Slides
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Immunome Corporate Presentation November 2025
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2 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 that follows that oral presentation, hard copies of this document and any materials distributed at, or in connection with, that presentation. References to “we,” “our,” and “us” refers to Immunome and its subsidiaries. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy any Immunome securities. Forward-Looking Statements Statements in this presentation that are not purely historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. We use words such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “vision,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “promising,” “projected,” “first step,” “ongoing,” or the negative of these terms, and similar words or expressions to identify these forward-looking statements. These forward-looking statements include, but are not limited to, statements about: the expansion and advancement of our platform and pipeline and our approach; the expected benefits of our proprietary payload, HC74; and strategy related to our platform and pipeline; assessments of the clinical efficacy, best-in-class potential, and potential commercial success of our product candidates, including IM-1021 and varegacestat; the potential of our current and future pipeline to produce first-in-class and/or best-in-class drugs; our expectations with respect to future performance, anticipated financial impacts, ability to complete and success of our strategic transactions; our timeline for filing INDs and other regulatory filings, commencing clinical trials, receiving and reporting data from such clinical trials, and seeking regulatory approval, for our current and future programs and product candidates and other anticipated milestones; our expected cash runway; our ability to expand our platform, establish a broad pipeline and advance it through efficient clinical development decisions; our intention to continue expanding our pipeline through internal efforts and/or strategic transactions; our intention to expand our intellectual property portfolio; and other statements regarding management’s intentions, plans, beliefs, expectations or forecasts for the future. These forward-looking statements are based on Immunome’s current expectations and involve assumptions that may never materialize or may prove to be incorrect; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including, but not limited to, the risk that Immunome will not be able to realize the benefits of its strategic transactions; the risk that regulatory approvals for Immunome’s programs and product candidates are not obtained, are delayed or are subject to unanticipated conditions; the risk that preclinical or early clinical data may not be predictive of future results; the risk that Immunome’s product candidates and development candidates fail to achieve their intended endpoints; the reliance on Immunome’s management; the prior experience and successes of Immunome’s management team not being indicative of any future success; the risk of reliance on vendors; uncertainties related to Immunome’s capital requirements and Immunome’s expected cash runway; Immunome’s ability to grow and successfully execute on Immunome’s business plan, including the development and commercialization of its pipeline and integration of newly acquired assets; and other risks and uncertainties indicated from time to time described in Immunome’s Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on March 19, 2025, and in Immunome’s other filings with the SEC. Except as required by law, Immunome assumes no obligation and does not intend to update any forward-looking statements included in this presentation. Product Candidates In this presentation, we may discuss current and potential future product candidates that have not yet undergone clinical trials or been approved for marketing by the U.S. Food and Drug Administration or other governmental authority. No representation is made as to the safety or effectiveness of these current or potential future product candidates for the use for which such product candidates are being studied. Industry and Market Data In this presentation, we rely on and refer to publicly available information and statistics regarding market