivity and Potency vs Other Inhibitors
23 MRTX1133 IC50 (nM) RMC - 9805 IC50 (nM) VS - 7375 IC50 (nM) KRAS status Cell Line 414 7 8 G12D SKLU1 187 4 2 G12D KP4 >5000 8 2 G12D GP2D 156 9 7 G12D HPAC 124 18 5 G12D HPAF - II 248 19 7 G12D AsPC1 739 26 8 G12D Panc08.13 265 28 7 G12D LS513 >5000 96 33 G12D LS180 1332 111 63 G12D Panc04.03 105
Slide 24: VS-7375 More Efficacious than KRAS ON Inhibitors in Reducing Tumor Growth
24 VS - 7375 (G12D ON/OFF inhibitor) is More Efficacious than KRAS ON Inhibitors in Reducing Tumor Growth in KRAS G12D Models KP4 KRAS G12D PDAC model LS513 KRAS G12D CRC model 0 10 20 30 40 0 500 1000 1500 Days after first dose T u m o r v o l u m e ( m m 3 + / - S E M ) Vehicle RMC-6236 25 mg/kg Q
Slide 25: Oral VS-7375 Inhibits Tumor Growth in a Dose-Dependent Manner
25 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 26: Cetuximab with VS-7375 Induces Complete Responses in Colorectal Model
26 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 27: Review of VS-7375 US Phase 1/2a Trial and Supportive Data
David S. Hong, MD Douglas E. Johnson Endowed Professor Deputy Chair of the Department of Investigational Cancer Therapeutics [A Phase I Program] Division of Cancer Medicine Clinical Medical Director of the Clinical and Translational Research Center (CTRC) University of Texas M.D. Anderson Cancer Cen
Slide 28: KRAS G12D is the Most Frequent KRAS Mutation in Human Cancers
28 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 29: GFH375 Demonstrated Encouraging Initial Efficacy in Lung and Pancreatic Cancers
29 Source: GenFleet Therapeutics ASCO 2025 Rapid Oral Presentation June 2, 2025; A First - in - human Phase I/II Study of GFH375, a Hig hly Selective and Potent Oral KRAS G12D Inhibitor in Patients in KRAS G12D Mutant Advanced Solid Tumors GFH375 Demonstrated Encouraging Initial Efficacy in Lung and
Slide 30: Initial AE Profile Shows GFH375 is Tolerable
30 Initial AE Profile Demonstrates that GFH375 is Tolerable with a Manageable Safety Profile Source: GenFleet Therapeutics ASCO 2025 Rapid Oral Presentation June 2, 2025; A First - in - human Phase I/II Study of GFH375, a Hig hly Selective and Potent Oral KRAS G12D Inhibitor in Patients in KRAS G12D
Slide 31: Once Daily Dosing Achieves Trough Concentrations 3x the IC90
31 Convenient Once Daily Dosing Achieves Trough Concentrations 3x the IC 90 for pERK inhibition in KRAS G12D cell lines Source: GenFleet Therapeutics ASCO 2025 Rapid Oral Presentation June 2, 2025; A First - in - human Phase I/II Study of GFH375, a Hig hly Selective and Potent Oral KRAS G12D Inhibit
Slide 32: Verastem Phase 1/2a Study Design
32 Verastem Phase 1/2a Study Includes Monotherapy Expansion Cohorts in PDAC and NSCLC and Cetuximab Combination in CRC Part A: Single Agent Dose Escalation – Any KRAS G12D Solid Tumor VS - 7375 Single Agent: Advanced solid tumors Cohort B1 (N=20) 2L+ PDAC Cohort D1 (N=20) 2L+ CRC w/ Cetuximab VS - 7
Slide 33: Conclusions
33 Conclusions • With promising early results, VS - 7375 has the potential to meet a significant unmet need in solid tumor cancers o The unmet need is high: 61,000 metastatic KRAS G12D patients are diagnosed every year across pancreatic, lung, colorectal and other solid tumor cancers • In the initia
Slide 34: Clinical Development Plans and Timelines
John Hayslip, MD Chief Medical Officer Clinical Development Plans and Timelines
Slide 35: Opportunity for Avutometinib Plus Defactinib in Advanced Pancreatic Cancer
35 Opportunity for Avutometinib Plus Defactinib with SOC Chemo to Reshape Expectations in Advanced Pancreatic Cancer • Our Opportunity: • A novel regimen for metastatic PDAC, with most patients achieving objective responses • Target Product Profile: Clinical Focus: • Phase 2 RAMP 205 IL mPDAC • Expa
Slide 36: Emerging VS-7375 Clinical Findings and Planned Next Steps
36 • Our Opportunity: • Target Product Profile: • Once - daily oral administration • Highly potent and selective for KRAS G12D with binding to ON/OFF states • Efficacy: potential for best - in - class response rates and durability • Safety: MTD not yet declared and potential to further improve the G
Slide 37: Closing Remarks
37 Closing Remarks Daniel Paterson President & CEO
Slide 38: Delivering on Our Multi-Faceted Approach for RAS/MAPK Pathway Driven Cancers
38 Delivering on Our Multi - Faceted Approach to Advance Novel Therapies for RAS/MAPK Pathway Driven Cancers RAMP 205 • ~180,000 PDAC patients globally with 5 - year relative survival of 13.3% • Avutometinib plus defactinib offer more complete blockade of signaling that drives growth of RAS/MAPK pat
Slide 39: Q&A
Q&A