Slides
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Immunome Corporate PresentationJanuary 2025
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2 DisclosuresFor the 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 anyperson 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 StatementsStatements 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 theseterms, 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 ourplatform and pipeline and our approach and strategy related to the platform and pipeline; assessments of the clinical efficacy, best-in-class potential, and potential commercial success of our AL102 program; thepotential 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 ourstrategic 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 one or more of ourcurrent or future programs and product candidates and other anticipated milestones; our expected cash runway; our ability to expand our platform and establish a broad pipeline and advance it through efficient clinicaldevelopment decisions; our intention to continue expanding our pipeline through strategic transactions; our intent 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 beincorrect; 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 realizethe 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 pre-clinical data may not be predictive of clinical data; the risk that Immunome’s product candidates and development candidates fail to achieve their intended endpoints; the reliance on Immunome’s management; theprior experience and successes of Immunome’s management team not being indicative of any future success; uncertainties related to Immunome’s capital requirements and Immunome’s expected cash runway;Immunome’s ability to grow and successfully execute on its business plan, including the development and commercialization of its pipeline and integration of newly acquired assets; and other risks and uncertaintiesindicated from time to time described in Immunome’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, filed with the SEC on November 13, 2024, and in Immunome’s other filings with theSEC. Except as required by law, Immunome assumes no obligation and does not intend to update any forward-looking statements included in this presentation.Product CandidatesIn 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 othergovernmental 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 DataIn 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 orto 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 fromthird-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 theindicated information. We have not independently verified the information provided by the third-party sources.TrademarksThis 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, servicemarks, 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, ifany, to these trademarks, service marks, trade names and copyrights. Disclaimer and Forward-Looking Statements
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3 Anticipated 2025 Catalysts and a Foundation for Long-Term Success•Varegacestat (formerly AL102), an oral, once-daily gamma secretase inhibitor for the treatment of desmoid tumors, with Phase 3 topline data expected in second half of 2025•IM-1021, a ROR1 ADC, with Phase 1 initiation planned 1Q25 •IM-3050, a FAP radiotherapy, with IND submission expected 1Q25•Three novel ADCs against solid tumor targets entering IND-enabling studies •Experienced, successful leadership team with record of designing, developing, and commercializing ADCs and other targeted oncology therapies•Cash runway expected to extend into 2026Anticipated 2025 Catalysts and a Foundation for Long-Term Success•Varegacestat (formerly AL102), an oral, once-daily gamma secretase inhibitor for the treatment of desmoid tumors, with Phase 3 topline data expected in second half of 2025•IM-1021, a ROR1 ADC, with Phase 1 initiation planned 1Q25 •IM-3050, a FAP radiotherapy, with IND submission expected 1Q25•Three novel ADCs against solid tumor targets entering IND-enabling studies •Experienced, successful leadership team with record of designing, developing, and commercializing ADCs and other targeted oncology therapies•Cash runway expected to extend into 2026Long-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 up to 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 partneringLong-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 up to 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 partneringEstablishing 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 StonemanCHIEF LEGAL OFFICER Bruce Turner, M.D., Ph.D.CHIEF STRATEGY OFFICER Jack Higgins, Ph.D.CHIEF SCIENTIFIC OFFICER Max RosettCHIEF FINANCIAL OFFICER Bob Lechleider, M.D.CHIEF MEDICAL OFFICER Kinney HornCHIEF BUSINESS OFFICER Phil TsaiCHIEF TECHNICAL OFFICER Roee ShaharEVP, COMMERCIAL
