EX-99.3 4 dp229416_ex9903.htm EXHIBIT 99.3

Exhibit 99.3

 

Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. Immatics Corporate Presentation May 31, 2025

 

 

Forward - Looking Statement This presentation (“Presentation”) is provided by Immatics N . V . (“Immatics” or the “Company”) for informational purposes only . The information contained herein does not purport to be all - inclusive and none of Immatics, any of its affiliates, any of its or their respective control persons, officers, directors, employees or representatives makes any representation or warranty, express or implied, as to the accuracy, completeness or reliability of the information contained in this Presentation . Forward - Looking Statements . Certain statements in this presentation may be considered forward - looking statements . Forward - looking statements generally relate to future events or the Company’s future financial or operating performance . For example, statements concerning timing of data read - outs for product candidates, the timing, outcome and design of clinical trials, the nature of clinical trials (including whether such clinical trials will be registration - enabling), the timing of IND or CTA filing for pre - clinical stage product candidates, the timing of BLA filings for clinical stage product candidates, estimated market opportunities of product candidates, manufacturing timetables, capacity and success rates, the Company’s focus on partnerships to advance its strategy, and other metrics are forward - looking statements . In some cases, you can identify forward - looking statements by terminology such as “may”, “should”, “expect”, “plan”, “target”, “intend”, “will”, “estimate”, “anticipate”, “believe”, “predict”, “potential” or “continue”, or the negatives of these terms or variations of them or similar terminology . Such forward - looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward looking statements . These forward - looking statements are based upon estimates and assumptions that, while considered reasonable by Immatics and its management, are inherently uncertain . New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties . Factors that may cause actual results to differ materially from current expectations include, but are not limited to, various factors beyond management's control including general economic conditions and other risks, uncertainties and factors set forth in the Company’s Annual Report on Form 20 - F and other filings with the Securities and Exchange Commission (SEC) . Nothing in this presentation should be regarded as a representation by any person that the forward - looking statements set forth herein will be achieved or that any of the contemplated results of such forward - looking statements will be achieved . You should not place undue reliance on forward - looking statements, which speak only as of the date they are made . The Company undertakes no duty to update these forward - looking statements . No Offer or Solicitation . This communication is for informational purposes only and does not constitute, or form a part of, an offer to sell or the solicitation of an offer to sell or an offer to buy or the solicitation of an offer to buy any securities, and there shall be no sale of securities, in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction . No offer of securities shall be made except by means of a prospectus meeting the requirements of Section 10 of the Securities Act of 1933 , as amended, or in an offering exempt from registration . Certain information contained in this Presentation relates to or is based on studies, publications, surveys and the Company’s own internal estimates and research . In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions . Finally, while the Company believes its internal research is reliable, such research has not been verified by any independent source . All the scientific and clinical data presented within this presentation are – by definition prior to completion of the clinical trial and a clinical study report – preliminary in nature and subject to further quality checks including customary source data verification . 2

 

 

PRAME Is Expressed in More Than 50 Cancers ≥95 % ≥10 % 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; IMA203, IM203CD8, IMA402 are being evaluated in separate clinical trials. Cancer Cell Death IMA402 PRAME Bispecific IMA203 PRAME Cell Therapy IMA203CD8 PRAME Cell Therapy (GEN2) Precision targeting of PRAME with 3 clinical product candidates PRAME prevalence in selected indications % PRAME+ patients 1 Indication 95% Cutaneous Melanoma 95% Uterine Carcinoma 95% Uterine Carcinosarcoma 95% Synovial Sarcoma 90% Uveal Melanoma 90% Mucosal Melanoma 85% Ovarian Carcinoma Subtypes 70% Squamous Cell NSCLC 2 65% Triple - negative Breast Carcinoma 45% Small Cell Lung Cancer 45% Esophageal Carcinoma Subtype 40% Kidney Carcinoma Subtype 35% Cholangiocarcinoma 30% HER2 - Enriched Breast Carcinoma 25% Adenocarcinoma NSCLC 2 25% Head & Neck Squamous Cell Carcinoma 20% Hepatocellular Carcinoma 20% Bladder Carcinoma 3 P RAME 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 (…)

