Slide 1: VS-7375: Potential Best-in-Class KRAS G12D (ON/OFF) Inhibitor R&D Update
VS - 7375 : Potential Best - in - Class KRAS G12D (ON/OFF) Inhibitor R&D Update October 14, 2026
Slide 2: Forward-Looking Statements
2 2 FORWARD - LOOKING STATEMENTS This presentation includes forward - looking statements about, among other things, Verastem Oncology’s (the “Company”) programs an d product candidates, strategy, future plans and prospects, including statements related to the potential safety, efficacy and therapeut
Slide 3: Agenda
3 JULISSA VIANA Senior Vice President, Corp. Comms, IR, Patient Advocacy » Welcome and Agenda DAN PATERSON President and Chief Executive Officer » Delivering on the Strategic Vision for VS - 7375 MICHAEL G. KAUFFMAN, MD, PHD President, Development » Defining the Opportunity for VS - 7375 : Where Cur
Slide 4: Delivering on the Strategic Vision for VS-7375
Delivering on the Strategic Vision for VS - 7375 Dan Paterson President & CEO
Slide 5: Differentiated by Design; Emerging Potential Best-in-Class Profile Across Tumors
5 Differentiated by Design 1,2 • Selective KRAS G12D targeting • Potent, equal ON/OFF inhibition • Dose proportional clinical exposures that are at or above the preclinical target for maximal antitumor efficacy Emerging Potential Best - in - Class Profile Across Tumors • PDAC: Best ORR with CRs • CR
Slide 6: Defining the Opportunity for VS-7375: Where Current & Emerging Therapies Fall Short
Defining the Opportunity for VS - 7375: Where Current & Emerging Therapies Fall Short Michael G. Kauffman, MD, PhD President of Development
Slide 7: Limitations of Current Chemotherapy SoC, panRASi, and Emerging RAS Therapies
7 Limitations of Current Chemotherapy SoC, panRASi, and Emerging RAS Therapies Across Metastatic KRAS G12D - Mutated Cancers No head - to - head studies have been performed. Statements based on publicly available information. SoC: standard of care Other G12D inhibitors appear to have limited to mode
Slide 8: 1L is the Goal: Establishing VS-7375 as Potential Best-in-Class
8 1L is the Goal: Establishing VS - 7375 as Potential Best - in - Class KRAS G12D Inhibitor 1L: first - line; 2L: second - line 1L POTENTIAL A strong standalone profile can support earlier - line use and combination strategies with potential for long - term disease control with good tolerability 2L
Slide 9: Clinical Activity of VS-7375: Pancreatic Ductal Adenocarcinoma
Michael G. Kauffman, MD, PhD President of Development Clinical Activity of VS - 7375: Pancreatic Ductal Adenocarcinoma
Slide 10: VS-7375 900 mg in Previously Treated KRAS G12D mPDAC
10 VS - 7375 900 mg Emerging as Potential Best - in - Class KRAS G12D Inhibitor in Previously Treated (2L - 4L) KRAS G12D mPDAC Data cutoff: Oct. 7, 2026 1: The mITT (modified intent - to - treat) population includes any patient that received at least one dose of VS - 7375 and started therapy on or
Slide 11: First KRAS G12D Inhibitor to Demonstrate Favorable Monotherapy Durability in mPDAC
11 VS - 7375: First KRAS G12D Inhibitor to Demonstrate Favorable Monotherapy Durability in mPDAC 67% Landmark 6 - month PFS rate I 80% Landmark 6 - month OS in 2L/3L/4L Data cutoff: Oct. 7, 2026; The mITT population includes any patient that received at least one dose of VS - 7375 and started therap