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5 4 Antibodies20244 Antibodies2024Recent Business Development Activity Expanded Pipeline With Moderate Investment 28 Antibodies202428 Antibodies2024PRECLINICALCLINICALVaregacestat (AL102) and AL1012024Varegacestat (AL102) and AL1012024 RECENT TRANSACTIONS IM-1021 Program & ADC Platform2024IM-1021 Program & ADC Platform2024 ANTIBODIES 2024202420242024 20252025
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6 Pipeline OverviewNext Anticipated MilestonePhase 3Phase 2Phase 1PreclinicalDiscoveryMechanism of ActionCandidatePhase 3 Topline2H25Gamma Secretase InhibitorVaregacestat(Formerly AL102)Initiate Enrollment1Q25ROR1 ADCIM-1021IND Submission1Q25FAP RLTIM-3050IND SubmissionADC (Undisclosed Target)IM-1617IND SubmissionADC (Undisclosed Target)IM-1340IND SubmissionADC (Undisclosed Target)IM-1335Candidate NominationADC (Undisclosed Target)Additional ADCs
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7 Varegacestat (Formerly AL102)Phase 3 Oral, Once-Daily Gamma Secretase Inhibitor
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8 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 interventionDesmoid 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 interventionVaregacestat is a Potent Gamma Secretase Inhibitor•Gamma secretase inhibitors (GSIs) block the NOTCH pathway, a driver of desmoid tumors•Varegacestat is a once-daily oral gamma secretase inhibitor currently under evaluation in Phase 3 RINGSIDE trial •OGSIVEO (nirogacestat) is a GSI that was approved in November 2023 for treatment of desmoid tumors•Significant growth potential for gamma secretase inhibitorsVaregacestat is a Potent Gamma Secretase Inhibitor•Gamma secretase inhibitors (GSIs) block the NOTCH pathway, a driver of desmoid tumors•Varegacestat is a once-daily oral gamma secretase inhibitor currently under evaluation in Phase 3 RINGSIDE trial •OGSIVEO (nirogacestat) is a GSI that was approved in November 2023 for treatment of desmoid tumors•Significant growth potential for gamma secretase inhibitorsVaregacestat (formerly AL102) 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 and Springworks analysis~5,500-7,500Actively managed patients in the US2 2025 GSI Consensus Estimated US Revenue$320 M USD
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9 Varegacestat (AL102) 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•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•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•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 2025ORR by RECIST75%-88%-85%44%-59%-55%N=12N=61N=12N=53N=12N=66Tumor Volume(median best, evaluable)T2 Imaging(median best, evaluable)64%41%N=14N=70EvaluableITTVaregacestat 1.2mg QD1Median ToT 16.6 monthsNirogacestat 150mg BID2,3Median ToT 20.6 monthsFOR 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 2023_1929P (Cutoff Date – July 5, 2023) 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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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 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 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 Grade ≥3Any GradeGrade ≥3Any Grade11 (16)58 (84)2 (14.3)13 (92.8)Diarrhoea1 (1)37 (54)–8 (57.1)Nausea2 (3)35 (51)–7 (50)Fatigue–13 (19)–7 (50)Alopecia–11 (16)–7 (50)Dry skin3 (4)20 (29)1 (7.1)7 (50)Stomatitis–15 (22)–6 (42.9)Dermatitis acneiformNRNR–6 (42.9)Dry mouth2 (3)29 (42)–6 (42.9)Hypophosphatemia4 (6)22 (32)–5 (35.7)Rash maculo-papular–11 (16)–4 (28.6)Aspartate aminostransferase increased20.6 (0.3 – 33.6)16.6 (1-21.6)Months on the study (mean, range), monthsOvarian dysfunction in pre-menopausal women: 5/9 (55.6%) with Vargecacestat in 1.2 mg QD arm versus 27/36 (75.0%) in Niro DeFi Study Study Population, n(%)Varegacestat (AL102), 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 Endpoints•Primary:Safety•Secondary:PFS, ORR & DOR by BICR, PROs•Exploratory:PKKey Inclusion Criteria•Participating in Part B and were noted to have progressive disease by central review•Still on study after completion of Part BPhase 3Open Label Extension (OLE)Endpoints•Primary:PFS•Secondary:ORR & DOR by BICR, PROs, Safety•Exploratory:MRI T1 & T2, ORR & DOR by investigator, PK, BiomarkersKey Inclusion Criteria•Relapsed/refractory or treatment-naïve, with PD (per RECIST) in last 12 months•Age ≥12•Measurable Lesion or MRI or CTTopline Data Expected Second Half 2025
