Slide 1: VS-7375: Potential Best-in-Class KRAS G12D (ON/OFF) Inhibitor R&D Update Call
VS - 7375 : Potential Best - in - Class KRAS G12D (ON/OFF) Inhibitor R&D Update Call June 23, 2026
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 an d product candidates, strategy, future plans and prospects, including statements related to the approval and commercialization of AVMAPKI®
Slide 3: Agenda and Conference Call Participants
3 3 Agenda and Conference Call Participants JULISSA VIANA SVP, Corporate Communications, Investor Relations and Patient Advocacy Introduction DAN PATERSON President and Chief Executive Officer Opening Remarks MICHAEL KAUFFMAN, MD, PHD President, Development VS - 7375 Clinical Update JON PACHTER, PHD
Slide 4: Opening Remarks
Dan Paterson President & CEO Opening Remarks
Slide 5: Principles that Guided the Design of VS-7375
5 The Principles that Guided the Design of VS - 7375 Potent and equal inhibition of both the ON and OFF states of G12D Enable broad combination strategies Selectively target the KRAS G12D variant Superior oral bioavailability Goal: Drive Maximal Efficacy and Favorable Tolerability for KRAS G12D - Mu
Slide 6: VS-7375 Delivers on These Attributes and More
6 PK: pharmacokinetics VS - 7375 Delivers on These Attributes and More Dose - dependent oral bioavailability to enable maximal target inhibition and efficacy Enables combination strategies Intracranial exposure for the potential to treat brain metastases Stays on the target longer for continuous cov
Slide 7: VS-7375: Well-Positioned to Compete in Pancreatic, Colorectal, and Lung Cancer Markets
7 VS - 7375 : Well - Positioned to Compete in Pancreatic, Colorectal, and Lung Cancer Markets Potential b est - in - class KRAS G12D (ON/OFF) inhibitor Differentiated Profile Efficacy at both 600 mg QD and 900 mg QD in PDAC, NSCLC & CRC Anti - tumor Activity Across Tumors Low - grade GI side effects
Slide 8: Opportunity to Address a Large Patient Population Across KRAS G12D-Mutated Cancers
8 PANCREATIC CANCER 40% Annual U.S. TAM: COLORECTAL CANCER 15% Annual U.S. TAM: LUNG CANCER 5% Annual U.S. TAM: VS - 7375 : Opportunity to Address a Large Patient Population Across KRAS G12D - Mutated Cancers ~29K ~22K ~10K CancerMPact Patient Metrics Active Disease calculation for Stage IV patients
Slide 9: Clinical Update
VS - 7375 Clinical Update Michael Kauffman, MD, PhD President, Development
Slide 10: VS-7375: Competitive Profile Emerging Across Pancreatic, Colorectal and Lung Cancers
10 VS - 7375: Competitive Profile Emerging Across Pancreatic, Colorectal and Lung Cancers AE: adverse event; Gem/NabP: gemcitabine, nab - paclitaxel; 1L: first - line; 1H: first - half Safety Profile Significantly Improved After Cycle 1 Combinability with SOC Therapies Multiple Paths to Registration
Slide 11: Enrolled 150+ Patients Across Dose Escalation & Expansion Cohorts
11 Enrolled 150+ Patients Across Dose Escalation & Expansion Cohorts Phase 1/2 Study Evaluating VS - 7375, a KRAS G12D (ON/OFF) inhibitor, as Monotherapy and in Combination, in Patients with KRAS G12D - Mutated Solid Tumors The study is dosing with meals and using prophylactic antiemetics NCT0702022
Slide 12: VS-7375 Achieves Targeted Human AUCss in Majority of Patients
12 900 mg QD of VS - 7375 Achieves the Targeted Human AUC ss in the Majority of Patients Corresponding to Maximal Tumor Regression Across Mouse Models 400mg QD 600mg QD 900mg QD Equivalent exposure to mice at 100 mg/kg (PR in almost all mice in 4 tumor models) Equivalent exposure to mice at 10 mg/kg
Slide 13: mPDAC: VS-7375 Demonstrates Promising Preliminary Efficacy