Slide 12: VS-7375 Emerging as Potential Best-in-Class RAS Inhibitor in KRAS G12D Pancreatic Cancer
12 VS - 7375 is Emerging as Potential Best - in - Class RAS Inhibitor for Patients with KRAS G12D - Mutated Pancreatic Cancer 50% 35% 41% 30% 1 37% 2 24% 36% 21% 0% 10% 20% 30% 40% 50% 60% ORR 2L 2L+ 3L+ Setidegrasib INCB161734 Zoldonrasib Daraxonrasib VS - 7375 900 mg QD N=14 Setidegrasib INCB16173
Slide 13: 900 mg QD Monotherapy Delivers More Complete KRAS G12D Inhibition
13 VSTM DOF: August 2026; AUCss : area under the curve at steady state; KG: kilogram VS - 7375 900 mg QD Monotherapy Delivers More Complete KRAS G12D Inhibition With a Favorable Therapeutic Window VS - 7375 900 mg QD Monotherapy Achieves the Target Human AUC ss in the Majority of Patients Correspond
Slide 14: 900 mg Achieves High Rates of KRAS G12D VAF Clearance in mPDAC
14 KRAS G12D -100 -50 0 50 100 K R A S G 1 2 D V A F % C h a n g e ( O n - T r e a t m e n t v s . P r e - T r e a t m e n t ) Zoldonrasib (N = 28) KRAS G12D VAF Clearance 24 (86%) > 50% KRAS G12D VAF decrease from pre - treatment, n (%) N.R. > 90% KRAS G12D VAF decrease from pre - treatment, n (%)
Slide 15: 900 mg Achieves Higher Exposure and Deeper Tumor Reductions Than 600 mg
15 Prior LoT Prior LoT Data cutoff: Oct. 7, 2026 1: The mITT population includes any patient that received at least one dose of VS - 7375 and started therapy on or before July 22, 2026 Pts: patients VS - 7375 2L+ PDAC Monotherapy: 900 mg Achieves Higher Exposure and Deeper Tumor Reductions Than 600
Slide 16: Clinical Activity of VS-7375: Colorectal Cancer
Clinical Activity of VS - 7375: Colorectal Cancer Michael G. Kauffman, MD, PhD President of Development
Slide 17: 900 mg Combo with Anti-EGFR Demonstrates Promising Activity in mCRC
17 *ORR included confirmed responses and ongoing unconfirmed responses pending confirmation Data cutoff: Oct. 7, 2026 1: The mITT population includes any patient that received at least one dose of VS - 7375 and started therapy on or before July 22, 2026; 1 pa tient withdrew consent prior to first di
Slide 18: 3L CRC: 900 mg + Anti-EGFR Achieves Deeper Tumor Reductions Than 600 mg
18 Data cutoff: Oct. 7, 2026 1: The mITT population includes any patient that received at least one dose of VS - 7375 and started therapy on or before July 22, 2026 3L CRC: VS - 7375 900 mg + anti - EGFR Combo Achieves Higher Exposure and Deeper Tumor Reductions Than 600 mg in Early Data 600 mg QD +
Slide 19: Clinical Activity of VS-7375: Non-Small Cell Lung Cancer
Clinical Activity of VS - 7375: Non - Small Cell Lung Cancer Michael G. Kauffman, MD, PhD President of Development
Slide 20: Confirmed Responses at 900 mg in 2L+ NSCLC
20 VS - 7375 Demonstrates Confirmed Responses at 600 mg in 2L+ NSCLC 43% c ORR (10/23) 2L+ NSCLC, including prior taxane treated 68 Median age (years) 1 Median prior lines of therapy (range 1 – 3) 17/23 Patients remain on treatment All patients had prior platinum - based chemo Tx, all but 1 patient
Slide 21: Encouraging Durability at 900 mg in 2L+ NSCLC
21 VS - 7375 Shows Encouraging Durability at 600 mg in 2L+ NSCLC 72% landmark PFS rate at 6 - months; mPFS not reached Median Follow - Up: 4.4 months (2.4 — 12.4 months) 17/23 Patients remain on treatment Baseline CR PR SD PD NE Tx ongoing Tx beyond PD Death Circle size represents the extent of bene
