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© Immatics. Not for further reproduction or distribution. Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. IMA203 PRAME Cell Therapy in Advanced Melanoma - Phase 1b Dose Expansion Clinical Data Update May 31, 2025 Data cut-off April 7, 2025
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Background and Key Takeaways • Frequent recurrence and limited long-term survival with unresectable or metastatic melanoma highlight the critical need for new treatments that deliver deeper, more durable responses1-3 • IMA203 is a PRAME-directed TCR T-cell therapy engineered to recognize an intracellular PRAME-derived peptide presented by HLA-A*02:01 on the cell surface and initiate a potent and specific anti-tumor response4 • IMA203 exhibited favorable tolerability, with anticipated lymphodepletion-associated cytopenias, mostly mild-to-moderate CRS, infrequent ICANS, and no IMA203-related grade 5 events • One-time infusion of IMA203 has promising clinical activity in heavily pretreated patients with metastatic melanoma (n=33): – cORR: 56% (18/32) – mDOR: 12.1 mo (range: 1.8+, 32.6+) at mFU of 13.4 mo – mPFS: 6.1 mo (range: 1.4, 34.0+) at mFU of 14.4 mo – mOS: 15.9 mo (range: 2.4, 34.2+) at mFU of 14.4 mo • Encouraging activity was seen in both cutaneous melanoma (cORR 50%) and uveal melanoma (cORR 67%) 1 Mooradian MJ, et al. Oncology (Williston Park). 2019;33:141-148. 2 Hamid O, et al. Ann Oncol. 2019;30:582-588. 3 Goldinger SM, et al. Eur J Cancer. 2022;162:22-33. 4 Wermke M, et al. Nat Med. 2025; doi: 10.1038/s41591-025-03650-6 [online ahead of print]. cORR, confirmed objective response rate; CRS, cytokine release syndrome; ICANS, Immune effector cell-associated neurotoxicity syndrome; mDOR, median duration of response; mFU, median follow-up; mPFS, median progression-free survival; mOS, median overall survival 2Data cut-off Apr 7, 2025 ASCO 2025
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PRAME Is Expressed in More Than 50 Cancers 3 ≥95 % ≥10 % PRAME prevalence in selected indications Indication % PRAME+ patients1 Cutaneous Melanoma 95% Uterine Carcinoma 95% Uterine Carcinosarcoma 95% Synovial Sarcoma 95% Uveal Melanoma 90% Mucosal Melanoma 90% Ovarian Carcinoma Subtypes 85% Squamous Cell NSCLC2 70% Triple-negative Breast Carcinoma 65% Small Cell Lung Cancer 45% Esophageal Carcinoma Subtype 45% Kidney Carcinoma Subtype 40% Cholangiocarcinoma 35% HER2-Enriched Breast Carcinoma 30% Adenocarcinoma NSCLC2 25% Head & Neck Squamous Cell Carcinoma 25% Hepatocellular Carcinoma 20% Bladder Carcinoma 20% 3 Indication Cutaneous Melanoma Endometrioid Endometrial Carcinoma Uterine Carcinosarcoma Synovial Sarcoma Acral Melanoma Uveal Melanoma Mucosal Melanoma Endometrial Clear Cell Carcinoma Endometrial Serous Carcinoma Ovarian Serous Cystadenocarcinoma Ovarian Clear Cell Carcinoma Ovarian Endometrioid Carcinoma Head and Neck Salivary Duct Carcinoma Adenoid Cystic Carcinoma Neuroblastoma Malignant Rhabdoid Tumor Wilms Tumor (Nephroblastoma) Squamous Cell NSCLC Triple Negative Breast Carcinoma (TNBC) Cervical Adenosquamous Cell Carcinoma Large Cell Neuroendocrine Lung Carcinoma (LCNEC) Basal Cell Carcinoma Mucoepidermoid Carcinoma Large Cell Lung Carcinoma (LCLC) Spindle Cell Melanoma Testicular Germ Cell Tumor (Seminoma and Non-Seminoma) Myxoid Liposarcoma Angiosarcoma Small Cell Lung Cancer (SCLC) Esophageal Small Cell Carcinoma Cutaneous Squamous Cell Carcinoma Thymoma Merkel Cell Carcinoma Endometrial Sarcoma Esophageal Squamous Carcinoma Esophageal Adenosquamous Carcinoma Kidney Renal Papillary Cell Carcinoma Malignant Peripheral Nerve Sheath Tumor (MPNST) Cholangiocarcinoma Cervical Adenocarcinoma Head and Neck Salivary