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12 IM-1021ROR1 ADC
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13 ROR1 Is a Clinically Active ADC Target with Expression in Both Liquid and Solid TumorsROR1•Receptor with oncofetal expression pattern, including little or no normal tissue expression1•Expression on solid and liquid tumorsZilovertamab Vedotin (MK-2140)•ROR1-targeted ADC, acquired by Merck from Velos Bio in $2.75 billion acquisition•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•Discontinued for solid tumorsROR1•Receptor with oncofetal expression pattern, including little or no normal tissue expression1•Expression on solid and liquid tumorsZilovertamab Vedotin (MK-2140)•ROR1-targeted ADC, acquired by Merck from Velos Bio in $2.75 billion acquisition•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•Discontinued for solid tumorsMK-2140 Monotherapy Demonstrates Potential of ROR1 in B-Cell Lymphoma2MK-2140 Monotherapy Demonstrates Potential of ROR1 in B-Cell Lymphoma219%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)ORRPRCR1. 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: 250689952. 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 Design•Antibody optimized for ADC-specific properties•HC74 payload selected for properties that enable efficacy in both lymphoma and solid tumors •Enhanced therapeutic index•DAR8•Bystander effect•Potential combination with MMAE ADCsDevelopment Status•IND cleared in December 2024•Dose escalation will cover solid tumors and B-cell lymphoma•Clinical starting dose similar to MK-2140 recommended phase 2 dose IM-1021 Design•Antibody optimized for ADC-specific properties•HC74 payload selected for properties that enable efficacy in both lymphoma and solid tumors •Enhanced therapeutic index•DAR8•Bystander effect•Potential combination with MMAE ADCsDevelopment Status•IND cleared in December 2024•Dose escalation will cover solid tumors and B-cell lymphoma•Clinical starting dose similar to MK-2140 recommended phase 2 dose IM-1021: Optimized ROR1 ADC with Phase 1 Enrollment Expected 1Q25 050010001500200025000 3 7 10 14 17Mean Tumor Volume (mm3)Days Post Treatment StartIM-1021 Shows Superior Efficacy to MK-2140 in Jeko-1 MCL modelVehicleIM-1021 2.5 mpk qw*3IM-1021 5 mpk qw*3MK-2140 2.5 mpk qw*3MK-2140 5 mpk qw*3
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15 ADCs Containing TOP1 Inhibitors Achieve Higher DAR, Allowing for Increased Payload DeliveryADCs Containing TOP1 Inhibitors Achieve Higher DAR, Allowing for Increased Payload DeliveryADCs with TOP1i Payloads Achieve Higher Clinical Doses than ADCs with Microtubule Inhibitor PayloadsADCs with TOP1i Payloads Achieve Higher Clinical Doses than ADCs with Microtubule Inhibitor PayloadsIM-1021’s Payload, HC74, May Allow for Higher Clinical Dose, Increasing Therapeutic Index 1.81.2523.62.55.410024681012Polivy® Padcev® Tivdak® Kadcyla® MK-2140 Enhertu® Trodelvy®Clinical dose (mg/kg)Clinical Doses of Selected ADCs1TOP1 InhibitorMicrotubule Inhibitor3.53.843.5487.60123456789Polivy® Padcev® Tivdak® Kadcyla® MK-2140 Enhertu® Trodelvy®DARDrug-Antibody Ratios of Selected ADCs2TOP1 InhibitorMicrotubule InhibitorPayload MOA1. 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); 386:1143-1154HC74 Shows Favorable Tolerability Consistent with Class Payload MOA
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16 Significant Solid Tumor Opportunity for IM-1021ROR1 is Expressed in Major Solid Tumor Indications1ROR1 is Expressed in Major Solid Tumor Indications1IM-1021 Achieves Tumor Regressions in TNBC (MDA-MB-468) ModelIM-1021 Achieves Tumor Regressions in TNBC (MDA-MB-468) ModelIM-1021 Achieves 8/8 CR at 2.5 mg/kg in NSCLC PDX ModelIM-1021 Achieves 8/8 CR at 2.5 mg/kg in NSCLC PDX Model0%10%20%30%40%50%60%70%80%90%100%Ovarian (n=144)Colon (n=110)Lung (n=64)Lymphoma (n=58)Skin (n=55)Pancreatic (n=57)Testicular (n=48)Bladder (n=40)Uterus (n=29)Prostate (n=21)Adrenal (n=12)Percent ROR1 PositiveStrongModerateNegative010020030040050060070080090010000 2 6 9 13 16 20 23 27 31 34Mean Tumor Volume (mm3)Days Post Treatment StartVehicleIM-1021 2.5 mpk qw*3IM-1021 5 mpk qw*3MK-2140 2.5 mpk qw*3MK-2140 5 mpk qw*305001,0001,5002,0002,5003,0000 3 7 10 14 17 21 24 28Mean Tumor Volume (mm3)Days Post Treatment StartVehicleIM-1021 2.5 mpk qw*31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509760/