participants in the sectors in which we compete and other industry data. Any comparison of us to the industry or to any of our competitors is based on this publicly available information and statistics and such comparisons assume the reliability of the information available to us. We obtained this information and statistics from third-party sources, including reports by market research firms and company filings. While we believe such third-party information is reliable, there can be no assurance as to the accuracy or completeness of the indicated information. We have not independently verified the information provided by the third-party sources. Trademarks This presentation may contain trademarks, service marks, trade names and copyrights of other companies, which are the property of their respective owners. Solely for convenience, some of the trademarks, service marks, trade names and copyrights referred to in this presentation may be listed without the TM, SM © or ® symbols, but we will assert, to the fullest extent under applicable law, the rights of the applicable owners, if any, to these trademarks, service marks, trade names and copyrights. Disclaimer and Forward-Looking Statements
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3 Upcoming Catalysts and a Foundation for Success • Varegacestat, an oral, once-daily gamma secretase inhibitor for the treatment of desmoid tumors, with Phase 3 topline data expected before the end of 2025 • IM-1021, a ROR1 ADC, with objective responses observed in B-cell lymphoma patients at multiple dose levels • HC74, a proprietary TOP1i ADC payload with best-in-class potential • Three novel ADCs against solid tumor targets with ongoing IND-enabling studies to support 2026 INDs • IM-3050, a FAP radiotherapy, with Phase 1 initiation expected in early 2026 • Experienced, successful leadership team • Cash runway expected to extend into 2027 Long-Term Corporate Vision • Develop differentiated ADCs with a focus on first-in-class targets • Robust internal discovery efforts, with dozens of novel targets under evaluation and potential for 2+ INDs per year • Additional platform and pipeline expansion driven by disciplined business development and M&A • Efficient clinical development • Strong investor syndicate supportive of corporate vision • Well-positioned for corporate partnering Establishing a Premier Targeted Oncology Company
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4 Management Team with a Demonstrated Track Record of Success • Chief Executive Officer and Founder, Seagen (1998-2022) • Grew company to $2B+ revenue (2022) leading to $43B acquisition • Led development of 4 FDA-approved therapeutics • Raised over $1B in public and private capital • Oversaw acquisition and integration of Cascadian Therapeutics • Generated >$3B in partnership and licensing revenue Clay Siegall, Ph.D. PRESIDENT & CHIEF EXECUTIVE OFFICER Sandra Stoneman CHIEF LEGAL OFFICER Jack Higgins, Ph.D. CHIEF SCIENTIFIC OFFICER Max Rosett CHIEF FINANCIAL OFFICER Bob Lechleider, M.D. CHIEF MEDICAL OFFICER Kinney Horn CHIEF BUSINESS OFFICER Phil Tsai CHIEF TECHNICAL OFFICER Roee Shahar EVP, COMMERCIAL
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5 Pipeline Overview Candidate Mechanism of Action Discovery Preclinical Phase 1 Phase 2 Phase 3 Next Anticipated Milestone Varegacestat (Formerly AL102) Gamma Secretase Inhibitor Phase 3 Topline 2H25 IM-1021 ROR1 ADC Initial Lymphoma Data 2026 IM-3050 FAP RLT First Patient In Early 2026 IM-1617 ADC (Undisclosed Target) IND Submission 2026 IM-1340 ADC (Undisclosed Target) IND Submission 2026 IM-1335 ADC (Undisclosed Target) IND Submission 2026 Additional ADCs ADC (Undisclosed Target) Candidate Nomination
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6 Varegacestat Phase 3 Oral, Once-Daily Gamma Secretase Inhibitor