Gland Carcinoma Osteosarcoma HER2-Enriched Breast Carcinoma Embryonal Rhabdomyosarcoma Adenosquamous NSCLC Diffuse Large B-cell Lymphoma (DLBCL) Sarcomatoid Carcinoma of the Lung Adenocarcinoma NSCLC Head and Neck Squamous Cell Carcinoma (HNSCC) Alveolar Rhabdomyosarcoma Ovarian Mucinous Carcinoma Adrenocortical Carcinoma Kidney Renal Clear Cell Carcinoma Hepatocellular Carcinoma Bladder Urothelial Carcinoma Cervical Squamous Cell Carcinoma Non-Squamous Anal Carcinoma Pancreatic Neuroendocrine Adenocarcinoma Prostate Neuroendocrine Adenocarcinoma Liposarcoma Undifferentiated Pleomorphic Sarcoma Acute Myeloid Leukemia (AML) Ewing Sarcoma Ovarian Leiomyosarcoma Breast Carcinoma, Luminal A Breast Carcinoma, Luminal B Squamous Anal Carcinoma Stomach Adenocarcinoma Esophageal Adenocarcinoma Fibrosarcoma Anaplastic Thyroid Carcinoma (…) 1 Data on file: PRAME target prevalence is based on a proprietary mass spec-guided expression threshold applied to RNAseq and/or IHC data (approximate values, values between 95-100% shown as 95%); 2 NSCLC: Non-small cell lung cancer; Precision targeting of PRAME
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Phase 1 Study Design: IMA203 in Advanced Solid Tumors Expressing PRAME Key Objectives Primary: • Tolerability • Determination of RP2D (Phase 1a) Secondary: • IMA203 T cell engraftment, persistence • Efficacy Key Eligibility Criteria • Confirmed advanced and/or metastatic solid tumor • Patients ≥ 18 years of age • ECOG performance status 0-1 • HLA-A*02:01 and PRAME positive • Patients having received, or not been eligible for all available indicated SOC treatment • Adequate organ function • No active brain metastasis a Outpatient administration at investigator’s discretion. BID, twice daily; IU, international unit; ECOG, Eastern Cooperative Oncology Group; FU, follow-up; RP2D, recommended phase 2 dose at 1-10x109 TCR T cells; QC, quality control; SC, subcutaneous; SOC, standard of care. 1 Gragert et al. 2013 and census numbers. HLA-A*02:01 prevalence in Immatics’ clinical trials: US 65% and Germany 55% as of March 2025. Manufacturing success rate as of Apr 7, 2025 4 SCREENING/MANUFACTURING Leukapheresis IMA203 One-time infusion Lymphodepletion Fludarabine 30mg/m2 Cyclophosphamide 500mg/m2 Days -6 to -3 Low Dose IL-2a 1m IU SC Days 1-5; 1m IU SC BID Days 6-10 PRAME Testing Biopsy or archived tissue Inclusion of PRAME- positive patients TREATMENT / OBSERVATION FU HLA-A*02:01 Testing Blood Inclusion of HLA-A*02:01- positive patients Prevalence1: US: 41% EU: 48% Manufacturing of IMA203 ~2 weeks turnaround time (applying CD8/CD4 T cell selection, incl. QC release testing) 95% success rate to reach RP2D Patient Journey Data cut-off Apr 7, 2025 ASCO 2025
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IMA203 Phase 1 Study: Patient Disposition 5 1 Melanoma efficacy population excludes 1 patient with uveal melanoma with ongoing unconfirmed PR from cORR; 2 Mucosal melanoma n=2, melanoma of unknown primary n=1; RP2D: 1-10x109 TCR T cells; DL4: 0.2-1.2x109 TCR T cells/m2 BSA; DL: dose level. Total Safety Population (N=74) Melanoma Efficacy Population1 (n=33) n=13 non-melanoma n=3 other melanoma2 n=14 cutaneous melanoma n=16 uveal melanoma n=27 Phase 1a Dose Escalation (DL1-4) n=1 in Phase 1a started lymphodepletion but did not receive IMA203 n=46 Phase 1b Dose Expansion (RP2D) RP2D defined at 1-10x109 TCR T cells Data cut-off Apr 7, 2025 ASCO 2025