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17 Criteria for selecting pivotal clinical study indications•Compelling Phase 1 clinical outcomes•Significant commercial opportunities•Enhanced outcomes with companion diagnostic•Potential for Accelerated ApprovalCriteria for selecting pivotal clinical study indications•Compelling Phase 1 clinical outcomes•Significant commercial opportunities•Enhanced outcomes with companion diagnostic•Potential for Accelerated ApprovalClinical Development Plan: Rapid Establishment of PoC Followed by Pivotal Studies Across Multiple IndicationsRapid dose escalation in solid tumors and lymphomaRapid dose escalation in solid tumors and lymphomaNon-clinical evaluation of combination therapies, particularly in B-cell malignanciesNon-clinical evaluation of combination therapies, particularly in B-cell malignanciesCompanion diagnostic development and evaluationCompanion diagnostic development and evaluationSolid tumor expansionIndications including NSCLC, breast cancer, and other solid tumorsSolid tumor expansionIndications including NSCLC, breast cancer, and other solid tumorsB-cell malignancy expansionDiffuse large B-cell lymphoma and mantle cell lymphoma B-cell malignancy expansionDiffuse large B-cell lymphoma and mantle cell lymphoma 1. Clinical development plan subject to further refinement and addition or removal of indications.. NSCLC = non-small cell lung cancer
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18 ADC Discovery Strategy
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19 • Deep understanding of target biologyRigorous Target Selection • HC74, Immunome’s proprietary TOP1i, supports novel target strategy• Optimized, proprietary linkersDifferentiated Technology • Prioritize key preclinical experiments to identify best candidatesEfficient DevelopmentImmunome’s Experienced Team is Positioned to Develop the Next Generation of Transformative ADCs Clear Strategy and the Experience to Execute • Executive leadership with proven record of success• ADC-focused discovery team with deep experience in ADC target selection and design• Seasoned development team whose members spearheaded FDA-approved ADCsExceptional ADC Expertise
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20 Immunome’s ADC Discovery Efforts Advanced 3 Novel Candidates into Development in 2024~1000 Targets Screened15+ TargetsEvaluated In Vivo3 Novel Solid Tumor ADCsIND-Enabling Studies OngoingMultiple New ADC Candidates Per Year Expected Differentiated Strategy•Focus on targets that have no approved ADCs and on indications with substantial unmet need•Prioritize definitive preclinical experiments, allowing for financial efficiency and rapid advancement•Extensive expression analysis•Optimize antibody for enhanced internalization and tumor localization•Six additional ADCs currently undergoing lead optimization with development decisions expected in 2025/2026Differentiated Strategy•Focus on targets that have no approved ADCs and on indications with substantial unmet need•Prioritize definitive preclinical experiments, allowing for financial efficiency and rapid advancement•Extensive expression analysis•Optimize antibody for enhanced internalization and tumor localization•Six additional ADCs currently undergoing lead optimization with development decisions expected in 2025/202640+ TargetsEvaluated In Vitro
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21 Top 10 Targets Account for 55% of Active Clinical ADC Programs Top 10 Targets Account for 55% of Active Clinical ADC Programs The Majority of ADC Activity is Concentrated in a Small Number of Targets40241097161512108HER-2 TROP-2 CLDN18.2 B7-H3 EGFRFRαHER-3 Nectin-4 c-MET TFR1 Active Clinical ADC ProgramsApproved ADCNo Approved ADC1.: Immunome Analysis of Beacon ADC data. from Hanson Wade as of September 2024