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7 Desmoid Tumors Are Debilitating, Painful, and Aggressive • Painful soft tissue tumors that can lead to serious disability when left untreated • Highest incidence in young adults, with women at greater risk than men • Until 2023, no approved systemic therapy; local therapies are debilitating and have a high risk of recurrence • Reversing tumor growth, alleviating pain, and improving function are key goals of therapeutic intervention Varegacestat is a Potent Gamma Secretase Inhibitor (GSI) • GSIs block the NOTCH pathway, which is believed to contribute to the growth of desmoid tumors • Varegacestat is a once-daily oral gamma secretase inhibitor currently under investigation in the Phase 3 RINGSIDE trial • OGSIVEO (nirogacestat), a GSI, was approved in November 2023 for treatment of desmoid tumors • Significant growth potential for GSIs Varegacestat May Address Substantial Unmet Patient Need in Desmoid Tumors 1. Gounder 2023 doi: 10.1007/s11136-023-03445-7 2. Tsukamoto 2022 doi: 10.1007/s12306-022-00738-x 3. Analyst consensus as of January 2025 ~5,500-7,500 Actively managed patients in the US2 GSIs Surgery Medical Management Active Surveillance U S D E S M O I D P A T I E N T S 2025 Consensus Estimated Revenue3 $356 M USD
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8 Varegacestat Data With Daily Dosing Shows Increased Response Compared to Nirogacestat Across All Measures • Varegacestat is being evaluated as an oral, once-daily GSI for the treatment of desmoid tumors • Phase 2 RINGSIDE Part A data has shown deep, durable responses and an opportunity to establish new standard of care, if approved • RINGSIDE Part A evaluated 3 dose levels with a response rate of 64% in 1.2mg QD arm (n=14) and 55% overall (n=42) • Reduced T2 imaging suggests reduced cellularity • Safety profile consistent with GSI class • Phase 3 RINGSIDE Part B trial fully enrolled with topline expected in second half of 2025 ORR by RECIST 75% -88% -85% 44% -59% -55% N=12 N=61 N=12 N=53 N=12 N=66 TumorVolume (median best, evaluable) T2 Imaging (median best, evaluable) 64% 41% N=14 N=70 Evaluable ITT Varegacestat 1.2mg QD1 Median ToT 16.6 months Nirogacestat 150mg BID2,3 Median ToT 20.6 months FOR ILLUSTRATIVE PURPOSES ONLY: no head -to-head clinical trial has been conducted evaluating varegacestat against nirogacestat or other candidates or products. Differences exist between trial designs and subject characteristics, and strong caution should be exercised when comparing data across unrelated studies. 1. Kasper B et al., ESMO Congress 2024_1766P (Cutoff Date – April 10, 2024) One patient previously reported as PR at ESMO subsequently progressed prior to response confirmation. 2. Gounder M et al., NEJM 2023, 388:898 3. Alcindor T., et al., ASCO Annual Meeting 2023, Abstract #11514 Evaluable Population
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9 Selected Phase 3 Dose of 1.2 mg Daily Shows Rapid Reduction in Tumor Burden by Multiple Measures Phase 2 RINGSIDE Part A Data (Evaluable Patients) Source: Kasper B et al., ESMO Congress 2024_1766P (Cutoff Date – April 10, 2024) One patient previously reported as PR at ESMO subsequently progressed prior to response confirmation. *All patients received 1.2 mg once daily in the OLE. | #Number of patients in each dose arm decreases at the later time point s
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10 Safety in Phase 2 Portion of RINGSIDE is consistent with GSI class FOR ILLUSTRATIVE PURPOSES ONLY: no head-to-head clinical trial has been conducted evaluating varegacestat against nirogacestat o r other candidates or products. Differences exist between trial designs and subject characteristics, and strong caution shoul d be exercised when comparing data across unrelated studies. 1. Kasper B et al., ESMO Congress 2023_1929P (Cutoff Date – July 5, 2023) 2. Gounder M et al., NEJM 2023, 388:898 3. Alcindor T., et al., ASCO Annual Meeting 2023, Abstract #11514 Evaluable Population Any Grade Grade ≥3 Any Grade Grade ≥3 Diarrhoea 13 (92.8) 2 (14.3) 58 (84) 11 (16) Nausea 8 (57.1) – 37 (54) 1 (1) Fatigue 7 (50) – 35 (51) 2 (3) Alopecia 7 (50) – 13 (19) – Dry skin 7 (50) – 11 (16) – Stomatitis 7 (50) 1 (7.1) 20 (29) 3 (4) Dermatitis acneiform 6 (42.9) – 15 (22) – Dry mouth 6 (42.9) – NR NR Hypophosphatemia 6 (42.9) – 29 (42) 2 (3) Rash maculo-papular 5 (35.7) – 22 (32) 4 (6) Aspartate aminostransferase increased 4 (28.6) – 11 (16) – Months on the study (mean, range), months 16.6 (1-21.6) 20.6 (0.3 – 33.6) Ovarian dysfunction in pre-menopausal women: 5/9 (55.6%) with varegacestat in 1.2 mg QD arm versus 27/36 (75.0%) in nirogacestat DeFi Study Study Population, n(%) Varegacestat, 1.2mg QD, (n=14) Nirogacestat 150mg BID (n=69)