 

 

Immatics Is the Global Leader in Precision Targeting of PRAME • PRAME is an intracellular protein presented as a peptide on the surface of tumor cells by HLA molecules 1 • The PRAME peptide can be targeted by T cell receptors (TCRs) engineered by Immatics, thus overcoming limitations of classical antibodies and CAR T - cell therapies not able to access intracellular targets 1,2 • PRAME has multiple functions in tumor biology enhancing tumor cell survival, tumor proliferation and resistance to apoptosis #,3,4 • PRAME expression has been associated with poor prognosis incl. shorter survival 5,6,7,8 • PRAME is homogenously expressed in tumor tissue 9 4 sqNSCLC Ovarian Cancer PRAME RNA detection in tumor samples (ISH) # Activation of proliferative and survival pathways, including PI3K/AKT/mTOR 3 ; # Inhibition of retinoic acid signaling preventing retinoic acid - induced differentiation and apoptosis 4 1 Wermke et al., 2025; 2 Chandran et al., 2019, 3 Yu et al., 2023; 4 Epping et al., 2005; 5 Al - Khadairi & Decock. 2019; 6 Naik et al., 2021; 7 Gezgin et al., 2017; 8 Field et al. 2016; 9 Hukelmann et al. SITC 2022. P RAME

 

 

P h ase P r ec lini c al 1 a 1 b 2 3 Target Indication Modality Product c an d id a t e PRAME 2L Melanoma Cell therapy IMA203 PRAME Uveal melanoma Cell therapy IMA203 PRAME Solid cancers Cell therapy + mRNA - 4203 IMA203 PRAME Gynecologic cancers Cell therapy IMA203CD8 PRAME Other solid cancers PRAME Melanoma, others Bispecific IMA402 MAGEA4/8 HNSCC, sqNSCLC, others Bispecific IMA401 2 COL6A3 COL6A3+ solid cancers Cell therapy IMA204 other Undisclosed Bispecific Undisclosed 3 other Undisclosed Cell therapy Undisclosed 4 other Undisclosed Allogeneic cell therapy IMA30x 5 1 Phase 1a: Dose escalation, Phase 1b: Dose expansion; 2 With or without checkpoint inhibitor (pembrolizumab); 3 mRNA - enabled in vivo expressed TCER® molecules; 4 Immatics’ proprietary ACTallo® platform utilizing Editas’ CRISPR gene editing technology; 2L Melanoma: patients with unresectable or metastatic melanoma who have received at least 1 prior therapy; HNSCC: head and neck squamous cell carcinoma; sqNSCLC: squamous cell non - small - cell lung cancer Product C a nd id a t es Th e r a p e u tic Modalities 3 2 PRAME Franchise 1 Combination P RAME Immatics has the Broadest PRAME Franchise with the Most PRAME Indications and Modalities

 

 

Immatics has the Broadest PRAME Franchise with the Most PRAME Indications and Modalities PRAME Wave #2 PRAME Wave #3 All patient numbers refer to PRAME+/HLA - A*02:01+ patients in the US and EU5 in 2025; Source: Clarivate Disease Landscape and Forecast; EU5: France, Germany, Italy, Spain, United Kingdom; ICI: Immune checkpoint inhibitor; 2L: patients who have received at least 1 prior therapy ~230K addressable PRAME + /HLA - A*02:01 + patients in the US & EU5 p.a. IMA203CD8 PRAME Cell Therapy (GEN2) IMA402 PRAME Bispecific Market entry in advanced melanoma ~9K addressable patients p.a. Expansion to all advanced PRAME cancers ~75K addressable patients p.a. Expansion to early - stage PRAME cancers ~145K addressable patients p.a. • Enhanced pharmacology provides potential to expand to tumor - agnostic label in 2L PRAME solid cancers • First target indications: ovarian cancer, endometrial cancer IMA203CD8 • Next - gen half - life extended bispecific primarily in first - line in combination with ICI and targeted agents • First target indications: melanoma, ovarian cancer, endometrial cancer IMA402 • IMA203 will be Immatics’ first PRAME therapy to enter the market – launch targeted in 2027 • First target indications: 2L cutaneous melanoma, uveal melanoma IMA203 PRAME Wave #1 IMA203 PRAME Cell Therapy 6 P RAME