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IMA203 Phase 1 Study: Baseline Characteristics & Treatment Experience CM, cutaneous melanoma; ECOG, Eastern Cooperative Oncology Group; ICI, immune checkpoint inhibitor; LDH, lactate dehydrogenase; MM, mucosal melanoma; TCR, T-cell receptor; UkM, melanoma of unknown primary; UM, uveal melanoma. 6 Baseline Characteristics Total Safety Population N=74 Cutaneous Melanoma n=14 Uveal Melanoma n=16 All Melanoma n=33 Age, median (range) 54 (18, 79) 54.5 (31, 79) 62 (32, 74) 57 (31, 79) Female, % 52.7 21.4 62.5 48.5 Baseline ECOG status 1, % 51.4 35.7 43.8 39.4 Prior lines of systemic treatment, median (range) 3 (0, 10) 2.5 (1, 5) 2 (0, 6) 2 (0, 6) Prior ICI treatment, median (range) ≥1 line of PD1/CTLA4, % Prior tebentafusp, % --- --- --- 2 (1, 3) 100/64.3 --- 1 (0, 4) 62.5/43.8 62.5 1 (0, 4) 81.8/57.6 --- Elevated LDH at baseline, % 63.5 64.3 56.3 57.6 Median target lesion sum of diameter, mm (range) 116.1 (15.0, 309.8) 120.5 (15.0, 309.8) 101.6 (30.8, 210.0) 104.0 (15.0, 309.8) Patients with liver metastasis, % 62.2 64.3 93.8 78.8 Patients with brain metastasis, % 12.2 0.0 0.0 3.0 Metastatic staging, % (CM, MM, UkM only) IIIb/IIIc/IVM1a IVM1b/c/d --- --- 0.0 100.0 --- --- 0.0 100.0 Metastatic staging, % (UM only) IVM1a IVM1b/c/d --- --- --- --- 18.8 81.3 --- --- Treatment Experience Total Safety Population Cutaneous Melanoma Uveal Melanoma All Melanoma Infused TCR T cell dose (x109), median (range) 2.34 (0.078, 10.20) 4.58 (1.30, 10.20) 3.94 (1.62, 8.43) 4.04 (1.30, 10.20) Melanoma Efficacy Population Heavily Pretreated Patient Population Data cut-off Apr 7, 2025 ASCO 2025
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IMA203 Safety: Adverse Events Occurring in ≥20% of Patients N=74 Patients Across All Dose Levels in Phase 1a/b (Total Safety Population) 7 Patients are counted only once per adverse event and severity classification. 1 Two patients with disease progression after first IMA203 infusion received exploratory second IMA203 infusion. They had these ≥ Grade 3 TEAEs only after second infusion, which are included in the table: First patient: CRS, diarrhea; Second patient: neutropenia, thrombocytopenia. CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; HLH, hemophagocytic lymphohistiocytosis; TEAE, treatment-emergent adverse event. Preferred terms, n (%) N=74 Any grade Grade ≥3 Blood and lymphatic system disorders 73 (98.6) 73 (98.6) Neutropenia1 68 (91.9) 67 (90.5) Anaemia 57 (77.0) 38 (51.4) Thrombocytopenia1 50 (67.6) 27 (36.5) Leukopenia 39 (52.7) 38 (51.4) Lymphopenia 39 (52.7) 39 (52.7) Gastrointestinal disorders 65 (87.8) 2 (2.7) Nausea 45 (60.8) 0 (0.0) Diarrhoea1 28 (37.8) 1 (1.4) Vomiting 25 (33.8) 1 (1.4) Constipation 23 (31.1) 0 (0.0) General disorders and administration site conditions 49 (66.2) 2 (2.7) Fatigue 29 (39.2) 1 (1.4) Pyrexia 22 (29.7) 1 (1.4) Edema peripheral 17 (23.0) 0 (0.0) Investigations 35 (47.3) 10 (13.5) Aspartate aminotransferase increased 29 (39.2) 5 (6.8) Alanine aminotransferase increased 28 (37.8) 7 (9.5) Blood creatinine increased 15 (20.3) 2 (2.7) Skin and subcutaneous tissue disorders 35 (47.3) 6 (8.1) Rash 18 (24.3) 0 (0.0) Rash maculo-popular 18 (24.3) 6 (8.1) Metabolism and nutrition disorders 33 (44.6) 6 (8.1) Hyponatraemia 22 (29.7) 3 (4.1) Hypokalaemia 21 (28.4) 3 (4.1) • Tolerability consistent with previous report • Most frequent TEAEs were anticipated cytopenias associated with lymphodepletion • Expected and manageable CRS, mostly Grade 1/2, consistent with mechanism of action • Infrequent, manageable, and mostly mild ICANS • No IMA203-related Grade 5 events • Tolerability in the melanoma subset generally consistent with the full IMA203 tolerability profile Adverse events of special interest TEAEs in ≥20% of patients N=74 CRS, any grade, n (%) 70 (94.6) Grade 1 27 (36.5) Grade 2 35 (47.3) Grade 31 8 (10.8) Grade 4 0 (0.0) Grade 5 0 (0.0) ICANS, any grade, n (%) 10 (13.5) Grade 1 4 (5.4) Grade 2 3 (4.1) Grade 3 3 (4.1) Grade 4 0 (0.0) Grade 5 0 (0.0) HLH, any grade, n (%) 2 (2.7) Grade 1 0 (0.0) Grade 2 1 (1.4) Grade 3 1 (1.4) Grade 4 0 (0.0) Grade 5 0 (0.0) Data cut-off Apr 7, 2025 ASCO 2025
