Slide 1: Immunome Corporate Presentation
Immunome Corporate Presentation September 2026 1
Slide 2: Disclaimer and Forward-Looking Statements
Disclaimer and Forward-Looking Statements Disclosures For purposes of this notice, the “presentation” that follows shall mean and include the slides that follow, any oral presentation of the slides by members of management of Immunome, Inc. (“Immunome”) or any person s behalf, any question-and- answ
Slide 3: Establishing a Premier Targeted Oncology Company
Establishing a Premier Targeted Oncology Company Delivering Breakthroughs In Oncology i • Varegacestat, an oral, once-daily gamma secretase inhibitor for the treatment of desmoid tumors that is positioned to be a best-in-class option • Positive topline data reported in December 2025, with detailed d
Slide 4: Broad Portfolio of Targeted Oncology Therapeutics
Broad Portfolio of Targeted Oncology Therapeutics Program Target / Modality Preclinical Phase 1 Phase 2 Phase 3 Commercial Key Milestone Varegacestat Gamma Secretase PDUFA Date | April 28, 2027 Inhibitor IM-1021 ROR1 ADC Initial Lymphoma Data | Expected 2026 IM-1617 First-in-Class Solid First Patien
Slide 5: Varegacestat
Varegacestat Phase 3 Oral, Once-Daily Gamma Secretase Inhibitor 5
Slide 6: Varegacestat Demonstrated Exceptional Results For Patients
Varegacestat Demonstrated Exceptional Results For Patients Study Met Primary and All Key Secondary Endpoints Progression-Free Survival1: Hazard Ratio 0.16 (p<0.0001) Confirmed Objective Response Rate 2: 56% Median Best Tumor Volume Reduction 3: 83% Generally well-tolerated with manageable safety pro
Slide 7: Desmoid Tumors are Locally Aggressive & Debilitating
Desmoid Tumors are Locally Aggressive & Debilitating • Desmoid tumors often strike in young adulthood, with 1,000-1,650 patients diagnosed each year and 10-11,000 actively managed patients in the US1 • Can lead to debilitating pain, deformity, and life-threatening organ damage depending on location1
Slide 8: Varegacestat is a Gamma Secretase Inhibitor with a Differentiated Pharmacokinetic Profile
Varegacestat is a Gamma Secretase Inhibitor with a Differentiated Pharmacokinetic Profile 78% Longer Half-Life than Nirogacestat3 Sustained Exposure Above Target Threshold4,5 Kasper et al. 1.2 mg Once Daily Desmoid tumors are driven by nuclear accumulation of β- CATENIN resulting from cross-talk bet
Slide 9: RINGSIDE is the Largest Phase 3 Study in Desmoid Tumors
RINGSIDE is the Largest Phase 3 Study in Desmoid Tumors Design consistent with prior registrational trials Global Phase 3 Double-Blind Placebo-Controlled Key Inclusion Criteria Progressed within last 12 months 1 Varegacestat 1.2mg QD, n=79 Treatment naïve or recurrent/refractory R disease appropriat
Slide 10: Varegacestat Achieved Primary Endpoint
Varegacestat Achieved Primary Endpoint 84% Reduction in the Risk of Progression or Death vs Placebo Progression-Free Survival: HR 0.16; 95% CI: 0.071, 0.375; p < 0.0001 10
Slide 11: Varegacestat Demonstrates Robust Antitumor Activity
Varegacestat Demonstrates Robust Antitumor Activity 56% ORR With Varegacestat -83% Median Best Percent Change in Tumor vs 9% With Placebo (p<0.0001) Volume With Varegacestat vs +11% With Placebo Best Percent Change in Tumor Size with Varegacestat PD PR Par -83% 11
Slide 12: Varegacestat Achieved Key Secondary Endpoint of Reduction in Worst Pain Intensity