 

 

Immatics has the Broadest PRAME Franchise with the Most PRAME Indications and Modalities PRAME Wave #1 PRAME Wave #2 PRAME Wave #3 ~230K addressable PRAME + /HLA - A*02:01 + patients in the US & EU5 p.a. IMA203 PRAME Cell Therapy IMA203CD8 PRAME Cell Therapy (GEN2) IMA402 PRAME Bispecific • Ph1a data incl. ovarian cancer: 2025 EXPECTED MILESTONES • Ph1a data in 2L melanoma: 2025 EXPECTED MILESTONES • Ph1b data update at ASCO 2025 • Ph3 interim data analysis 2 : 1Q26 • Ph3 final analysis 2 : 4Q26 • BLA submission: 1Q27 • Launch: 3Q27 EXPECTED MILESTONES S TA TUS S TA TUS S TA TUS • GEN2 PRAME cell therapy leveraging CD8 and CD4 T cells • Enhanced pharmacology • Phase 1 dose escalation ongoing • Off - the - Shelf Bispecific • Next - gen, half - life extended format • Phase 1 dose escalation ongoing • RMAT designation 1 by FDA • Phase 3 SUPRAME trial in patients with advanced melanoma post ICI ongoing; Primary endpoint: PFS for full approval • Phase 1b trial in patients with PRAME cancers ongoing, focus on uveal melanoma 1 Includes all benefits of Breakthrough Therapy Designation; 2 Triggered upon the occurrence of a defined number of events for PFS (progressive disease or death) 7 P RAME

 

 

8 P RAME 1 Target product profile (TPP) in monotherapy in 2L or later settings post SOC at recommended phase 2 dose (“RP2D”). Other factors such as mPFS (median progression free survival) and mOS (median overall survival) may also be considered. LYMPHODEPLETION & INFUSION Tu mor cell H L A Target p e ptide A D MI N I S TR A TION TO PATIENT LEUKAPHERESIS GENETIC E N GIN EE R I N G & EXPANSION TCER® PRODUCTION “OFF - THE - SHELF” PRODUCT PRAME Bispecific Half - life extended (HLE) bispecific T cell engager (TCER®) M o d a lity: Repeat dose App l i c a t i o n : Primarily frontline (+ adjuvant) combination setting P osit i o n in g : Outpatient administration, hospitals and community centers De p l o yme nt : ≥20% cORR, ≥6 months mDOR (monotherapy, last line) TPP at RP2D 1 : PRAME Cell Therapy Autologous TCR T - cell Therapy M o d a lity: Single dose (“one and done”) (no tumor surgery, no high - dose IL - 2) Appli c a t i o n : Primarily second line and later monotherapy setting P osit i o n in g : Administered in specialized academic medical centers; potential for outpatient administration Deployment : ≥40% cORR, ≥6 months mDOR (monotherapy, last line) TPP at RP2D 1 : ACTengine® TC E R® Immatics has the Broadest PRAME Franchise with the Most PRAME Indications and Modalities

 

 

IMA203 PRAME Cell Therapy Market Entry in Advanced Melanoma PRAME Wave #1 9

 

 

IMA203 PRAME Cell Therapy: Market Entry in Advanced Melanoma 10 IMA203 Opportunity ~7.3K ad d r e s s a ble PRAME + /HLA - A*02:01 + patients in the US & EU5 ~1.3K addressable P RA M E + /HLA - A*02:01 + patients in the US & EU5 All patient numbers refer to PRAME+/HLA - A*02:01+ patients in the US and EU5 in 2025; Source: Clarivate Disease Landscape and Forecast; 2L: patients with unresectable or metastatic melanoma who have received at least 1 prior therapy; EU5: France, Germany, Italy, Spain, United Kingdom PRAME Wave #1: IMA203 2L Unresectable or Metastatic Cutaneous Melanoma US EU5 ~3.7K ~3.6K Unresectable or Metastatic Uveal Melanoma US EU5 ~0.6K ~0.7K