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IMA203: Best Overall Response in Melanoma Efficacy Population 56% Confirmed Objective Responses in Heavily Pretreated Patients with Metastatic Melanoma 8 *Maximum change of target lesions and RECIST1.1 response at different timepoints. 1 Patient out of study due to PD (external assessment); 2 Patient out of study at data-cut (withdrew consent); 3 Includes melanoma (other) n=3: mucosal melanoma n=2, melanoma of unknown primary n=1; Melanoma efficacy population excludes 1 uveal melanoma patient with ongoing unconfirmed PR from cORR; (c)ORR: (confirmed) objective response rate; DCR: disease control rate at week 6; BL: baseline; (c)CR: (confirmed) complete response; (c)PR: (confirmed) partial response; SD: stable disease; PD: progressive disease. n=14 n=16 n=3 n=33 cORR 50% (7/14) 67% (10/15) 1/3 56% (18/32) ORR 57% (8/14) 69% (11/16) 2/3 64 % (21/33) DCR 93% (13/14) 88% (14/16) 3/3 91% (30/33) Cutaneous Melanoma Uveal Melanoma Melanoma (other) All Melanoma3 Data cut-off Apr 7, 2025 ASCO 2025
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IMA203: Duration of Response in Melanoma Efficacy Population Prolonged Ongoing Responses up to 2.5+ Years after Treatment 9 1 Patient out of study due to PD (external assessment); 2 Patient out of study at data-cut (withdrew consent); 3 Includes melanoma (other) n=3: mucosal melanoma n=2, melanoma of unknown origin n=1; mDOR, median duration of response; mFU, median follow-up; NR, not reached; SD: stable disease; PD: progressive disease; BL: baseline; (c)PR: (confirmed) partial response; (c)CR: (confirmed) complete response Data cut-off Apr 7, 2025 ASCO 2025 Scans at approximately week 6, month 3 and then every 3 months Ongoing Cutaneous Melanoma n=14 Uveal Melanoma n=16 All Melanoma3 n=33 mDOR [mo], (range) mFU [mo] NR (4.2, 32.6+) 16.7 11.0 (1.8+, 31.6) 13.4 12.1 (1.8+, 32.6+) 13.4
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IMA203: Survival Outcomes in Melanoma Efficacy Population 10 Median Progression Free Survival Median Overall Survival Data cut-off Apr 7, 2025 ASCO 2025 Cutaneous Melanoma n=14 Uveal Melanoma n=16 All Melanoma 1 n=33 mPFS [mo] (range) mFU [mo] 6.0 (1.4 , 34.0+) 14.4 8.5 (1.4, 32.9) 8.7 6.1 (1.4, 34.0+) 14.4 Cutaneous Melanoma n=14 Uveal Melanoma n=16 All Melanoma 1 n=33 mOS [mo] (range) mFU [mo] 13.9 (2.4, 34.0+) 14.4 16.2 (3.2+, 34.2+) 14.5 15.9 (2.4, 34.2+) 14.4 12-month OS rate: 61%6-month PFS rate: 53% 12-month PFS rate: 27% 1 Includes melanoma (other) n=3: mucosal melanoma n=2, melanoma of unknown origin n=1; PFS and OS censored at data-cut; PFS and OS rate shown as % of evaluable patients at indicated timepoint. mFU, median follow-up; mOS, median overall survival; mPFS, median progression-free survival.
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IMA203: Enhanced mPFS of >1 Year in Melanoma Patients with Deep Responses 11Data cut-off Apr 07, 2025 • 42% (14/33) patients in dose expansion have a deep response (≥50% tumor reduction) • This subgroup of patients has highly medically meaningful mPFS of more than 1 year • Patients with <50% tumor reduction (including tumor size increase) still observe a more than 2x longer mPFS as compared to patients treated in dose escalation with suboptimal doses n mPFS mFU Dose Escalation IMA203 11 2.6 ND Dose Expansion IMA203 <50% tumor size reduction (inlcuding tumor size increase) 19 5.8 8.7 Dose Expansion IMA203 ≥50% tumor size reduction 14 12.9 19.5 Log-rank: 0.019 ND, not defined; mFU, median follow-up; mPFS, median progression-free survival.
