Summary of Immunome FY Conference Call (November 11, 2025) Company Overview - **Company**: Immunome (NasdaqCM:IMNM) - **Focus**: Standalone pure-play cancer company specializing in targeted therapies, including antibody-based therapies, radioligands, and small molecules [1][1] Key Points on Varegacestat - **Asset**: Varegacestat, a gamma-secretase inhibitor, is nearing completion of phase three clinical trials for desmoid tumors [2][2] - **Market Opportunity**: The commercial opportunity in desmoid tumors is substantial, with approximately 1,650 new cases per year in the US and a prevalence of about 30,000 [9][15] - **Differentiation**: Varegacestat is expected to differentiate itself from Ogsivo (nirogacestat) due to better efficacy and dosing convenience (once daily vs. twice daily) [10][10][22][22] - **Phase 2 Data**: Phase 2 data indicated a significant improvement over nirogacestat, with a median tumor volume reduction that was 20-25% better [10][10] - **Regulatory Readiness**: The company is well-prepared for regulatory submission and product launch, with a strong team in place [14][14] Clinical Trial Insights - **Enrollment**: Enrollment for the phase 3 trial was completed in February 2024, with data expected to be released soon [11][11] - **Data Monitoring**: A Data Safety Monitoring Board (DSMB) has been overseeing the trial, ensuring safety and compliance [24][24] - **Comparison with Competitors**: The trial design and patient enrollment criteria are nearly identical to those used in SpringWorks' trial for nirogacestat, which is considered the gold standard [17][18] ADC Development - **ROR1 ADC**: Immunome is developing an antibody-drug conjugate (ADC) targeting ROR1, utilizing a proprietary payload (HC74) [27][27] - **Technology Differentiation**: The ADC aims to improve upon existing technologies by addressing common resistance pathways and enhancing permeability for better therapeutic activity [32][32][33][33] - **Future Pipeline**: The company plans to introduce additional ADCs in 2026 and 2027, with a focus on high internalization antibodies [34][34] Market Potential - **Revenue Potential**: A drug targeting 3,000 patients could generate over a billion dollars in revenue, with a significant number of treatable patients available in the US and Europe [15][15] - **Patient Compliance**: The once-daily dosing of Varegacestat is expected to improve patient compliance compared to competitors [10][10] Conclusion - Immunome is positioned to capitalize on the growing market for targeted cancer therapies, with a strong focus on developing innovative treatments that offer significant advantages over existing options. The upcoming data release for Varegacestat is highly anticipated and could be a pivotal moment for the company.

Key Highlights of SpringWorks Therapeutics - OGSIVEO (nirogacestat) is the first and only FDA-approved therapy for desmoid tumors[15] - GOMEKLI (mirdametinib) is the first and only FDA-approved therapy for both adults and children with NF1-PN[15] - SpringWorks Therapeutics expects profitability in the first half of 2026[10] - SpringWorks Therapeutics had $461.9 million in cash, cash equivalents, and marketable securities[132] OGSIVEO (Nirogacestat) for Desmoid Tumors - OGSIVEO generated $61.5 million in net revenue in Q4 2024 and $172.0 million in FY 2024[15] - Between October 2023 and October 2024, approximately 11,000 patients with desmoid tumor ICD-10 claims were identified[15] - Objective response rate (ORR) increased from 34.3% with up to 1 year of treatment to 45.7% with up to 4 years of treatment[48] GOMEKLI (Mirdametinib) for NF1-PN - GOMEKLI is approved for the treatment of adult and pediatric patients 2 years of age and older with NF1-PN[10] - The U S market includes approximately 30,000 adult and 10,000 pediatric patients with NF1-PN[15] - In clinical trials, GOMEKLI showed a confirmed overall response rate of 41% in adults (n=58) and 52% in pediatrics (n=56)[67]

Core Insights - Nirogacestat is poised to become the first and only approved therapy in the EU for desmoid tumors if the European Commission grants marketing authorization, with a decision expected in Q3 2025 [1][2] Company Overview - SpringWorks Therapeutics, Inc. is a biopharmaceutical company focused on severe rare diseases and cancer, currently advancing nirogacestat for desmoid tumors [2][10] - The company has previously received Orphan Drug designation for nirogacestat from the European Commission [3] Clinical Trial Results - The positive opinion from the EMA's CHMP is based on the Phase 3 DeFi trial, which demonstrated a 71% lower risk of disease progression for nirogacestat compared to placebo [3][6] - The DeFi trial involved 142 patients, with nirogacestat showing significant improvements in progression-free survival, objective response rate, and patient-reported outcomes [6] Safety Profile - Nirogacestat has a manageable safety and tolerability profile, with common adverse reactions including diarrhea, nausea, and fatigue [4] Disease Context - Desmoid tumors are rare, aggressive tumors with an estimated 1,300-2,300 new cases diagnosed annually in the EU, predominantly affecting individuals aged 20 to 44 [7][8] - Despite not metastasizing, desmoid tumors have high recurrence rates, leading to a shift in treatment guidelines recommending systemic therapies as first-line interventions [8]

Core Viewpoint - SpringWorks Therapeutics, Inc. anticipates a favorable opinion from the CHMP of the EMA regarding the marketing authorization application for nirogacestat in Q2 2025, aimed at treating adults with desmoid tumors [1] Company Overview - SpringWorks Therapeutics is a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, with FDA-approved products including OGSIVEO (nirogacestat) for desmoid tumors and GOMEKLI™ (mirdametinib) for neurofibromatosis type 1 associated plexiform neurofibromas [2]