Slide 22: Complete KRAS G12D VAF Clearance at 600 mg in Advanced NSCLC
22 1: VSTM DOF Data cutoff: 9/16/2026 Patients with detectable KRAS G12D in ctDNA at baseline and were evaluable for changes in KRA S G12D VAF; 2: Data presented at AACR 2026 meeting with a data cutoff of Dec 1, 2025 PO: by mouth; N: number VS - 7375 Achieved Complete KRAS G12D VAF Clearance Even at
Slide 23: Early Antitumor Activity with First-Line Triplet SoC in NSCLC
23 TPS VS - 7375 at 600 mg Shows Early Antitumor Activity with First - Line Triplet SoC in NSCLC, Supporting Combination Potential Platinum+Pemetrexed ( CPem ) +/ - Pembrolizumab ( Pembro ) in KRAS G12D Adenocarcinoma of the Lung *ORR included confirmed responses and ongoing unconfirmed responses pe
Slide 24: Expert Perspective: The Evolving RAS Treatment Landscape
Manuel Hidalgo Medina, MD, PHD Director of the Gastrointestinal Cancer Center at New York University (NYU) Langone Health and as a professor of medicine at NYU Grossman School of Medicine TARGET - D Investigator Disclosures All statements made and opinions expressed are solely my own and do not refl
Slide 25: Confirmed Partial Response with Monotherapy in 55 y/o Male with mPDAC
25 Confirmed Partial Response at Week 12 with VS - 7375 900 mg Monotherapy in 55 y/o Male with mPDAC • Prior mFOLFIRINOX (SD for 4 mos ) and Gem/NabP (PD after 2 mos ) • Investigator - reported pain resolution within 1 week of treatment (completely off morphine from 100 mg/day) • No treatment - rela
Slide 26: Safety, Tolerability, and Combination Potential
Safety, Tolerability, and Combination Potential Ting - Hui Wu, MD Vice President of Development
Slide 27: 900 mg Monotherapy: High Dose Intensity with Very Low Discontinuations
27 VSTM DOF. Data cut off date: Sep 29, 2026; AE: adverse events; Tx: treatment; TRAEs: treatment - related adverse events; TEAEs: treatment - emergent adverse events. IQR: interquartile range VS - 7375 900 mg Monotherapy: High Dose Intensity with Very Low Discontinuations Due to AEs Across Tumor Ty
Slide 28: Low Rates of Grade ≥3 and Serious TRAEs
28 VS - 7375 900 mg Tolerability is Characterized by Low Rates of Grade ≥3 and Serious TRAEs, Further Supporting it as the Go - Forward Dose 900 mg (N=48) 3.0 (0.2 — 10.6) Median duration of Tx (range), months Gr.3 All Gr. TRAEs 10% 81% Patients with Any TRAE 2% 75% Patients with Any GI TRAE 6% Pati
Slide 29: Predominantly Low-Grade GI Adverse Events Without Accumulation
29 900 mg (N=48) DoT, median (range): 3.0 (0.2 — 10.6) months All Gr., N(%) Gr. ≥4, N(%) Gr. 3, N(%) Gr. 2, N(%) Gr. 1, N(%) Preferred Term GASTROINTESTINAL DISORDERS 28 (58) 0 1 (2) 7 (15) 20 (42) Nausea 23 (48) 0 0 6 (12) 17 (35) Diarrhea 16 (33) 0 0 3 (6) 13 (27) Vomiting VS - 7375: Predominantly
Slide 30: Highly Selective Without AEs Associated with pan-RAS/KRAS Inhibition
30 VS - 7375 900 mg QD is Highly Selective — Without AEs Associated with pan - RAS/KRAS Inhibition 1. Include PT of Rash maculo - papular, Rash, papular, and Rash VSTM: DOF, Data cutoff: September 29, 2026 900 mg (N=48) DoT, median (range): 3.0 (0.2 — 10.6) months All Gr., N(%) Gr. ≥4, N(%) Gr. 3, N
Slide 31: Low Rates of Hematologic Adverse Events at 900 mg