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22 HC74 retains the validated TOP1 mechanism of action while showing properties superior to DXd•Superior potencymeasured across 89 cell lines •Retained potency in chemo-resistant cell lines•Increased permeability may lead to superior bystander effect•Rapid hepatocyte clearance may improve tolerabilityHC74 retains the validated TOP1 mechanism of action while showing properties superior to DXd•Superior potencymeasured across 89 cell lines •Retained potency in chemo-resistant cell lines•Increased permeability may lead to superior bystander effect•Rapid hepatocyte clearance may improve tolerabilityImmunome’s Proprietary TOP1 Inhibitor, HC74, Supports Development of ADCs for Novel Targets 1.. PAMPA permeability: HC74 8x10-6cm/s DXd: 21*10^-6 cm/s. 2. Vincristine Resistant Cell Line: H69/VCR. Doxorubicin Resistant: H69/AR TOP1 inhibitors are proven ADC payloads•TOP1 inhibitors are DNA-damaging agents•Enhertu, which incorporates the TOP1 inhibitor DXd, validated the TOP1 mechanism of action in ADCs•Approved ADCs with TOP1i payloads generally show greater tolerabilityand achieve higher doses than earlier ADCs TOP1 inhibitors are proven ADC payloads•TOP1 inhibitors are DNA-damaging agents•Enhertu, which incorporates the TOP1 inhibitor DXd, validated the TOP1 mechanism of action in ADCs•Approved ADCs with TOP1i payloads generally show greater tolerabilityand achieve higher doses than earlier ADCs Enhertu(Trastuzumab deruxtecan)n=261Kadcyla(Trastuzumab emtansine) n=263Progression-Free SurvivalPercentage of patients05101520253035HC74 Dxd SN-38IC50 (nM)Relative Potency in H69 Tumor Cell Line VariantsH69Vincristine ResistantDoxorubicin Resistant
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23 Novel ADC Development CandidatesThree ADCs Against Undisclosed Targets Expressed in Solid Tumors
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24 Target Properties•Tumor Expression:Major solid tumors including colorectal, ovarian, breast, and NSCLC•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 programTarget Properties•Tumor Expression:Major solid tumors including colorectal, ovarian, breast, and NSCLC•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 programIM-1617’s Target is Expressed in Solid Tumor Indications with Significant Unmet NeedIM-1617’s Target is Expressed in Solid Tumor Indications with Significant Unmet NeedNovel ADC #1: Pursuing a Novel ADC Target with Multi-Indication Solid Tumor Potential 0255075100 NegativeLowModerateHigh
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25 In Vivo Efficacy StudiesIn Vivo Efficacy StudiesIM-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 tumorsTolerability•Initial NHP study found a HNSTD of 40 mg/kg, indicating robust therapeutic windowIM-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 tumorsTolerability•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-Enabling Work Initiated in Q4 2024Preclinical Efficacy: Regressions achieved after a single clinically relevant dose in tumor models derived from melanoma, esophageal, CRC, NSCLC, and other carcinomasPreclinical Efficacy: Regressions achieved after a single clinically relevant dose in tumor models derived from melanoma, esophageal, CRC, NSCLC, and other carcinomas0 510 15 20 25 30 350100020003000Esophageal (KYSE30)Days Post Treatment Start VehicleIsotype ADC, 5 mg/kgIM-1617, 2.5 mg/kgIM-1617, 5 mg/kg Mean Tumor Volume (mm3)
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26 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 programIdentifying 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 programIM-1340’s Target is Expressed in Neuroendocrine Tumors, Lung, and ProstateIM-1340’s Target is Expressed in Neuroendocrine Tumors, Lung, and ProstateNovel ADC #2: 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 0255075100IHC Score(Percent of Total)NegativeLowModerateHigh
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27 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 actionTolerability•Initial NHP study found a HNSTD of 40 mg/kg, indicating robust therapeutic windowIM-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 actionTolerability•Initial NHP study found a HNSTD of 40 mg/kg, indicating robust therapeutic windowPreclinical Efficacy: Regression achieved after a single dose of 1 mg/kg in in vivo tumor models including pancreatic, prostate, SCLC, and NSCLCPreclinical Efficacy: Regression achieved after a single dose of 1 mg/kg in in vivo tumor models including pancreatic, prostate, SCLC, and NSCLCIn Vivo Preclinical EfficacyIn Vivo Preclinical EfficacyIM-1340 is a Potential First-in-Class ADC that Shows Robust Efficacy in a Range of Models IND-Enabling Work Initiated in Q4 20240 510 15 20 25 30 350500100015002000SCLC (NCI-H1105)Days Post Treatment StartMean Tumor Volume (mm3)VehicleIsotype ADC, 5 mg/kgIM-1340, 1 mg/kgIM-1340, 2.5 mg/kgIM-1340, 5 mg/kg0 510 15 20 25 3005001000150020002500NSCLC (CALU6)Mean Tumor Volume (mm3)VehicleIsotype ADC, 5 mg/kgIM-1340, 2.5 mg/kgIM-1340, 5 mg/kg