Varegacestat Achieved Key Secondary Endpoint of Reduction in Worst Pain Intensity Change In Worst Pain Intensity Score Statistically significant reduction in Change in Worst Pain Intensity Score worst pain intensity1 at week 12: • Varegacestat: −2.24 (0.27) Placebo Worsening • Placebo: +0.18 (0.27)
Slide 13: Varegacestat Was Generally Well-Tolerated, With a Manageable Safety Profile
Varegacestat Was Generally Well-Tolerated, With a Manageable Safety Profile Consistent With the GSI Class Varegacestat Placebo (n=79) (n=77) Adverse Events, n (%) Any grade Grade 3+ Any grade Grade 3+ • Most events (95%) were Any adverse event 79 (100) 45 (57) 70 (91) 13 (17) grade 1 or 2 Reported i
Slide 14: Elevating an Established Class and Solidifying the Role of GSIs
Elevating an Established Class and Solidifying the Role of GSIs in Desmoid Tumor Treatment Phase 3 Studies in Desmoid Tumors TKI Era GSI Era Varegacestat 1.2mg Once-Daily Oral Nirogacestat RINGSIDE; N=156 150 mg Twice-Daily Oral ORR: 56% Sorafenib DeFi; n=142 400mg Once Daily Oral NCT02066181; N=87
Slide 15: Launch Strategy
Launch Strategy Become Standard of Care treatment of Desmoid Tumors START SUPPORT SCALE Drive patient initiation on Sustained benefit and adherence Efficiently expand reach across varegacestat with a once-daily treatment the community through treatment center growth 10-11k Actively Managed Patients
Slide 16: IM-1021 ROR1 ADC
IM 1021 ROR1 ADC 16
Slide 17: IM-1021: Potential Best-in-Class ROR1 ADC
IM-1021: Potential Best-in-Class ROR1 ADC ROR1 ROR1 ROR1 Expression Expression by by RNA 2 RNA2 • Receptor with oncofetal expression pattern, including little or no normal tissue expression1 • Expression on solid and liquid tumors IM-1021 Development Status • Optimized ROR1 ADC with HC74 TOP1i paylo
Slide 18: Large Patient Populations Across Key Non-Hodgkin Lymphoma Subtypes
Large Patient Populations Across Key Non-Hodgkin Lymphoma Subtypes 5-Year Relative Drug-Treated Patients Survival1,2 (U.S., 1L, 2026)3 Aggressive Disease Diffuse Large B-Cell ~65% ~28K Mantle Cell ~66% ~4K Indolent Follicular Lymphoma ~89% ~11K Disease 1. SEER (2016-2022): “relative survival is an e
Slide 19: IM-1021 Preclinical Activity Supports Development in Lymphoma and Solid Tumors
IM-1021 Preclinical Activity Supports Development in Lymphoma and Solid Tumors IM-1021 Achieves Tumor Regressions in IM-1021 Achieves 8/8 CRs at 2.5 mg/kg in Jeko-1 MCL Model NSCLC PDX Model Vehicle 2,500 IM-1021 2.5 mpk qw*3 2500 IM-1021 5 mpk qw*3 Vehicle IM-1021 2.5 mpk qw*3 MK-2140 2.5 mpk qw*3
Slide 20: Clinical Development Plan: Rapid Establishment of PoC to Enable Pivotal Studies
Clinical Development Plan: Rapid Establishment of PoC to Enable Pivotal Studies Across Multiple Indications Part A: Dose Escalation Part B: Indication-Specific Dose Expansion Population includes: Dose escalation design: Population includes: Dose expansion design: • R/R B-cell lymphoma • mTPI-2 adapt
Slide 21: HC74 Platform
HC74 Platform 21
Slide 22: HC74 is a TOP1i Payload Designed to Overcome Fundamental Limitations of Existing Technology
HC74 is a TOP1i Payload Designed to Overcome Fundamental Limitations of Existing Technology 26 Years of ADC Technological Advancement VcMMAE TOP1i HC74 First Approved ADC Linker-Payload Payloads ADCs 2000 2011 2019 2026+ X Unstable linker Stable peptide linker Improved therapeutic index Improv
Slide 23: HC74's Low Efflux Potential and High Permeability Lead to Improved Properties