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11 RINGSIDE Phase 3: Evaluating Safety and Efficacy in Progressing Desmoid Tumors Crossover has no observed impact on statistical analysis of primary endpoint Key Inclusion Criteria • Participating in Part B and were noted to have progressive disease by central review • Still on study after completion of Part B Endpoints • Primary: Safety • Secondary: PFS, ORR & DOR by BICR, PROs • Exploratory: PK Phase 3 Open Label Extension (OLE) Key Inclusion Criteria • Relapsed/refractory or treatment- naïve, with PD (per RECIST) in last 12 months • Age ≥12 • Measurable Lesion or MRI or CT Endpoints • Primary: PFS • Secondary: ORR & DOR by BICR, PROs, Safety • Exploratory: MRI T1 & T2, ORR & DOR by investigator, PK, Biomarkers Topline Data Expected Second Half 2025 Varegacestat 1.2 mg once daily OLE (Varegacestat 1.2 mg once daily) Placebo Phase 3 (N=156) Randomized Double-Blind Placebo Controlled
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12 IM-1021 ROR1 ADC
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13 ROR1: Attractive ADC Target in Both Liquid and Solid Tumors ROR1 • Receptor with oncofetal expression pattern, including little or no normal tissue expression1 • Expression on solid and liquid tumors Zilovertamab vedotin (MK-2140) • Monotherapy activity in B-cell lymphomas • Observed toxicities at 2.5 mg/kg monotherapy; 80% grade 3-4 AE in Waveline-006 • 15/15 CRs at 1.75 mg/kg dose level in 1L DLBCL when combined with R-CHP • Randomized Ph3 in 1L DLBCL underway • Discontinued for solid tumors MK-2140 Monotherapy Demonstrates Potential of ROR1 in B-Cell Lymphoma2 19% 15% 28% 5% 14% 13% 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% DLBCL, 2.25 mg/kg (Waveline-004) DLBCL, 2.5 mg/kg (Waveline-004) Mantle Cell Lymphoma 2.5 mg/kg (Waveline-006) ORR PR CR 1. Hojjat-Farsangi M, Moshfegh A, Daneshmanesh AH, Khan AS, Mikaelsson E, Osterborg A, Mellstedt H. The receptor tyrosine kinase ROR1--an oncofetal antigen for targeted cancer therapy. Semin Cancer Biol. 2014 Dec;29:21 -31. doi: 10.1016/j.semcancer.2014.07.005. Epub 2014 Jul 25. PMID: 25068995 2. https://doi.org/10.1182/blood-2024-201522 Waveline-004, 2.25 mg / kg: n=37 Waveline-004, 2.5 mg / kg: n=130 Waveline-006, 2.5 mg / kg: n=40
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14 IM-1021: Potential Best-in-Class ROR1 ADC Designed for Activity in Liquid and Solid Tumors 1. Starting dose is 2 mg/kg of adjusted ideal bodyweight (AIBW) 2. Data sources: TCGA data (solid tumors and DLBCL) from UCSC X ena, version 2016-09-03. Blueprint data (MCL and CLL) from the Blueprint consortium, version 20160816. IM-1021 Design • Antibody selected for ADC-specific properties • Proprietary HC74 payload may enable efficacy in lymphoma and solid tumors • Supports DAR 8 format • Enhanced bystander effect • Favorable therapeutic index Development Status • Phase 1 trial ongoing, with third dose level dosed as of August 2025 • Dose escalation includes B-cell lymphoma and solid tumor patients • Clinical starting dose of 2 mg/kg1 similar to MK- 2140 recommended phase 2 dose • Objective responses observed in B-cell lymphoma patients at multiple doses ROR1 Expression by RNA2 DLBCL TNBC NSCLC, Adeno Ovarian Sarcoma Mesothelioma MCL CLL
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15 ADCs Containing TOP1 Inhibitors Achieve Higher DAR, Allowing for Increased Payload Delivery ADCs with TOP1i Payloads Achieve Higher Clinical Doses than ADCs with Microtubule Inhibitor Payloads IM-1021’s Payload, HC74, May Allow for Higher Clinical Dose, Increasing Therapeutic Index 1.8 1.25 1.8 3.6 2.5 5.4 10 0 2 4 6 8 10 12 Polivy® Padcev® Adcetris® Kadcyla® MK-2140 Enhertu® Trodelvy® Clinical dose (mg/kg) Clinical Doses of Selected ADCs1 TOP1 Inhibitor Microtubule Inhibitor 3.5 3.8 4 3.5 4 8 7.6 0 1 2 3 4 5 6 7 8 9 Polivy® Padcev® Adcetris® Kadcyla® MK-2140 Enhertu® Trodelvy® DAR Drug-Antibody Ratios of Selected ADCs2 TOP1 Inhibitor Microtubule Inhibitor Payload MOA 1. Respective drug labels or FDA guidance 2. Tong JTW, Harris PWR, Brimble MA, Kavianinia I. An Insight into FDA Approved Antibody-Drug Conjugates for Cancer Therapy. Molecules. 2021 Sep 27;26(19):5847. doi: 10.3390/molecules26195847. PMID: 34641391; PMCID: PMC8510272. 3. Cortés et. al. N Engl J Med (2022); 386:1143-1154 HC74 Shows Favorable Tolerability Consistent with Class Payload MOA