 

 

Data cut - off 11 Apr 07, 2025 SUPRAME Phase 3 trial in 2L cutaneous melanoma actively enrolling patients 1 Includes all benefits of Breakthrough Therapy Designation; * PRAME + /HLA - A*02:01 + addressable patient population, source: Clarivate Disease Landscape and Forecast 2025; CRS: cytokine release syndrome; ICANS: immune effector cell associated neurotoxicity syndrome; cORR: confirmed objective response rate; mDOR: median duration of response; mPFS: median progression - free survival; OS: overall survival ; mFU: median follow - up; 2L: patients with unresectable or metastatic melanoma who have received at least 1 prior therapy; EU5: France, Germany, Italy, Spain, United Kingdom; Manufacturing success rate as of Apr 7, 2025 IMA203 PRAME Cell Therapy in Advanced Melanoma Positive Data and High Unmet Need Favorable T ole r ability Mostly mild to moderate CRS Infrequent ICANS (5.4% Gr1, 4.1% Gr2, 4.1% Gr3) No IMA203 - related grade 5 events Potential for outpatient administration Compelling Response Rate cORR: 56% (18/32) 42% (14/33) of patients had deep responses (≥50% tumor size reduction) Encouraging activity in both cutaneous melanoma (cORR 50%) and uveal melanoma (cORR 67%) Durable R es p on s es 12.1 months mDOR and ongoing responses for up to 2.5+ years mPFS of 6.1 months mPFS 12.9 months in patients with deep responses mOS: 15.9 months Rapid & Robust Manufacturing Fast turnaround time: 7 - 8 days + 7 days QC release testing 95% manufacturing success rate to reach target dose Optimized process to achieve desirable cellular functionality Commercial Op p ortuni t y ∼ 9K * addressable patients in US/EU5 in cutaneous and uveal melanoma FDA RMAT designation 1 received in multiple PRAME expressing cancers, including cutaneous and uveal melanoma PRAME Wave #1: IMA203

 

 

IMA203 PRAME Cell Therapy – Patient Journey 12 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; 2 30 mg/m 2 Fludarabine and 500 mg/m 2 Cyclophosphamide for 4 days; 3 1m IU daily days 1 - 5 and twice daily days 6 - 10, total dose is approx. only 5% of the overall dose for high - dose IL - 2 given typically with TIL therapy (Sarnaik et al. 2021 Journal of Clinical Oncology); Manufacturing success rate as of Apr 7, 2025 HLA - A*02:01 Testing Blood sample Treatment & Observation Phase Long Term Follow - up Screening & Manufacturing Phase Manufacturing by Immatics IMA203 One - time infusion Safety and efficacy monitoring for 12 months Lymphodepletion 2 Low dose IL - 2 3 Le u k ap h e r esis as source for cell product Process time of ~14 days 7 - 8 - day manufacturing process applying CD8/CD4 T cell selection 7 - day QC release testing ≥95% of cutaneous melanoma patients are PRAME - positive  no target testing in SUPRAME trial Inclusion by HLA testing only – no PRAME testing required Fast turn - around - time (2 weeks) and manufacturing success rate of 95% Favorable tolerability profile with potential outpatient administration – no high - dose IL - 2 Standard leukapheresis for product manufacturing – no need for tumor biopsy or surgery Prevalence 1 : US: 41%, EU: 48% PRAME Wave #1: IMA203

 

 