31 VS - 7375: Low Rates of Hematologic Adverse Events at 900 mg VSTM: DOF, Data cutoff: September 29, 2026 900 mg (N=48) DoT, median (range): 3.0 (0.2 — 10.6) months ALL Gr., N(%) Gr. ≥4, N(%) Gr. 3, N(%) Gr. 2, N(%) Gr. 1, N(%) Preferred Term Blood and lymphatic system disorders 3 (6) 0 0 2 (4) 1 (
Slide 32: Low Rates of Liver Related Adverse Events at 900 mg
32 VS - 7375: Low Rates of Liver Related Adverse Events at 900 mg VSTM: DOF, Data cutoff: September 29, 2026 900 mg (N=48) DoT, median (range): 3.0 (0.2 — 10.6) months All Gr., N(%) Gr. ≥4, N(%) Gr. 3, N(%) Gr. 2, N(%) Gr. 1, N(%) Preferred Term Investigations 5 (10) 0 1 (2) 1 (2) 3 (6) Aspartate am
Slide 33: Demonstrates Combinability with SoC Across Indications
33 VS - 7375 Demonstrates Combinability with SoC Across Indications to Address a Broad Population Target Indication(s) VS - 7375 Dose Regimen 900 mg QD 600 mg QD 1L & 2L PDAC 2L+ (mostly 3L+) CRC Cetuximab 1L PDAC GnP 1L NSCLC CPem / Pembro 1L CRC Cetux - mFOLFOX6 DLT cleared DLT evaluation ongoing
Slide 34: Path Forward: PDAC Phase 3 Trial Design & FDA Feedback, Data Summary
Path Forward: PDAC Phase 3 Trial Design & FDA Feedback, Data Summary Michael G. Kauffman, MD, PhD President of Development
Slide 35: NEXT: Advancing to Pursue Parallel Clinical Development Paths
35 1L advanced NSCLC Chemo & IO Combo* 1L mCRC EGFR + Chemo Combo* 1L mPDAC EGFR Combo & GnP Combo NEXT VS - 7375 : Advancing Potential Best - in - Class Profile to Pursue Parallel Clinical Development Paths *Subject to discussions with the FDA. Potential opportunities based on data from ongoing cli
Slide 36: 1L PDAC Phase 3: TARGET-D 301 Study Schema
36 ORR PFS *either panitumumab or cetuximab VS - 7375 1L PDAC Phase 3: TARGET - D 301 Study Schema – Potential for Chemo Free Option 1:1:1 randomization Stratification • ECOG 0 vs 1 • NA vs Europe vs ROW • Liver metastasis + vs - SoC (GnP or FOLFIRINOX) arm crossover to VS - 7375 monoTx (or with a -
Slide 37: Frontline PDAC Phase 3 Protocol – Single Agent Efficacy Matters
37 Frontline PDAC Phase 3 Protocol – Single Agent Efficacy Matters Conceptual schematic only; exact patient - level timing of dose reductions, component discontinuation, and chemotherapy discontinu ation varies by toxicity, response, and protocol. Experimental arms maintain continuous VS - 7375 expo
Slide 38: Establishing VS-7375 as Potential Best-in-Class KRAS G12D Inhibitor
38 Establishing VS - 7375 as Potential Best - in - Class KRAS G12D Inhibitor 1L: first - line; 2L: second - line PROMISING ANTITUMOR ACTIVITY AND A TOLERABLE, COMBINATION - READY PROFILE DRIVES MEANINGFUL AND BROAD OPPORTUNITY 1L POTENTIAL Open 1L mPDAC Phase 3 trial expected by end of 2026; CRC and
Slide 39: Addendum
Addendum W YERASTEM ONCOLOGY
Slide 40: Upcoming Milestones Q4 2026 to 2H 2027
40 • Expect to complete enrollment in the Phase 2 TARGET - D 201 (PDAC) and TARGET - D 203 (CRC) trials by end of 2026. • Expect to report mature data from TARGET - D 101 mCRC 900mg combination cohort and initial data from the mPDAC cetuximab cohort at 600 mg by end of 2026. • Company plans to open
Slide 41: PET Scan Baseline in Patient with mPDAC on 900 mg Monotherapy
41 Baseline Day 17 PET Scan Shows Tumor Metabolic Activity Markedly Reduced After 17 Days on VS - 7375 900 mg Monotherapy in Patient with mPDAC 2L PDAC TARGET - D 201 Phase 2 Study PET: positron emission tomography