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n 41 14 23 11 4 17 Median shrinkage -48.9% -44.9% -54.2% -62.6% -22.1% -46.2% IMA203: Responses of Metastases Throughout the Body in Melanoma Efficacy Population Shrinkage in Difficult-to-Treat Target Lesions Including Liver 12Other: brain, kidney, pelvis, pericardium, pleura, bone, adrenal, retroperitoneum, rectum, soft tissue, gluteal, dorsal Data cut-off Apr 7, 2025 ASCO 2025
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IMA203 PRAME Cell Therapy: Conclusions Extended Phase 1 Data Continues to Show Strong Anti-tumor Activity and Durability • IMA203 PRAME-directed TCR T-cell therapy exhibited favorable tolerability, with anticipated lymphodepletion- associated cytopenias, mostly mild-to-moderate CRS, infrequent ICANS, and no IMA203-related grade 5 events • One-time infusion of IMA203 has promising clinical activity in heavily pretreated patients with metastatic melanoma (n=33): • cORR: 56% (18/32) • mDOR: 12.1 mo (range: 1.8+, 32.6+) at mFU of 13.4 mo • mPFS: 6.1 mo (range: 1.4, 34.0+) at mFU of 14.4 mo • mOS: 15.9 mo (range: 2.4, 34.2+) at mFU of 14.4 mo • Encouraging activity was observed in both cutaneous melanoma (cORR 50%) and uveal melanoma (cORR 67%) • Given its promising Phase 1 profile with high PRAME prevalence in melanoma, a registration-directed Phase 3 trial (SUPRAME; NCT06743126) is underway in previously treated advanced or metastatic cutaneous melanoma cORR, confirmed objective response rate; CRS, cytokine release syndrome; ICANS, Immune effector cell-associated neurotoxicity syndrome; mDOR, median duration of response; mFU, median follow-up; mPFS, median progression-free survival; mOS, median overall survival. 13Data cut-off Apr 7, 2025 ASCO 2025
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SUPRAME: A Randomized Phase 3 Trial of IMA203 PRAME-directed TCR T-cell Therapy vs Investigator’s Choice in Unresectable or Metastatic Melanoma post ICI Actively Enrolling, >50 Sites Planned across North America and Europe 14 IMA203 n=180 Investigator’s choice n=180 Primary Endpoint • PFS Key Secondary Endpoint • Overall survival Randomization 1:1 Patient Population: Unresectable or metastatic melanoma post ICI N=360 nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (US), chemotherapy 1 A pre-specified interim data analysis will be triggered upon the occurrence of a defined number of events for PFS (progressive disease or death) anticipated to occur after approximately 200 patients are enrolled; 2 Triggered upon the occurrence of a defined number of events for PFS (progressive disease or death); ICI: immune checkpoint inhibitor; PFS: progression-free survival; ORR: objective response rate; TESAEs: treatment-emergent serious adverse events; AE: adverse event; EORTC: European Organization for Research and Treatment of Cancer; QLQ-C30: Core Quality of Life questionnaire; EQ-5D-5L: European Quality of Life 5 Dimensions 5 Level Version Secondary Endpoints • Efficacy: ORR • Safety: TESAEs, AEs of special • interest • Quality of life: EORTC QLQ-C30 and EQ-5D-5L Expected timelines of the SUPRAME trial December 2024 SUPRAME Phase 3 trial start Q1 2026 Interim analysis1 Q4 2026 Final analysis2 Q1 2027 BLA submission Q3 2027 Launch
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15 IMA203 Phase 1 Study Sponsor: Immatics University Hospital Dresden University Hospital Bonn University Hospital Würzburg University Hospital Hamburg Germany Charité Berlin University Hospital Heidelberg University Medicine Mainz Columbia University University of Pittsburgh MD Anderson Cancer Center United States University of Miami Health System Fox Chase Cancer Center Thank You to the Patients, their Families and the Participating Clinical Trial Sites Data cut-off Apr 7, 2025 ASCO 2025
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Appendix 16