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16 IM-1021 Achieves Tumor Regressions in Jeko-1 MCL Model IM-1021 Achieves 8/8 CRs at 2.5 mg/kg in NSCLC PDX Model IM-1021 Preclinical Activity Supports Development in Lymphoma and Solid Tumors 0 500 1000 1500 2000 2500 0 3 7 10 14 17 Mean Tumor Volume (mm3) Days Post Treatment Start Vehicle IM-1021 2.5 mpk qw*3 IM-1021 5 mpk qw*3 MK-2140 2.5 mpk qw*3 MK-2140 5 mpk qw*3 0 500 1,000 1,500 2,000 2,500 3,000 0 3 7 10 14 17 21 24 28 Mean Tumor Volume (mm3) Days Post Treatment Start Vehicle IM-1021 2.5 mpk qw*3
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17 Population includes: • R/R B-cell lymphoma • R/R solid tumors Dose escalation design: • mTPI-2 adaptive design • Expand 2 or more doses • Required minimum representation of lymphoma and solid tumor in Part A before expansion • Optional cohorts to test split dosing Clinical Development Plan: Rapid Establishment of PoC To Enable Pivotal Studies Across Multiple Indications DL1: 2 mg/kg AIBW DL2 DL3 DL4 DL5 Part A: Dose Escalation Population includes: • Up to 3 indication- specific expansion cohorts (B1, B2, B3) Potential indications include those listed in Inclusion 4.a Dose expansion design: • Per cohort, randomize 1:1 to 2 regimens (DL-X, DL-Y) • Per indication-specific cohort Part B: Indication-Specific Dose Expansion DL-Y DL-XIndication Cohort B1 DL-Y DL-X DL-Y DL-X Indication Cohort B2 Indication Cohort B3 AIBW: Adjusted Ideal Body Weight DL6 DL7 B-cell Lymphomas • DLBCL • Mantle Cell • Follicular • SLL Solid Tumors • NSCLC (non-squam) • TNBC • Ovarian • Mesothelioma • Liposarcoma • Pancreatic Patients dosed through DL3 as of August 2025
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18 ADC Discovery Strategy
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19 • ADC-focused discovery team with deep experience in ADC target selection, design, and optimization • Technical operations leadership with a track record of delivering drug supply and high-quality IND/BLA submissions • Seasoned development team whose members spearheaded FDA-approved ADCs Immunome’s Experienced Team is Positioned to Develop the Next Generation of Transformative ADCs Clear Strategy and the Experience to Execute Efficient Translation & Early Development • Well-designed IND-enabling studies to support favorable first-in-human doses • Phase 1 studies designed for rapid transition to registrational studies Technical Operations Excellence • Scalable, transferable manufacturing processes Research Capabilities • Numerous programs in lead optimization or preclinical development • Potential for 2+ INDs per year Exceptional ADC Expertise
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20 Rigorous Target Validation and Optimized ADC Design Unlocks New ADC Targets • Targets: Prioritize targets with compelling biology and no approved ADCs • Antibodies: Optimize and evaluate as ADCs • Technology: Proprietary HC74 TOP1i payload designed to achieve wide therapeutic index while escaping chemo resistance and generating robust bystander effect • Capabilities: High-throughput conjugation and screening supports empirical evaluation of hundreds of ADCs 10 Targets Account for 50% of Active Clinical ADC Programs1 36 28 23 18 11 10 17 17 16 9 Active Clinical ADC Programs Approved ADC No Approved ADC Majority of ADC Activity is Concentrated in a Small Number of Targets Immunome ADC Strategy 1. Immunome analysis of Hanson Wade Beacon ADC data as of November 2025
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21 Proprietary HC74 Payload Designed to be Best-in-Class TOP1i Shown to Overcome Multiple Resistance Mechanisms Design Goal HC74 ADCs DXd ADCs Overcome Payload Resistance Low efflux potential overcomes payload resistance mediated by transporters like ABCC1 and ABCB1 X High efflux potential leads to primary and acquired payload resistance Overcome Target-Mediated Resistance High permeability increases cytotoxicity and bystander activity, also killing target-negative tumor cells X Low permeability leads to poor bystander activity Enhanced Tumor Exposure Greater linker-antibody stability increases amount of payload delivered to tumor X Linker-antibody deconjugation reduces payload delivery to tumor HC74 ADCs have potential for greater frequency and duration of patient benefit