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. 13 n=33 57 (31, 79) n=16 62 (32, 74) n=14 54.5 (31, 79) N=74 54 (18, 79) Age, median (range) 48.5 62.5 21.4 52.7 Female, % 39.4 43.8 35.7 51.4 Baseline ECOG status 1, % 2 (0, 6) 2 (0, 6) 2.5 (1, 5) 3 (0, 10) Prior lines of systemic treatment, median (range) 1 (0, 4) 1 (0, 4) 2 (1, 3) --- Prior ICI treatment , median (range) 81 .8/ 5 7 .6 62.5/43.8 100/64.3 --- ≥1 line of PD1/CTLA4 , % --- 62.5 --- --- Prior tebentafusp , % 57.6 56.3 64.3 63.5 Elevated LDH at baseline, % 104.0 101.6 120.5 116.1 Median target lesion sum of diameter, mm (15.0, 309.8) (30.8, 210.0) (15.0, 309.8) (15.0, 309.8) (range) 78.8 93.8 64.3 62.2 Patients with liver metastasis, % 3.0 0.0 0.0 12.2 Patients with brain metastasis, % 0.0 --- 0.0 --- Metastatic staging, % (CM, MM, UkM only) IIIb/IIIc/IVM1a 100.0 --- 100.0 --- IVM1b/c/d Baseline Characteristics Total Safety Population Cutaneous Melanoma Uveal Melanoma All Melanoma Metastatic staging, % (UM only) IVM1a IVM1b/c/d --- --- --- --- 18.8 81.3 --- --- All Melanoma Uveal Melanoma Cutaneous Melanoma Total Safety Population Treatment Experience 4.04 (1.30, 10.20) 3.94 (1.62, 8.43) 4.58 (1.30, 10.20) 2.34 (0.078, 10.20) Infused TCR T cell dose (x10 9 ), median (range) Heavily Pretreated Patient Population Melanoma Efficacy Population Data cut - off Apr 7, 2025 ASCO 2025 PRAME Wave #1: IMA203

 

 

IMA203 PRAME Cell Therapy Safety: Adverse Events Occurring in ≥20% of Patients N=74 Patients Across All Dose Levels in Phase 1a/b (Total Safety Population) 14 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. N = 74 Grade ≥3 Any grade Preferred terms, n (%) 73 (98.6) 73 (98.6) Blood and lymphatic system disorders 67 (90.5) 68 (91.9) Neutropenia 1 38 (51.4) 57 (77.0) Anaemia 27 (36.5) 50 (67.6) Thrombocytopenia 1 38 (51.4) 39 (52.7) Leukopenia 39 (52.7) 39 (52.7) Lymphopenia 2 (2.7) 65 (87.8) Gastrointestinal disorders 0 (0.0) 45 (60.8) Nausea 1 (1.4) 28 (37.8) Diarrhoea 1 1 (1.4) 25 (33.8) Vomiting 0 (0.0) 23 (31.1) Constipation 2 (2.7) 49 (66.2) General disorders and administration site conditions 1 (1.4) 29 (39.2) Fatigue 1 (1.4) 22 (29.7) Pyrexia 0 (0.0) 17 (23.0) Edema peripheral 10 (13.5) 35 (47.3) Investigations 5 (6.8) 29 (39.2) Aspartate aminotransferase increased 7 (9.5) 28 (37.8) Alanine aminotransferase increased 2 (2.7) 15 (20.3) Blood creatinine increased 6 (8.1) 35 (47.3) Skin and subcutaneous tissue disorders 0 (0.0) 18 (24.3) Rash 6 (8.1) 18 (24.3) Rash maculo - popular 6 (8.1) 33 (44.6) Metabolism and nutrition disorders 3 (4.1) 22 (29.7) Hyponatraemia 3 (4.1) 21 (28.4) Hypokalaemia • 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 70 (94.6) CRS, any grade, n (%) 27 (36.5) Grade 1 35 (47.3) Grade 2 8 (10.8) Grade 3 1 0 (0.0) Grade 4 0 (0.0) Grade 5 10 (13.5) ICANS, any grade, n (%) 4 (5.4) Grade 1 3 (4.1) Grade 2 3 (4.1) Grade 3 0 (0.0) Grade 4 0 (0.0) Grade 5 2 (2.7) HLH, any grade, n (%) 0 (0.0) Grade 1 1 (1.4) Grade 2 1 (1.4) Grade 3 0 (0.0) Grade 4 0 (0.0) Grade 5 Data cut - off Apr 7, 2025 ASCO 2025 PRAME Wave #1: IMA203

 

 