HC74’s Low Efflux Potential and High Permeability Lead to Improved Properties Low Low HC74 HC74 efflux efflux potential potential11 drives High HC74 permeability22 drives Superior HC74 Superior HC74 cytotoxic cytotoxic overcomes overcomes payload payload resistance resistance superior bystander eff
Slide 24: Sensitivity to Efflux Meaningfully Limits the Clinical Efficacy of Existing TOP1i ADCs
Sensitivity to Efflux Meaningfully Limits the Clinical Efficacy of Existing TOP1i ADCs Efflux Transporters Like P-gp and MRP1 Actively High HighP-gp P-gpExpression ExpressionCorrelates CorrelatesWith WithLower LowerORR ORRand andPFS PFSininHER2+ HER2+CRC CRCPatients PatientsTreated TreatedWith WithT
Slide 25: HC74 ADC Shows Activity in a CRC Model Refractory to Other TOP1i Agents
HC74 ADC Shows Activity in a CRC Model Refractory to Other TOP1i Agents HCT-15 is Refractory to T-DXd HCT-15 is Refractory to Irinotecan HCT-15 is Refractory to T-DXd but HCT-15 is Refractory to Irinotecan but But Sensitive to T-HC74 But Sensitive to T-HC74 Sensitive to T-HC74 Sensitive to T-HC74 20
Slide 26: HC74 ADC Demonstrates Superior Bystander Activity vs. DXd ADC
HC74 ADC Demonstrates Superior Bystander Activity vs. DXd ADC Potential for Greater HC74 Efficacy in Target Heterogenous Tumors Clonal Preclinical Models Do Not Capture HC74 ADC Demonstrates Durable Response in Expression Heterogeneity NSCLC Model of Tumor Heterogeneity NCI-H292 Bystander Model 2000
Slide 27: Expanding the Universe of ADC Targets
Expanding the Universe of ADC Targets Majority of ADC Activity is Concentrated in a Small Immunome ADC Strategy Pairs Novel Number of Targets Targets with Differentiated Technology 10 Targets Account for 50% of Active Clinical ADC Programs 1 • Targets: Prioritize targets with compelling tumor biolog
Slide 28: IM-1617: Potential First-in-Class ADC for Multiple Solid Tumor Indications
IM-1617: Potential First-in-Class ADC for Multiple Solid Tumor Indications Target Expression In Major Indications Corresponds IM-1617 Showed Activity In PDX Models That Are to CDX Models Where IM-1617 Showed Activity Resistant to Dato-DXd Adeno NSCLC IM-1617 Target mRNA Expression 10 Squamous NSCLC
Slide 29: Robust Pipeline of Preclinical Candidates Pursuing Undisclosed Solid Tumor Targets
Robust Pipeline of Preclinical Candidates Pursuing Undisclosed Solid Tumor Targets IM-1617 ✓ IM-1340 IM-1335 TNBC Adeno NSCLC Solid tumor model (MDA-MB-468) (LU5205 PDX) 2000 600 Vehicle 1500 IM-1340, 5mg/kg Tumor Volume (mm3) Isotype ADC, 5 mg/kg Tumor Volume (mm3) Anticipated Tumor Volume (mm3) IM
Slide 30: IM-3050 FAP-Targeted Radioligand Therapy
IM-3050 FAP-Targeted Radioligand Therapy 30
Slide 31: IM-3050 is a 177Lu-FAP Candidate with Best-in-Class Potential
IM-3050 is a 177Lu-FAP Candidate with Best-in-Class Potential In vivo data show single dose antitumor activity and tolerability Tumor Regression in U87MG Model No Weight Loss Observed Potential Best-in-Class Characteristics Vehicle Vehicle Sub-nanomolar affinity 1200 120 IM-3050, 150 mCi IM-3050, 15
Slide 32: Company Overview
Company Overview a _ see
Slide 33: Management Team with a Demonstrated Track Record of Success
Management Team with a Demonstrated Track Record of Success Clay Siegall, Ph.D. • Chief Executive Officer and Founder, Seagen (1998-2022) PRESIDENT & • Grew company to $2B+ revenue (2022) leading to $43B acquisition CHIEF EXECUTIVE OFFICER • Led development of 4 FDA-approved therapeutics • Raised ov