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22 HC74 TOP1i Payload and ADCs Shows Superior Properties to DXd Enhanced stability leads to increased payload delivery Payload Loss at Day 7 DXd ADC 36% HC74 ADC 18% Increased permeability supports superior bystander effect Payload Permeability2 DXd 2 HC74 9 Lower efflux ratio may overcome chemo-resistance Payload Efflux1 DXd 79 HC74 10 HC74 In Vitro Cytotoxicity4HC74 In Vitro Cytotoxicity3 1. Caco-2 efflux ratio; 2. MDCK Papp (x10-6 cm/s); 3. IC50 values of HC74 and DXd, with or without KO143 (pan-efflux inhibitor) in parental or engineered NCI-N87 cells overexpressing ABCC1 or ABCB1 4. In vitro bystander activity of HC74 and DXd ADCs in a co-culture model using NCI-H446 cells engineered to express either TROP2 or luciferase. 5. Drug-Antibody-Ratio (DAR) as measured by LC-MS. 0 2 4 6 8 10 12 14 HC74 Dxd Dxd + Inhibitor IC50 (nM) N87 N87 - ABCB1+ 0 2 4 6 8 0 2 4 6 8 Time (Day) DAR IgG1-HC74 IgG1-DXd 0% TROP2+ 20% TROP2+ 100% TROP2+ 0 50 100 % viability Trop2-HC74 Trop2-DXd HC74 ADC Average DAR5 % Viability
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23 High ABCB1 Expression Correlates with Lower ORR and PFS in HER2+ CRC Patients Treated With T-DXd1 Sensitivity to Efflux Meaningfully Limits the Clinical Efficacy of Existing TOP1 ADCs Baseline ABCB1 Expression ORR, % P value PFS, months P value < Median 47.1 0.003 8.1 < 0.001≥ Median 17.6 4.2 Baseline ABCC1 Expression Median OS, months P value Top Quartile 14.2 0.0021 Quartiles 1-3 17.8 1. Sienna et al. Exploratory biomarker analysis of trastuzumab deruxtecan (T-DXd) treatment for HER2-positive (HER2+) metastatic colorectal cancer (mCRC) in DESTINY-CRC02. AACR, 2025. 2. Sledge et al. Mechanisms of Resistance to Trastuzumab Deruxtecan in Breast Cancer Elucidated by Multi -omic Molecular Profiling. SABCS, 2024. High ABCC1 Expression is Associated with Shorter OS in Breast Cancer Patients Treated with T-DXd2 ABCC1 Expression Q1-Q3 ABCC1 Expression Q4
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24 HC74 ADCs Overcome Primary Resistance to T-DXd or Irinotecan in ABCB1+ CRC Tumors HC74 ADC Shows Activity in a CRC Model Refractory to Other TOP1i Agents Source: Zhang et al., AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2025_A111. "Colorectal cancer (CRC) mRNA values for ABCB1 are from UCSC Xena TCGA-TARGET-GTEx re-analysis, version 2016-09-03 (Vivian et al. Nat Biotech, 2017). HCT-15 mRNA data were generated internally and represent the median of 3 replicates." 0 7 14 21 28 35 42 49 0 500 1000 1500 2000 Days Post Treatment Start Tumor Volume (mm3) ▲ ▲ ▲ ▲ Vehicle: T-DXd(8), 10mg/kg: T-HC74(8), 10mg/kg: Re-randomized at ~600 mm3 Post T-DXd Failure HCT-15 0 7 14 21 28 35 42 0 500 1000 1500 2000 Days Post Treatment Start Tumor Volume (mm3) ▲ ▲ ▲ ▲ Vehicle: Irinotecan, 15mg/kg: T-HC74(8), 10mg/kg: ▲ ▲ ▲ Post Irinotecan Failure HCT-15 Re-randomized at ~600 mm3 ABCB1 Expression HCT-15 HCT-15
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25 HC74 Overcomes Acquired DXd Resistance NCI-N87R Tumor Cells Overexpress ABCC1 Immunome's HC74 Payload Demonstrates Ability to Overcome Acquired DXd Resistance Source: Zhang et al., AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2025_A111 NCI-N87R (DXd-R Gastric) 0 7 14 21 28 0 200 400 600 800 1000 1200 Days Post Treatment Start Tumor Volume (mm3) Vehicle T-DXd(8), 3mg/kg T-HC74(8), 3mg/kg
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26 HC74 ADC Demonstrates Durable Response in NSCLC Model of Tumor Heterogeneity HC74 ADC Demonstrates Superior Bystander Activity vs. DXd ADC Potential for Greater HC74 Efficacy in Target Heterogenous Tumors NCI-H292 Bystander Model (75% TROP2+; 25% TROP2 KO) 0 5 10 15 20 25 30 35 40 45 0 500 1000 1500 2000 Days Post Treatment Start Tumor Volume (mm3) Vehicle TROP2-DXd, 5mg/kg, SD TROP2-HC74, 5mg/kg, SD Isotype-HC74, 5mg/kg, SD Clonal Preclinical Models Do Not Capture Expression Heterogeneity Source: Zhang et al., AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2025_A111 Antigen-positive cells Antigen-negative cells ADC
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27 Novel ADC Development Candidates Three ADCs Against Undisclosed Targets Expressed in Solid Tumors