IMA203 PRAME Cell Therapy: Best Overall Response in Melanoma Efficacy Population 56% Confirmed Objective Responses in Heavily Pretreated Patients with Metastatic Melanoma 15 *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=33 n=3 n=16 n=14 56% (18/32) 1/3 67% (10/15) 50% (7/14) c ORR 64 % (21/33) 2/3 69% (11/16) 57% (8/14) O R R 91% (30/33) 3/3 88% (14/16) 93% (13/14) DCR Cutaneous Mela n o ma Uveal Mela n o ma Mela n o ma (other) All Mela n o m a 3 Data cut - off Apr 7, 2025 ASCO 2025 PRAME Wave #1: IMA203

 

 

IMA203 PRAME Cell Therapy: Duration of Response in Melanoma Efficacy Population Prolonged Ongoing Responses up to 2.5+ Years after Treatment 16 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 Ongoing Scans at approximately week 6, month 3 and then every 3 months All Melanoma 3 n=33 Uveal Melanoma n=16 Cutaneous Melanoma n=14 12.1 (1.8+, 32.6+) 13.4 11.0 (1.8+, 31.6) 13.4 NR (4.2, 32.6+) 16.7 mDOR [mo], (range) mFU [mo] PRAME Wave #1: IMA203

 

 

IMA203 PRAME Cell Therapy: Survival Outcomes in Melanoma Efficacy Population 17 Median Progression Free Survival Median Overall Survival Data cut - off Apr 7, 2025 ASCO 2025 All 1 Melanoma n=33 Uveal Me l a n o ma n=16 C u t ane o u s Me l a n o ma n=14 6.1 (1.4, 34.0+) 14.4 8.5 (1.4, 32.9) 8.7 6.0 (1.4 , 34.0+) 14.4 mPFS [mo] (range) mFU [mo] All 1 Melanoma n=33 Uveal Me l a n o ma n=16 C u t ane o u s Me l a n o ma n=14 15.9 (2.4, 34.2+) 14.4 16.2 (3.2+, 34.2+) 14.5 13.9 (2.4, 34.0+) 14.4 mOS [mo] (range) mFU [mo] 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. PRAME Wave #1: IMA203

 

 

IMA203 Phase 1b in Melanoma: Overview of Studies PFS and OS Data in Melanoma Cohorts mOS (months) mPFS (months) Prior lines of therapies Melanoma patient population N Phase Drug Product 15.9 6.1 3% n=0, 24% n=1, 30% n=2, 24% n=3:, 6% n=4, 6% n=5, 6% n=6 82% received prior ICI (median of 1 prior line of ICI in overall population, median of 2 prior lines of ICI in cut. melanoma) Median of 2 prior lines, median of 2.5 prior lines in cut. melanoma 42% cutaneous 48% uveal 9% other 33 1b (Dose Expansion) IMA203 in Melanoma 6.3 2.6 0% n=1, 27% n=2, 73% n>2 prior lines 100% received prior CPI (median of 2 prior lines of CPI, median of 2.5 prior lines of CPI in cut. melanoma) Median of 4 prior lines, median of 4.5 prior lines in cut. melanoma 73% cutaneous 18% uveal 9% other 11 1a (Dose Escalation) IMA203 in Melanoma 5.3 2.5 0% n=1, 16% n=2, 84% n>2 prior lines 100% received prior CPI (median 3 prior lines of CPI) Median of 4 prior lines, median of 4.5 prior lines in cut. melanoma 63% cutaneous 11% uveal 26% other 19 1a (Dose Escalation) IMA201/202/203 combined in Melanoma 13.9 4.1 median of 3 prior lines (min/max: 1/9) 100% received prior CPI 54% cutaneous 0% uveal 45% other 153 2 Lifileucel (C - 144 - 01, Cohort 2+4) 1 11.6 2.9 57% n=1, 27% n=2, 12% n>2 prior lines 99% received prior CPI 85% cutaneous 0% uveal 15% other 238 3 Tilsotolimod + Ipilimumab (ILLUMINATE - 301) 2 14.7 2.1 46% n=1, 35% n=2, 19% n≥3 prior lines 99% received prior CPI 68% cutaneous 0% uveal 32% other 354 1/2 Nivolumab + Relatlimab (RELATIVITY - 020, D1 Cohort) 3 Data cut - off Apr 7, 2025 18 1 Chesney et al., 2022; 2 Diab et al., 2024; 3 Ascierto et al., 2023 PFS: progression - free survival; OS: overall survival; CPI: checkpoint inhibitor 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. PRAME Wave #1: IMA203