13 mPDAC: VS - 7375 900 mg Demonstrates Promising Preliminary Efficacy; Deeper and More Rapid Responses Seen with Cetuximab Combination KEY OBSERVATIONS: METASTATIC PANCREATIC DUCTAL CARCINOMA 2 - 4L mPDAC Towards 1L mPDAC As of June 2026: 7 of 20+ patients at the 600 mg dose with ≥6 months of follo
Slide 14: 93% of mPDAC Patients at 900 mg QD Achieved >50% Reduction in CA19-9
14 14 patients dosed at 900 mg QD had elevated levels of CA19 - 9 at baseline (>37 U/mL) and at least one scheduled on - treatment measurement – All patients remain on treatment – Includes 2 - 4L patients 93% (13/14) of patients showed >50% reduction in CA19 - 9 ≥50% reduction in CA19 - 9 has been c
Slide 15: Confirmed Partial Response with Monotherapy in 55 y/o Male with mPDAC
15 Confirmed Partial Response at Week 12 with VS - 7375 900 mg QD 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 - r
Slide 16: Complete Resolution of Target Lesion in 79 y/o Female with mPDAC
16 Complete Resolution of Target Lesion at Week 6 with VS - 7375 900 mg QD Monotherapy in 79 y/o Female with mPDAC 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 FOLFOX (3 mos of Tx) • Investi
Slide 17: Deep and Rapid Response at 400 mg QD + Anti-EGFR in mPDAC
17 Source: VS - 7375 TARGET - D 101 investigator; RT: radiotherapy; TEAE: treatment - emergent adverse event Baseline Lesion: Pleura, lung, mediastinum lymph node (52mm) 7x5mm 9x7mm Week 6: cPR ( - 46%) (28mm) Week 12: cPR : ( - 70%) (16mm) Deep and Rapid Response Achieved at Subtherapeutic Dose wit
Slide 18: mCRC: Preliminary Efficacy Observed with Cetuximab Combination
18 As of June 2026 mCRC: Preliminary Efficacy Observed with Cetuximab Combination at Both VS - 7375 600 mg QD & 900 mg QD KEY OBSERVATIONS: METASTATIC COLORECTAL CANCER As of June 2026: All patients (20+) at the 600 mg dose in combination with cetuximab have ≤6 months of follow - up 900 mg + full do
Slide 19: Marked Reduction of Disease Burden with VS-7375 + Cetuximab in mCRC
19 Marked Reduction of Disease Burden with VS - 7375 600 mg QD + Cetuximab in Heavily Pre - treated 42 y/o Male with mCRC Source: TARGET - D 101 Investigator Week 12: SD: ( - 29.5%) (SLD: 260mm) Baseline Lesion: (SLD: 370mm) 0 500 1000 1500 2000 2500 3000 3500 4000 4500 0 3 6 9 12 CEA (ng/mL) Time o
Slide 20: Advanced NSCLC: Preliminary Efficacy Observed at 600 mg QD
20 As of June 2026 Advanced NSCLC: Preliminary Efficacy Observed at VS - 7375 600 mg QD; Ongoing Evaluation at 900 mg QD KEY OBSERVATIONS: ADVANCED NON - SMALL CELL LUNG CANCER As of June 2026: 1 of 20+ patients at the 600 mg dose (single agent) has ≥6 months of follow up Expect to complete enrollme
Slide 21: Confirmed Partial Response at 600 mg QD in Advanced NSCLC
21 Week 12: cPR ( - 49%) (SLD: 35mm) Baseline Lesion: (SLD 69mm) Source: TARGT - D 101 investigator Confirmed Partial Response at Week 6 with Deepening of Response Through Week 12 at VS - 7375 600 mg QD in 77 y/o Female with Advanced NSCLC ▪ Prior therapy of Pemetrexed - Carbo - Pembro (SD 4 mos ) ▪
Slide 22: Safety Update
VS - 7375 Safety Update Michael Kauffman, MD, PhD President, Development
Slide 23: Safety Summary: Favorable Tolerability Profile Across Monotherapy and Combinations
23 VS - 7375 Safety Summary: Favorable Tolerability Profile Across Monotherapy and Combinations Primarily low - grade nausea, vomiting, diarrhea Nearly all respond to standard prophylactic treatment No unexpected AEs and low rates of Grade 3 AEs No clinically - meaningful cytopenias or liver functio
Slide 24: Well-Tolerated Up To 900 mg; Low-Grade GI AEs