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28 Target Properties • Tumor Expression: Major solid tumors including colorectal, NSCLC, breast, and ovarian • Non-Obvious Target: Overlooked due to moderate levels of cell surface expression; however, rapid recycling and intracellular reservoir support efficient payload delivery • Tumor Biology: Receptor tyrosine kinase that promotes tumor cell survival and mediates immune cell exclusion, providing potential for secondary mechanism of action • IM-1617’s target not shared with any known ADC program IM-1617’s Target is Expressed in Solid Tumor Indications with Significant Unmet Need IM-1617 Pursues a Novel ADC Target with Multi-Indication Solid Tumor Potential Cervical Renal Head & neck Thyroid Esophageal Melanoma Breast Colorectal DLBCL NSCLC, Squamous NSCLC, Adeno Urothelial CNS/PNS Gastric Hepatocellular Ovarian Pancreatic Prostate Uterine Sarcoma Testicular0 25 50 75 100 IM-1617 tumor IHC IHC score Negative Low Moderate High
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29 In Vivo Activity IM-1617 Design Considerations • Antibody selected for attributes that drive tumor binding while minimizing normal tissue binding • Proprietary HC74 TOP1i payload for broad use in solid tumors Tolerability • Initial NHP study found a HNSTD of 40 mg/kg, indicating robust therapeutic window IM-1617 is a Potential First-in-Class ADC With Robust Preclinical Activity IND Expected in 2026 Preclinical Activity: Regressions achieved after a single clinically relevant dose in tumor models derived from CRC, NSCLC, melanoma, esophageal, and other carcinomas 0 5 10 15 20 25 30 35 0 1000 2000 3000 Esophageal (KYSE30) Days Post Treatment Start Mean Tumor Volume (mm3) Vehicle Isotype ADC, 5 mg/kg IM-1617, 2.5 mg/kg IM-1617, 5 mg/kg 0 5 10 15 20 25 30 35 0 1000 2000 3000 Colorectal (HCT116) Days Post Treatment Start Mean Tumor Volume (mm3) Vehicle Isotype ADC, 5 mg/kg IM-1617, 2.5 mg/kg IM-1617, 5 mg/kg
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30 IM-1340’s Target is Expressed in Neuroendocrine Tumors, Lung, and Prostate Identifying a Unique Expression Profile • Tumor Expression: Spans neuroendocrine tumors and carcinomas • Tumor Biology: Target known to promote tumor growth by accelerating proliferation, cell cycle progression, and migration of cancer cells • Endocytic Receptor: Transport receptor for endolysomal protease, leading to favorable internalization dynamics • Limited normal tissue expression • IM-1340’s target not shared with any known program IM-1340 is a Potential First-in-Class ADC Against a Novel Solid Tumor Receptor NET, multiple Endometrial Pancreatic Lung, SCLC Ovarian Prostate, AD Gastric, AD Renal, clear cell Colon, AD NSCLC, AD Breast, TN Cervical, SCC Gastric, GEJ Esophageal, AD NSCLC, SCC Esophageal, SCC Melanoma 0 25 50 75 100 IHC Score (Percent of Total) Negative Low Moderate High
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31 IM-1340 Design Considerations • High affinity antibody selected to drive efficacy • Proprietary HC74 TOP1i payload selected given sensitivity of NET and other solid tumors to mechanism of action Tolerability • Initial NHP study found a HNSTD of 40 mg/kg, indicating robust therapeutic window Preclinical Activity: Regression achieved after a single dose of 1 mg/kg in in vivo tumor models including pancreatic, prostate, SCLC, and NSCLC In Vivo Activity IM-1340 Shows Robust Efficacy in a Range of Models IND Expected in 2026 0 5 10 15 20 25 30 35 0 500 1000 1500 2000 SCLC (NCI-H1105) Days Post Treatment Start Mean Tumor Volume (mm3) Vehicle Isotype ADC, 5 mg/kg IM-1340, 1 mg/kg IM-1340, 2.5 mg/kg IM-1340, 5 mg/kg 0 5 10 15 20 25 30 0 500 1000 1500 2000 2500 NSCLC (CALU6) Mean Tumor Volume (mm3) Vehicle Isotype ADC, 5 mg/kg IM-1340, 2.5 mg/kg IM-1340, 5 mg/kg
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32 Revisiting a Target with Demonstrated Clinical Efficacy • IM-1335 shares a target with an ADC that showed clinical activity but was ultimately discontinued • Immunome identified limitations that contributed to the failure of the prior ADC and believes it fixed them with IM-1335: • Antibody engineering to improve PK and tumor biodistribution profile • Optimized linker to enhance stability for on-target activity • Incorporated HC74 TOP1i payload to match drug sensitivity of top indications • Additional information expected to be disclosed at a future date IM-1335: ADC Optimization Driven by Understanding Biology of a Known Target In Vivo Activity 0 5 10 15 20 0 500 1000 1500 2000 Solid Tumor Indication Mean Tumor Volume (mm3) IM-1335, 5 mg/kg IM-1335, 2.5 mg/kg Isotype ADC, 5 mg/kg Vehicle IND Expected in 2026