 

 

IMA203 PRAME Cell Therapy Enhanced mPFS of >1 Year in Melanoma Patients with Deep Responses Data cut - off Apr 07, 2025 19 • 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 mFU mPFS n ND 2.6 11 Dose Escalation IMA203 8.7 5.8 19 Dose Expansion IMA203 <50% tumor size reduction (inlcuding tumor size increase) 19.5 12.9 14 Dose Expansion IMA203 ≥50% tumor size reduction Log - rank: 0.019 ND, not defined; mFU, median follow - up; mPFS, median progression - free survival. PRAME Wave #1: IMA203

 

 

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 IMA203 n=180 Investigator’s choice n=180 Primary Endpoint • P F S Key Secondary Endpoint • Overall survival Ra nd o mi z at i o n 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 upo n t h e o ccu r ren c e o f a d e fin e d nu m b e r o f even t s fo r PFS (p r o g ressiv e d i s e a s e o r de a t h ) ; ICI: i mm un e ch e c k p o in t inhib it or ; PFS: p r o g ressio n - fre e surviv a l ; ORR : o bj e c t iv e respon s e r a t e ; TESA E s : t re a t m ent - e m er g en t s e riou s 20 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 analysis 1 Q4 2026 Final analysis 2 Q1 2027 BLA submission Q3 2027 La u n c h PRAME Wave #1: IMA203

 

 

Cell Therapy Manufacturing Facility To Support IMA203 BLA and Commercialization 21 • ~100,000 sq ft state - of - the - art research & GMP manufacturing facility • Modular design for efficient and cost - effective scalability - total of 8 manufacturing suites, plus further expansion space • Capacity sufficient to serve early - stage and registration - directed clinical trials as well as planned commercial supply • In - house manufacturing and QC allows full control of process, product and costs • Located in the Houston Metropolitan Area, Texas, offering economic labor and operating costs and talent pool highly qualified in cell therapy manufacturing & QC BLA: Biologics License Application PRAME Wave #1: IMA203

 

 

IMA203CD8 PRAME Cell Therapy (GEN2) Expansion to all Advanced PRAME Cancers PRAME Wave #2 22

 

 

IMA203CD8 PRAME Cell Therapy (GEN2): Expansion of Commercial Opportunity to all Advanced PRAME Cancers 23 IMA203CD8 Opportunity 2L Solid Tumors All patient numbers refer to PRAME + /HLA - A*02:01 + patients in the US and EU5 in 2025; Source: Clarivate Disease Landscape and Forecast; EU5: France, Germany, Italy, Spain, United Kingdom 1 Bajwa et al. 2021 Journal for Immunotherapy of Cancer; 2 Melenhorst et al. 2022 Nature, Bai et al. 2022 Science Advances; 2L: patients with unresectable or metastatic melanoma who have received at least 1 prior therapy; sqNSCLC: squamous cell non - small - cell lung cancer, HNSCC: head and neck squamous cell carcinoma The PRAME + /HLA - A*02:01 + addressable patient opportunity incl. indications with both high and medium - level PRAME expression is ~ 75K per year • Co - transduction of CD8αβ alongside PRAME TCR adds functional CD4 + T cells designed to boost cytotoxicity • Proof of concept from preclinical experiments 1 and CD19 CAR T cell studies in leukemia 2 • First clinical data with IMA203CD8 in Phase 1a dose escalation indicates potential for deeper responses and targeting both high and medium - level PRAME indications EU5 US 2K 2K Ovarian 2K 2K Uterine 10K 7K sqNSCLC 2K 2K HNSCC 8K 5K Breast 18K 16K Others TUMOR CELL DEATH CD 8 - engin e e r ed CD4 T CELL Cytotoxic Activity CD8 T CELL T cell H elp C yt o t o x ic Activity CD8 PR A M E T CR PRAME Wave #2: IMA203CD8