24 TRAEs: treatment - related adverse events; Neutropenia' and 'Neutrophil count decreased' are grouped as 'Neutropenia’ VSTM: DOF, Data cutoff: June 12, 2026 VS - 7375 Well - Tolerated Up To 900 mg; Low - Grade GI AEs Most Common TRAEs reported in >1 patient 900 mg (N=25) 600 mg (N=57) All Gr. n(%)
Slide 25: Major TRAEs Largely Attenuated After Cycle 1
25 VSTM: DOF, Data cutoff: June 12, 2026 Major TRAEs Largely Attenuated After Cycle 1 on Both VS - 7375 600 mg QD & 900 mg QD 900 mg (N=22) 600 mg (N=51) All Gr. n(%) Gr. ≥4 n(%) Gr. 3 n(%) Gr. 2 n(%) Gr. 1 n(%) All Gr. n(%) Gr. ≥4 n(%) Gr. 3 n(%) Gr. 2 n(%) Gr. 1 n(%) System Organ Class / Preferred
Slide 26: Positioning for Broad Registrational Development Across Multiple Indications
26 Positioning VS - 7375 for Broad Registrational Development Across Multiple Indications Complete enrollment in all three Phase 2 trials by the end of 2026 Enroll the first patient in each of the Phase 3 pivotal trials by 1H 2027 TARGET - D 201 ( NCT07644559 ) , TARGET - D 202 ( NCT07659782 ) . TAR
Slide 27: Rationale for New Clinical Collaborations
Rationale for New Clinical Collaborations with VS - 7375 Jonathan Pachter, PhD Chief Scientific Officer
Slide 28: Potential Best-in-Class G12D Inhibitor for Advanced KRAS G12D-Mutated Cancers
28 Pachter et al., Targeting RAS 2nd edition 2025; Ai et al., ASCO 2025; Li et al., World Conference of Lung Cancer 2025; pERK: pho sphorylated Extracellular signal - regulated Kinase; GEF: Guanine nucleotide exchange factor GAP: GTPase - activating protein VS - 7375: Potential Best - in - Class G12
Slide 29: VS-7375 + Pan-RAS Tricomplex Inhibitor Yields More Sustained Tumor Regression
29 Combination of VS - 7375 with a Pan - RAS Tricomplex Inhibitor Yields More Sustained Tumor Regression than Combination of Zoldonrasib + Daraxonrasib KP4 KRAS G12D PANCREATIC CANCER MODEL 0 20 40 60 0 500 1000 1500 2000 2500 Days after first dose T u m o r v o l u m e ( m m 3 ± S E M ) Vehicle VS-
Slide 30: VS-7375 + PRMT5 Inhibitor Induces Sustained Tumor Regressions
30 Combination of VS - 7375 + PRMT5 Inhibitor Induces Dramatic Sustained Tumor Regressions in KRAS G12D/MTAP - Del PDAC Models PACX020 PANCREATIC CANCER MODEL All mice (8/8) showed complete responses with VS - 7375 + navlimetostat (PRMT5 inhibitor) 0 20 40 60 80 0 250 500 750 1000 1250 1500 Days aft
Slide 31: Closing Remarks
Closing Remarks Dan Paterson, President & CEO
Slide 32: VS-7375: Aiming to Define Treatment for KRAS G12D-Mutated Cancers
32 VS - 7375 : Aiming to Define Treatment for KRAS G12D - Mutated Cancers Coma et al., AACR 2026 Selective KRAS G12D Inhibition Across Tumor Types Compelling Emerging Clinical Profile Potential Franchise Opportunity Pancreatic Cancer Colorectal Cancer Lung Cancer Other G12D Cancers SœJAJy a^IV_AIV]V
Slide 33: Thank you!
Thank you! VW YERASTEM ONCOLOGY
Slide 34: Q&A
Q&A VW YERASTEM ONCOLOGY
Slide 35: Appendix
Appendix VW YERASTEM ONCOLOGY
Slide 36: Well-Tolerated Up to 900 mg QD Monotherapy: TEAEs in ≥5% of Patients
36 Neutropenia' and 'Neutrophil count decreased' are grouped as 'Neutropenia’. VSTM: DOF, June 12. 2026 data cutoff VS - 7375 Well - Tolerated Up to 900 mg QD Monotherapy Treatment - Emergent Adverse Events (TEAEs) reported in ≥5% of patients 900 mg (N=25) 600 mg (N=57) SOC / Preferred Term All Gr.
Slide 37: Key Milestones
37 VS - 7375 Key Milestones x First patient dosed in TARGET - D 201 Registration - Directed Trial June 2026 • Complete enrollment across all three TARGET - D Phase 2 Trials • Report an update on TARGET - D 101 across tumor types and more follow up Mid - 2026 2H 2026 End of 2026 1H 2027 • Enroll firs