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IMA203 Phase 1 Study: Baseline Characteristics & Treatment Experience Including Melanoma Dose Escalation Population 17Data cut-off Apr 7, 2025 Treatment Experience Total Safety Population Melanoma Dose Escalation Population Melanoma Efficacy Population Infused TCR T cell dose (x109), median (range) 2.34 (0.078, 10.20) 0.586 (0.099, 2.09) 4.04 (1.30, 10.20) Baseline Characteristics Total Safety Population N=74 Melanoma Dose Escalation Population n=11 Melanoma Efficacy Population n=33 Age, median (range) 54 (18, 79) 51 (18, 72) 57 (31, 79) Female, % 52.7 45.5 48.5 Baseline ECOG status 1, % 51.4 63.6 39.4 Prior lines of systemic treatment, median (range) 3 (0, 10) 4 (2, 7) 2 (0, 6) Prior ICI treatment, median (range) ≥1 line of ICI treatment, % (n/N) Prior tebentafusp, % (n/N) (UM only) --- --- --- 2 (1, 4) 100% (11/11) 50% (1/2) 1 (0, 4) 81.8 (27/33) 62.5 (10/16) Elevated LDH at baseline, % 63.5 81.8 57.6 Median target lesion sum of diameter, mm (range) 116.1 (15.0, 309.8) 117.5 (37.0, 211.0) 104.0 (15.0, 309.8) Patients with liver metastasis, % 62.2 54.5 78.8 Patients with brain metastasis, % 12.2 27.3 3.0 Metastatic staging, % (CM, MM, UkM only) IIIb/IIIc/IVM1a IVM1b/c/d 3.8 (1/26) 96.2 (25/26) 11.1 (1/9) 88.9 (8/9) 0.0 (0/17) 100.0 (17/17) Metastatic staging, % (UM only) IVM1a IVM1b/c/d 15.8 (3/19) 84.2 (16/19) 0.0 (0/2) 100 (2/2) 18.8 (3/16) 81.3 (13/16) ICI: immune checkpoint inhibitor; LDH: lactate dehydrogenase; CM: cutaneous melanoma; MM: mucosal melanoma; UkM: melanoma of unknown primary; UM: uveal melanoma
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IMA203: Significant Shift in PFS and OS Between Dose Escalation & Dose Expansion PFS of 6 Months and OS of 16 Months in Melanoma Efficacy Population 18 Progression Free Survival Data cut-off Apr 07, 2025 Overall Survival N mPFS Dose Escalation 11 2.6 months Dose Expansion 33 6.1 months N mOS Dose Escalation 11 6.3 months Dose Expansion 33 15.9 months • Significant shift in mPFS and mOS between melanoma patients treated during the dose escalation and dose expansion • mPFS in dose escalation is comparable to reported data in 2L+ cut. melanoma population* • mOS in dose escalation is shorter than reported mOS for 2L+ cut. melanoma population* • All patients in the dose escalation group deceased and 17/30 evaluable patients are alive in dose expansion# Log-rank test: p <0.0001 Log-rank test: p <0.0001 Overall survival (OS) and progression-free survival (PFS) censored at data-cut; * These data are derived from different clinical trials at different points in time with differences in trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted # 3 patients out of study at data-cut (withdrew consent)
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Tolerability Profile of IMA203 Across All Dose Levels in Phase 1a/b All ≥ Grade 3 Adverse Events (N=74) 19 Adverse event (System organ class, Preferred term) ≥ Grade 3 No. % Patients with any adverse event 74 100.0 Adverse Events of Special Interest 10 13.5 Cytokine release syndrome1 8 10.8 ICANS2 3 4.1 Haemophagocytic lymphohistiocytosis 1 1.4 Blood and lymphatic system disorders 73 98.6 Neutropenia1 67 90.5 Lymphopenia 39 52.7 Anaemia 38 51.4 Leukopenia 38 51.4 Thrombocytopenia1 27 36.5 Febrile neutropenia 2 2.7 Cytopenia 1 1.4 Leukocytosis 1 1.4 Infections and infestations 12 16.2 Urinary tract infection 2 2.7 Appendicitis 1 1.4 COVID-19 1 1.4 Cytomegalovirus infection reactivation 1 1.4 Enterococcal infection 1 1.4 Fournier's gangrene 1 1.4 Human herpesvirus 6 encephalitis 1 1.4 Infection 1 1.4 Orchitis 1 1.4 Pneumonia 1 1.4 Sepsis3,4 1 1.4 Septic shock3 1 1.4 Investigations 11 14.9 Alanine aminotransferase increased 7 9.5 Aspartate aminotransferase increased 5 6.8 Blood creatinine increased 2 2.7 Blood alkaline phosphatase increased 1 1.4 Blood bilirubin increased 1 1.4 Blood fibrinogen decreased 1 1.4 Lymphocyte count increased 1 1.4 Respiratory, thoracic and mediastinal disorders 10 13.5 Hypoxia 4 5.4 Pleural effusion 2 2.7 Bronchial obstruction 1 1.4 Dyspnoea 1 1.4 Epistaxis 1 1.4 Laryngeal inflammation 1 1.4 Respiratory failure 1 1.4 Adverse event (System organ class, Preferred term) ≥ Grade 3 No. % table continued… Metabolism and nutrition disorders 7 9.5 Hypokalaemia1 3 4.1 Hyponatraemia 3 4.1 Hypophosphataemia 2 2.7 Dehydration 1 1.4 Failure to thrive 1 1.4 Skin and subcutaneous tissue disorders 7 9.5 Rash maculo-papular 6 8.1 Eczema 1 1.4 Vascular disorders 7 9.5 Hypertension 6 8.1 Hypotension 1 1.4 Gastrointestinal disorders 5 6.8 Abdominal pain1 3 4.1 Diarrhoea1 1 1.4 Ileus 1 1.4 Vomiting 1 1.4 Renal and urinary disorders 5 6.8 Acute kidney injury 4 5.4 Proteinuria1 1 1.4 General disorders and administration site conditions 4 5.4 Fatigue 1 1.4 General physical health deterioration3 1 1.4 Pyrexia 1 1.4 Swelling face 1 1.4 Cardiac disorders 3 4.1 Atrial fibrillation5 3 4.3 Eye disorders 2 2.7 Periorbital oedema 1 1.4 Ulcerative keratitis 1 1.4 Injury, poisoning and procedural complications 2 2.7 Humerus fracture1 1 1.4 Infusion related reaction 1 1.4 Musculoskeletal and connective tissue