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33 In Vivo Preclinical Efficacy for Three Additional Candidates Additional Discovery-Stage Candidates Demonstrate Solid Tumor Activity • Immunome has generated in vivo data for over a dozen distinct targets, with multiple programs currently undergoing lead optimization • Tumor regressions achieved at doses of 5 mg/kg or lower in major indications including • Colorectal cancer • Lung Cancer • Breast Cancer • Ovarian Cancer • Additional candidates expected to be advanced to development as appropriate • Potential opportunities for partnerships and non-dilutive financing 0 5 10 15 20 25 0 500 1000 1500 2000 2500 3000 SCLC (NCI-H446) Days Post Treatment Start Mean Tumor Volume (mm3) ADC-U7, 5 mg/kg Isotype ADC, 5 mg/kg Vehicle 0 5 10 15 20 25 0 500 1000 1500 2000 2500 Colorectal (SW480) Days Post Treatment Start Mean Tumor Volume (mm3) Vehicle Isotype ADC, 2.5 mg/kg ADC-U9, 2.5 mg/kg 0 5 10 15 20 25 30 0 500 1000 1500 2000 2500 Colorectal (HT-29) Days Post Treatment Start Mean Tumor Volume (mm3) ADC-U8, 5 mg/kg ADC-U8, 2.5 mg/kg Isotype ADC, 5 mg/kg Vehicle
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34 IM-3050 FAP-Targeted Radioligand Therapy
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35 Fibroblast Activation Protein (FAP) is a cell surface protease with low expression in normal tissue • FAP is overexpressed on cancer-associated fibroblasts, the most common tumor stromal cell, with expression in 75% of solid tumors • FAP-Lu radioligand therapy delivers radioactive 177Lu directly to FAP-expressing cells, with bystander effect targeting tumor cells • RLT approach expected to overcome limitations that make FAP unsuitable for ADCs (poor internalization and low expression on tumor cells) FAP imaging shows high expression across 15 distinct tumor types FAP Is a Promising RLT Target with Pan-Cancer Potential Source: Kratochwil C, Flechsig P, Lindner T, et al. 68Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer. J Nucl Med. 2019;60(6):801-805.
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36 Immunome has systematically selected a ligand, linker, albumin binding domain, and payload to optimize: • Binding and specificity • Stability • Pharmacokinetics • Tumor absorbed dose • Efficacy • Tolerability Immunome 177Lu-FAP Candidates are Rationally Designed and Systematically Screened Immunome Approach Example Structure: FAP binding and specificity optimized Proven structure used by Pluvicto and Lutathera to deliver Lu-177 isotope Albumin binding domain selected to maximize tumor retention Optimized linker reduces non-specific uptake Optimized ligand potentially leads to: • Increased tumor uptake and retention • Superior efficacy • Stability and ease of manufacture Incorporating albumin binder potentially extends circulating half-life and increases tumor residence time, leading to superior tumor absorbed dose in vivo FAP Ligand Linker Chelator Albumin Binder
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37 IM-3050 is a 177Lu-FAP Candidate with Best-in-Class Potential Tumor Regression in U87MG Model No Weight Loss Observed Potential Best-in-Class Characteristics Sub-nanomolar affinity High specificity Radiostability Superior tumor retention and tumor absorbed dose in vivo Preclinical activity and tolerability DEVELOPMENT STATUS: Phase 1 initiation expected in early 2026 In Vivo Radiotherapy Studies GLP/GMP Manufacturing IND cleared in 2Q25 ✓ Clinical Formulation Development ✓ In vivo data show single dose antitumor activity and tolerability 0 5 10 15 20 25 80 90 100 110 120 Day Relative body weight (% of pretreatment) Vehicle IM-3050, 150 mCi IM-3050, 500 mCi 0 5 10 15 20 25 0 200 400 600 800 1000 1200 Day Tumor Volume (% of pretreatment) Vehicle IM-3050, 150 mCi IM-3050, 500 mCi ✓ ✓
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38 • Fully enrolled Phase 3 trial for varegacestat with topline data expected before the end of 2025 • Clinical and IND-stage programs with best-in-class or first-in-class potential: • IM-1021: ROR1 ADC with objective responses observed at multiple dose levels in B-cell lymphoma patients • IM-3050: FAP RLT with Phase 1 initiation expected in early 2026 • HC74, a proprietary TOP1i ADC payload with best-in-class potential • Three novel solid-tumor targeted ADCs with planned 2026 INDs: IM-1617, IM-1335, and IM-1340 • Cash runway expected to extend into 2027 Building the Foundation of the Next Transformative ADC Company