Slide 42: PET Scan at Day 21 with 900 mg + Cetuximab Combo
42 SCREENING WEEK 3 By Day 21, PET Scan Shows Tumor Metabolic Activity Markedly Reduced in Patient with mPDAC Treated with VS - 7375 900 mg + Cetuximab Combo 2L PDAC TARGET - D 201 Phase 2 Study
Slide 43: Favorable Monotherapy Durability in mPDAC
43 VS - 7375: First KRAS G12D Inhibitor to Demonstrate Favorable Monotherapy Durability in mPDAC 67% Landmark 6 - month PFS rate I 80% Landmark 6 - month OS in 2L/3L/4L Data cutoff: Oct. 7, 2026; t he mITT population includes any patient that received at least one dose of VS - 7375 and started thera
Slide 44: Encouraging Durability at 900 mg in 2L+ NSCLC
44 VS - 7375 Shows Encouraging Durability at 600 mg in 2L+ NSCLC 72% landmark PFS rate at 6 - months; mPFS not reached Median Follow - Up: 4.4 months (2.4 — 12.4 months) Data cutoff: Oct. 7, 2026; the mITT population includes any patient that received at least one dose of VS - 7375 and started thera
Slide 45: Generally Well Tolerated Without Clear Dose-Dependent Safety Signals
45 VS - 7375 is Generally Well Tolerated Without Clear Dose - Dependent Safety Signals (≥5% of Either 600 mg or 900 mg QD); Consistent with June 2026 as Data Continue to Mature 900 mg (N=48) 600 mg (N=73) System Organ Class Preferred Term mDoT (range) = 3.0 (0.2 - 10.6) mo mDoT (range) = 4.3 (0.5 -
Slide 46: Cetuximab Combo TRAEs: Consistent Tolerability
46 VS - 7375 Cetuximab Combo (TRAE in ≥10% patients) : Consistent Tolerability with the Addition of Cetuximab - associated Rash Subjects are counted only once at their highest grade. Adverse events are graded according to the Common Terminology Criteria fo r Adverse Events v5. MedDRA version V28.0.
Slide 47: GnP Combo TRAEs: Consistent Tolerability
47 VS - 7375 GnP Combo (TRAE reported in ≥2 patients) : Consistent Tolerability with the Addition of Hematological AEs and Neuropathy (most likely associated with GnP ) Subjects are counted only once at their highest grade. Adverse events are graded according to the Common Terminology Criteria fo r
Slide 48: CPPemb Combo TRAEs Outline Combinability
48 VS - 7375 CPPemb Combo (TRAE reported in ≥2 patients) Outlines Combinability VS - 7375 + CCPem Dose Level: 600mg (n=9) System Organ Class Preferred Term All Gr n (%) Gr 4 n (%) Gr 3 n (%) Gr 2 n (%) Gr 1 n (%) Blood and lymphatic system disorders 2 (22) 1 (11) 1 (11) 0 0 Neutropenia 1 2 (22) 0 1
Slide 49: 2L+ mPDAC: Patient Disposition and Baseline Characteristics
49 ECOG: Eastern Cooperative Group Performance Status; LoT : Line of Therapy; SLD: Sum of Longest Diameters (of tumor target lesions selected on baseline scan) Data cutoff Sept. 29. 2026 VS - 7375 : 2L+ mPDAC: Patient Disposition and Baseline Characteristics Baseline Characteristics 66.5 (46 – 79) A
Slide 50: 2L+ mCRC: Patient Disposition and Baseline Characteristics
50 Data cutoff Sept. 29. 2026 VS - 7375 : 2L+ mCRC: Patient Disposition and Baseline Characteristics Baseline Characteristics 55 (35 – 77) Age, years, median (range) Sex, n (%) 5 (83%) Male 1 (17%) Female Race, n (%) 5 (83%) White 1 (17%) Other ECOG, n (%) 4 (67%) 0 2 (33%) 1 3 (50%) Liver mets at e
Slide 51: 2L+ NSCLC: Patient Disposition and Baseline Characteristics