disorders 2 2.7 Back pain 1 1.4 Muscle spasms1 1 1.4 Adverse event (System organ class, Preferred term) ≥ Grade 3 No. % table continued… Nervous system disorders 2 2.7 Headache 1 1.4 Posterior reversible encephalopathy syndrome 1 1.4 Endocrine disorders 1 1.4 Inappropriate antidiuretic hormone secretion 1 1.4 Hepatobiliary disorders 1 1.4 Cholangitis 1 1.4 Reproductive system and breast disorders 1 1.4 Vaginal haemorrhage 1 1.4 All treatment-emergent adverse events (TEAEs) with ≥ Grade 3 regardless of relatedness to study treatment. Adverse events were coded using the Medical Dictionary for Regulatory Activities. Grades were determined according to National Cancer Institute Common Terminology Criteria of Adverse Events, version 5.0. Grades for Cytokine release syndrome and ICANS were determined according to CARTOX criteria (Neelapu et al., 2019). Patients are counted only once per adverse event and severity classification. Based on interim data extracted from open clinical database (07-Apr-2025); 1 Two patients with disease progression after first IMA203 infusion received exploratory second IMA203 infusion. They had these ≥ Grade 3 TEAEs only after second infusion, which are included in the table: First patient: Abdominal pain, Cytokine release syndrome, Diarrhoea, Hypokalaemia, Proteinuria; Second patient: Humerus fracture, Muscle spasms, Neutropenia, Thrombocytopenia; 2 ICANS: Immune effector cell-associated neurotoxicity syndrome; 3 Fatal Adverse events were not considered related to any study drug; 4 Patient died from sepsis of unknown origin and did not receive IMA203 TCR-T cells; 5 DLT: Dose limiting toxicity in phase 1a at DL2 reported on March 17, 2021. Data cut-off Apr 7, 2025
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CRS Events and Interventions After IMA203 Infusion in Melanoma Efficacy Population Manageable and Consistent with Mechanism of Action 20 • Median day of onset (range): 1 (0, 3) • Median duration, days (range): 9 (2, 27) • Most CRS resolved by day 14 • No long-term CRS CRS Interventions Data cut-off Apr 7, 2025 n=33 Interventions, n (%) 24 (72.7) Tocilizumab 23 (69.7) Steroids 11 (33.3) CRS Dynamics CRS, cytokine release syndrome Grade 3 1 2
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Melanoma Efficacy Population (n=33) Patients with Melanoma Treated with IMA203 in Phase 1b Dose Expansion Patient ID Indication No of prior treatment lines Prior treatments Total infused dose TCR-T cells1 [x109] BOR BOR (Max % change of target lesions) Comment Reason for Progression A-DL4-03 Cut. Melanoma 5 Dabrafenib + TrametinibPembrolizumabDabrafenib + Trametinib + Vemurafenib + CobimetinibTebentafuspEncorafenib + Binimetinib 1.30 cPR -78.3 Ongoing response at 34.0 months PFS A-DL5-13 Cut. Melanoma 3 Nivolumab PembrolizumabIpilimumab + Nivolumab 9.80 cPR -65.6 Ongoing response at 19.5 months PFS A-DL5-26 Uveal Melanoma 2 MelphalanTebentafusp 8.14 cPR -76.6 Ongoing response at 14.8 months PFS A-DL5-27 Cut. Melanoma 1 Relatlimab + Nivolumab 10.20 cCR -73.3 Ongoing response at 14.4 months PFS A-DL5-31 Cut. Melanoma 3 Ipilimumab + NivolumabZimberelimab + DomvanalimabEncorafenib + Binimetinib 3.68 SD -18.8 Ongoing disease stabilization at 11.7 months PFS A-DL5-32 Uveal Melanoma 6 Ipilimumab + NivolumabTebentafuspMelphalanIpilimumab + NivolumabDYP-688Ipilimumab + Nivolumab 3.18 cPR -39.5 Ongoing response at 8.7 months PFS A-DL4-09# Uveal Melanoma 3 Ipilimumab + NivolumabDarovasertibTebentafusp 1.62 PR -43.8 Initial disease stabilization transitioned into unconfirmed response ongoing at 7.8 months PFS A-DL4-10* Uveal Melanoma 1 Tebentafusp 1.62 cPR -41.7 Ongoing response at 5.1 months PFS A-DL5-34* Uveal Melanoma 1 Tebentafusp 3.68 cPR -50.0 Ongoing response at 4.9 months PFS A-DL5-36* Uveal Melanoma 1 Brenetafusp 7.93 cPR -60.4 Ongoing response at 3.2 months PFS A-DL5-01 Uveal Melanoma 1 ARRY614 + Nivolumab 4.16 cPR -83.9 Response until 32.9 months PFS New lesions A-DL5-03 Cut. Melanoma 3 InterferonPembrolizumabIpilimumab + Nivolumab 5.12 cPR -65.1 Response until 13.4 months PFS Progression as determined by external assessment A-DL5-21 Uveal Melanoma 2 Valproic acid + Sunitinib Tebentafusp 7.19 cPR -78.8 Response until 12.4 months PFS Non-target lesion progression A-DL5-20 Uveal Melanoma 5 Ipilimumab + PembrolizumabTebentafuspIpilimumab + NivolumabDarovasertib + BinimetinibCamibirstat 8.43 SD -17.6 Disease stabilization until 8.6 months PFS Non-target lesion progression 21 * New since data cut-off on Aug 23, 2024; # has previously been reported as AA-1, patient withdrew consent at data-cut; 1 Transduced viable CD8 T cells; BOR: Best overall response; DL: Dose level; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; PFS: Progression-free survival (censored at data-cut) Data cut-off 07-Apr-2025
