Slide 1: Topline Results of the RINGSIDE Phase 3 Study of Varegacestat in Desmoid Tumors
Topline Results of the RINGSIDE Phase 3 Study of Varegacestat in Desmoid Tumors Investor Webcast Dec 15, 2025 1
Slide 2: Forward Looking Statements
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 on its behalf, any question-and- answer session
Slide 3: Agenda
Opening Remarks Clay Siegall, PhD RINGSIDE Topline Results Bob Lechleider, MD AGENDA Treatment Landscape Mrinal Gounder, MD Memorial Sloan Kettering Cancer Center Commercialization Roee Shahar Next Steps & Close Clay Siegall, PhD
Slide 4: Clay Siegall, PhD, President and CEO
Clay Siegall, PhD President and CEO
Slide 5: 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 Rate2: 56% Median Best Tumor Volume Reduction3: 83% Generally well-tolerated with manageable safety profi
Slide 6: Bob Lechleider, MD, Chief Medical Officer
Bob Lechleider, MD Chief Medical Officer
Slide 7: 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 betw
Slide 8: 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 months1 Varegacestat 1.2mg QD, n=79 • Treatment naïve or recurrent/refractory R disease appropr
Slide 9: 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
Slide 10: 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% 10
Slide 11: Varegacestat was Generally Well-tolerated with a Manageable Safety Profile
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 of medicines • The most common adverse events for participants in the treatment arm were diarrhea (82%), fatigue (44%
Slide 12: Next Steps
Next Steps • Thank you to the patients and investigators in the RINGSIDE study • New Drug Application expected for varegacestat during 2Q 2026 • Presentation of full data from RINGSIDE Phase 3 anticipated at an upcoming medical conference • Additional clinical trials planned
Slide 13: Mrinal Gounder, MD
Mrinal Gounder, MD Sarcoma Medical Oncologist Drug Development Specialist Memorial Sloan Kettering Cancer Center
Slide 14: 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 in the US1 • Can lead to debilitating pain, deformity, and life-threatening organ damage depending on location1 • Quality of life is a major challenge
Slide 15: Unmet Need Remains for Effective, FDA-approved Therapies Suitable for Chronic Nature of Desmoid Tumors
Unmet Need Remains for Effective, FDA-approved Therapies Suitable for Chronic Nature of Desmoid Tumors Treatment & Management of Desmoid Tumors Why We Need More Treatment Options Spontaneous regression is not common 1,2,3,6,7 Active Surveillance Tumor location limits feasibility; Up to 77% recurrenc
Slide 16: Elevating an Established Class and Solidifying the Role of GSIs in Desmoid Tumor Treatment
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 17: Patient Case: A Decade of Disease, a Dramatic Reduction in Tumor Volume Within Months
Patient Case: A Decade of Disease, a Dramatic Reduction in Tumor Volume Within Months Treated in Patient History Surgery Sorafenib RINGSIDE (part A) 1.2mg (‘21-24) • Diagnosed in 2010 Imatinib • A 25 Y/O male patient, with a pelvic and left leg Hydroxy Urea desmoid tumor • No history of FAP (Familia
Slide 18: Data Support Potential For Varegacestat to Become SOC in the Treatment of Desmoid Tumors
Data Support Potential For Varegacestat to Become SOC in the Treatment of Desmoid Tumors RINGSIDE is the largest randomized Phase 3 trial in desmoid tumors • PFS, ORR, Tumor Volume reduction are best in class Progression-free survival hazard ratio of 0.16 is striking Safety profile is manageable and
Slide 19: Roee Shahar, EVP - Commercial
Roee Shahar EVP - Commercial
Slide 20: 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 21: Differentiated Clinical Profile and Commercial Execution Expected to Support Rapid Adoption
Differentiated Clinical Profile and Commercial Execution Expected to Support Rapid Adoption Commercial Team Market Access Market Shaping Readiness • Distribution & supply • Commercial hires • US & EMA orphan • KOL familiarity chain leverages prior have demonstrated designation has expected to oncolo
Slide 22: Patient Support is Key for the Success of Varegacestat
Patient Support is Key for the Success of Varegacestat “The promising results with varegacestat from the RINGSIDE trial drive forward the shared mission of finding effective, safe therapies and ultimately a cure for every person living with a desmoid tumor." Lynne Hernandez & Katie Doyle Myers – Exe
Slide 23: Clay Siegall, PhD, President and CEO
Clay Siegall, PhD President and CEO
Slide 24: Accelerating the Pursuit of Breakthrough Oncology Therapies
Accelerating the Pursuit of Breakthrough Oncology Therapies Proven, successful leadership Multiple programs ADC portfolio including the Varegacestat at approval expected to enter clinic in HC74 platform represents provides strong first 2026 substantial value product Anticipated Milestones Varegacest