51 Data cutoff Sept. 29. 2026 VS - 7375 : 2L+ NSCLC: Patient Disposition and Baseline Characteristics Baseline Characteristics 68 (30 - 85) Age, years, median (range) Sex, n (%) 14 (61%) Male 9 (39%) Female Race, n (%) 17 (74%) White 4 (17%) Asian 2 (9%) Other ECOG, n (%) 6 (26%) 0 17 (74%) 1 Smokin
Slide 52: Monotherapy: <5% of Patients Discontinue Due to AEs
52 VS - 7375 Monotherapy: <5% of Patients Discontinue Due to AEs Across Tumor Types at the 600 mg and 900 mg Dose Levels 900 mg (N=48) 600 mg (n=73) 3.0 (0.2 — 10.6) 4.3 (0.5 — 11.0) Median follow - up (range), months TRAEs Leading to 2% 3% Discontinuation 6% 10% Reduction 15% 21% Interruption TEAEs
Slide 53: Safety Profile Supports 900 mg as Go-Forward Dose
53 VS - 7375: Safety Profile Supports 900 mg as Go - Forward Dose 900 mg (N=48) 600 mg (n=73) 3.0 (0.2 — 10.6) 4.3 (0.5 — 11.0) Median follow - up (range), months ≥Gr.3 All Gr. ≥Gr.3 All Gr. TRAEs 10% 81% 19% 90% Patients with Any TRAE 2% 75% 11% 86% Patients with Any GI TRAE 6% 5% Patients with Any
Slide 54: 88% of PDAC Patients Had >50% Reduction in CA19-9 or CEA
54 88% of Patients with PDAC treated with 900mg VS - 7375 Monotherapy had a >50% Reduction in CA19 - 9 or CEA Levels from Baseline • 17 PDAC patients treated with 900mg VS - 7375 monotherapy with elevated CA19 - 9 (>38 U/mL) or CEA levels (>5 ng/mL) at baseline and at least one scheduled on - treatm
Slide 55: Complete Response with 900 mg QD Monotherapy in 79 y/o Female with mPDAC
55 Complete Response at Week 12 with VS - 7375 900 mg QD Monotherapy in 79 y/o Female with mPDAC Individual results may not be representative. uPR : unconfirmed partial response; G: Grade.; Tx: therapy Source: TARGET - D 101 investigator • Prior Gem/ NabP (6 mos of Tx) , NALIRI (11 mos of Tx), and F
Slide 56: Maximizing the Opportunity in PDAC Through Monotherapy and EGFR Combination
56 Maximizing the Opportunity in PDAC Through VS - 7375 Monotherapy and EGFR Combination Strategies *All A1 pts with SD allowed to crossover to cetuximab combo if A1 fails to meet efficacy threshold EGFR: Epidermal Growth Factor Receptor R 1:1 randomization Part A: 2L PDAC Cohort A 1 Cohort A2 VS -
Slide 57: Evaluating Monotherapy in Advanced NSCLC, Including Brain Metastases
57 Evaluating VS - 7375 Monotherapy in Advanced NSCLC, Including Patients with Brain Metastases Part A: 2L/3L NSCLC Cohort A VS - 7375 900 mg QD (N=20) Cohort B Preferred dose of VS - 7375 (N=60) Part B: 2L/3L NSCLC Confirm 900 mg QD is the go - forward dose Part C: 2L/3L/4L VS - 7375 900 mg QD with
Slide 58: Combination Strategy with EGFR Inhibitors and Chemotherapy in Metastatic CRC
58 Advancing a VS - 7375 Combination Strategy with EGFR Inhibitors and Chemotherapy in Metastatic CRC #No prior TAS - 102 ( trifluridine and tipiracil ) or regorafenib. VEGFi as appropriate. mFOLFOX : modified oxaliplatin, leucovorin, and 5 - fluorouracil; VEGFI: vascular endothelial Growth Factor R
Slide 59: Significant Unmet Need Remains in Refractory CRC
59 Comparisons based on historical published data; no head - to - head studies have been conducted and cross - trial comparisons may not be reliable due to differences in trial design and patient population and characteristics. mOS , median overall survival; mPFS , median progression - free survival
Slide 60: Verastem Oncology
W VERASTEM ONCOLOGY