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Melanoma Efficacy Population (n=33) Patients with Melanoma Treated with IMA203 in Phase 1b Dose Expansion Patient ID Indication No of prior treatment lines Prior treatments Total infused dose TCR-T cells1 [x109] BOR BOR (Max % change of target lesions) Comment Reason for Progression A-DL5-19 Uveal Melanoma 6 PembrolizumabClinical trial intrahepatic PV10 Ipilimumab + NivolumabClinical trial Anti-CTLA-4 NF AB + XRTCamibirstatPembrolizumab 5.42 cPR -50.9 Response until 8.5 months PFS Non-target lesion progression A-DL5-24 Uveal Melanoma 3 NOX66-005 Idronoxil with radiotherapyDarovasertib + CrizotinibLVGN3616 + LVGN6051 + LVGN7409 + Bevacizumab + Cyclophosphamide 2.89 cPR -48.1 Response until 6.2 months PFS New lesions A-DL5-17 Cut. Melanoma 2 Ipilimumab + Nivolumab+TociliziumabNivolumab + Relatlimab + Tocilizumab + Ipilimumab 4.04 SD -18.6 Disease stabilization until 6.1 months PFS New lesion A-DL5-29 Mucosal Melanoma 2 NivolumabIpilimumab + Nivolumab 7.94 cPR -57.1 Response until 6.0 months PFS Target lesion and non-target lesion progression A-DL5-23 Cut. Melanoma 3 Ipilimumab + NivolumabEncorafenib + BinimetinibRelatlimab + Nivolumab 6.94 cPR -44.8 Response until 6.0 months PFS, patient off study at data-cut due to investigator decision (radiation of one target lesion) A-DL4-05 Cut. Melanoma 4 NivolumabIpilimumab+NivolumabDabrafenib + TrametinibNivolumab 1.63 SD 11.4 Disease stabilization until 5.9 months PFS New lesions, target lesion progression A-DL5-10 Uveal Melanoma 1 SEA-CD40 + Pembrolizumab 2.68 cPR -40.8 Response until 5.8 months PFS Target lesion progression A-DL4-04 Melanoma (Unk. Primary) 1 Ipilimumab + Nivolumab 1.73 SD 0.0 Disease stabilization until 5.7 months PFS New lesion A-DL4-07 Cut. Melanoma 2 Ipilimumab + NivolumabBrektovi + Mektovi + Nivolumab + Relatlimab 1.55 cPR -65.9 Response until 5.7 months PFS New lesions A-DL5-15 Cut. Melanoma 1 Pembrolizumab 3.02 cPR -58.8 Response until 5.6 months PFS New lesions A-DL5-18 Uveal Melanoma 2 TebentafuspIpilimumab + Nivolumab 5.71 SD -25.4 Disease stabilization until 5.5 months PFS New lesion A-DL5-22 Cut. Melanoma 2 Ipilimumab+NivolumabTafinlar + Mekinist 6.31 PR -59.3 Disease stabilization until 2.7 months post infusion, unconfirmed response from 2.7 until 5.5 months PFS New lesion A-DL5-12 Uveal Melanoma 3 Tyrosinase peptides Nivolumab + Ipilimumab + Denosumab Tebentafusp 4.50 SD -22.6 Disease stabilization until 3.5 months PFS Target and non-target lesion progression, new lesion A-DL5-28 Mucosal Melanoma 3 Ipilimumab + NivolumabAvapritinibOpdualag 3.33 PR -36.9 Unconfirmed response until 2.8 months PFS Target lesion progression A-DL5-25 Cut. Melanoma 2 Ipilimumab + NivolumabAxitinib + Nivolumab 5.14 SD 4.6 Disease stabilization until 2.7 months PFS Non-target lesion progression, new lesions A-DL5-33* Cut. Melanoma 4 PembrolizumabPembrolizumabTC TLR7/8 + PembrolizumabBrenetafusp 9.76 SD -11.5 Disease stabilization until 2.1 months PFS New lesion 22 * New since data cut-off on Aug 23, 2024; 1 Transduced viable CD8 T cells; BOR: Best overall response; DL: Dose level; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; PFS: Progression-free survival (censored at data-cut) Data cut-off 07-Apr-2025
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Melanoma Efficacy Population (n=33) Patients with Melanoma Treated with IMA203 in Phase 1b Dose Expansion Patient ID Indication No of prior treatment lines Prior treatments Total infused dose TCR-T cells1 [x109] BOR BOR (Max % change of target lesions) Comment Reason for Progression A-DL5-14 Cut. Melanoma 2 NivolumabEncorafenib + Binimetinib 2.34 PD -41.5 Progressive disease at 1.4 months PFS New lesions A-DL5-35* Uveal Melanoma 2 TebentafuspIpilimumab + Nivolumab 3.71 PD -37.5 Progressive disease at 1.4 months PFS Non-target lesion progression A-DL4-06 Uveal Melanoma 0 NA 2.56 PD -6.3 Progressive disease at 1.4 months PFS New lesion 23 * New since data cut-off on Aug 23, 2024; 1 Transduced viable CD8 T cells; BOR: Best overall response; DL: Dose level; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; PFS: Progression-free survival (censored at data-cut) Data cut-off 07-Apr-2025