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28 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 dateRevisiting 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 dateNovel ADC #3: ADC Optimization Driven by Understanding Biology of a Known TargetIn Vivo Preclinical EfficacyIn Vivo Preclinical Efficacy0 510 15 200500100015002000Solid Tumor IndicationMean Tumor Volume (mm3)IM-1335, 5 mg/kgIM-1335, 2.5 mg/kgIsotype ADC, 5 mg/kgVehicleIND-Enabling Work Initiated in Q4 2024
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29 In Vivo Preclinical Efficacy for Three Additional CandidatesIn Vivo Preclinical Efficacy for Three Additional CandidatesAdditional Discovery-Stage Candidates Demonstrate Solid Tumor Activity•Immunome has generated in vivodata for over 15 distinct targets, with six currently undergoing lead optimization•Tumor regressions achieved at doses of 5 mg/kg or lower in major indications including•Breast Cancer•Colorectal cancer•Lung Cancer•Ovarian Cancer•Additional candidates expected to be advanced to development as appropriate•Potential opportunities for partnerships and non-dilutive financing•Immunome has generated in vivodata for over 15 distinct targets, with six currently undergoing lead optimization•Tumor regressions achieved at doses of 5 mg/kg or lower in major indications including•Breast Cancer•Colorectal cancer•Lung Cancer•Ovarian Cancer•Additional candidates expected to be advanced to development as appropriate•Potential opportunities for partnerships and non-dilutive financing Mean Tumor Volume (mm3) Mean Tumor Volume (mm3) Mean Tumor Volume (mm3)
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30 IM-3050FAP-Targeted Radioligand Therapy
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31 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)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 typesFAP imaging shows high expression across 15 distinct tumor typesFAP 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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32 Immunome has systematically selected a ligand, linker, albumin binding domain, and payload to optimize:•Binding and specificity•Stability•Pharmacokinetics•Tumor absorbed dose•Efficacy•TolerabilityImmunome 177Lu-FAP Candidates are Rationally Designed and Systematically ScreenedImmunome Approach Example Structure:FAP binding and specificity optimizedProven structure used by Pluvicto and Lutathera to deliver Lu-177 isotopeProven structure used by Pluvicto and Lutathera to deliver Lu-177 isotopeAlbumin binding domain selected to maximize tumor retentionOptimized linker reduces non-specific uptakeOptimized linker reduces non-specific uptakeOptimized ligand potentially leads to:•Increased tumor uptake and retention•Superior efficacy•Stability and ease of manufactureIncorporating albumin binder potentially extends circulating half-life and increases tumor residence time, leading to superior tumor absorbed dose in vivoFAP LigandLinkerChelatorAlbumin Binder
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33 IM-3050 is a 177Lu-FAP Candidate with Best-in-Class PotentialTumor Regression in U87MG ModelTumor Regression in U87MG ModelNo Weight Loss ObservedNo Weight Loss ObservedPotential Best-in-Class CharacteristicsSub-nanomolar affinityHigh specificityRadiostabilitySuperior tumor retention and tumor absorbed dose in vivoPreclinical activity and tolerabilityPotential Best-in-Class CharacteristicsSub-nanomolar affinityHigh specificityRadiostabilitySuperior tumor retention and tumor absorbed dose in vivoPreclinical activity and tolerabilityDEVELOPMENT STATUS:IND filing anticipated 1Q25In Vivo Radiotherapy StudiesGLP/GMP ManufacturingPrepare IND package✓Clinical Formulation Development✓ In vivo data show single dose antitumor activity and tolerability Relative body weight(% of pretreatment) Tumor Volume(% of pretreatment) ✓✓
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34 •Fully enrolled Phase 3 trial for varegacestat (formerly AL102)•IND-stage programs with best-in-class or first-in-class potential:•IM-1021: ROR1 ADC•IM-3050: FAP RLT•Three novel solid-tumor targeted ADCs in preclinical development: IM-1617, IM-1335, and IM-1340•Differentiated technology to (re)invent ADCs•Large repertoire of novel, ADC-optimized antibodies•Efficient, productive business development efforts•Cash expected to extend into 2026 Building the Foundation of the Next Transformative ADC Company