 

 

24 Data cut - off Sep 30, 2024 SITC 2024 Dose escalation ongoing to investigate full clinical potential in hard - to - treat solid tumors outside of melanoma Tolerability Manageable tolerability ≥Grade 3 AEs mainly expected cytopenia DLTs at DL4b led to dose adjustment to DL4a Adjustments to DL4a dosing and criteria enable higher dose exploration Ongoing dose escalation to reach RP2D, both in melanoma and indications outside melanoma Deep and durable objective responses at low doses 41% (14/34) cORR (at presumably suboptimal doses) 84% (32/38) of patients had tumor shrinkage; two patients with complete response of target lesions 9.2 months mDOR with 3 confirmed responses ongoing at 1+ years Activity & Duration of Response Development Potential Focus on indications with both high and medium - level PRAME expression startin CD g 8 with gynecologic cancers Pursue tumor - agnostic label in PRAME+ cancers to leverage full breadth of PRAME, incl. NSCLC, triple - negative breast cancer, others Possibility to administer IMA203CD8 without post - infusion IL - 2 AE: adverse event; DLT: dose - limiting toxicity; RP2D: recommended phase 2 dose; cORR: confirmed objective response rate; mDOR: median duration of response; NSCLC: non - small - cell lung cancer IMA203CD8 PRAME Cell Therapy (GEN2) Summary: Clinical Data & Next Steps PRAME Wave #2: IMA203CD8

 

 

IMA203CD8 PRAME Cell Therapy (GEN2) – Patient Characteristics 25 1 DL4a cleared in Dec 2023; 2 DLTs at DL4b triggered modifications of the eligibility criteria, adapted patient population is treated with DL4c; 3 All patients who started lymphodepletion. 4 All infused patients with at least one tumor assessment postbaseline. Data cut - off Sep 30, 2024 SITC 2024 DL4a 1 (N=33) Cleared for safety, defined as provisional MTD Dose Escalation with and without IL - 2 ongoing DL4b (N=4) Phase 1a Dose Escalation DL3 (N=5) Efficacy Population Total Safety Population N=41 4 N=44 3 Number of patients 3 (0, 8) 3 (0, 8) Prior lines of systemic treatment (median, min, max) 43.9 47.7 LDH at baseline >1 x ULN [% of patients] 83.0 (12.4, 434.4) 84.5 (12.4, 434.4) Baseline tumor burden Median target lesion sum of diameter [mm] (min, max) 43.9 45.5 With liver/brain lesions at baseline [% of patients] DL3: 0.2 - 0.48 DL4a: 0.481 - 0.8 DL4b: 0.801 - 1.2 DL4c 2 : 0.801 - 1.2 DL3: 0.2 - 0.48 DL4a: 0.481 - 0.8 DL4b: 0.801 - 1.2 DL4c 2 : 0.801 - 1.2 Infused dose levels TCR - T cells/m 2 BSA [x10 9 ] 1.47 (0.44, 2.05) 1.48 (0.44, 2.05) Total infused dose TCR - T cells [x10 9 ] (median, min, max) PRAME Wave #2: IMA203CD8 DL4c 2 Without IL - 2 (N=2) DL4c 2 With IL - 2 (pl a nn ed)

 

 

Tolerability of IMA203CD8 PRAME Cell Therapy (GEN2) 26 All ≥Grade 3 Adverse Events (N=44) 2.3 1 Immune effector cell - associated neurotoxicity syndrome 100.0 44 Blood and lymphatic system disorders 90.9 40 Neutropenia 56.8 25 Anaemia 56.8 25 Lymphopenia 34.1 15 Thrombocytopenia 25.0 11 Leukopenia 4.5 2 Febrile neutropenia 20.5 9 Investigations 11.4 5 Alanine aminotransferase increased 11.4 5 Aspartate aminotransferase increased 2.3 1 Hyperglycaemia 2.3 1 Hypermagnesaemia 2.3 1 Hypoalbuminaemia 11.4 5 General disorders and administration site conditions 11.4 5 Fatigue 2.3 1 Oedema peripheral Musculoskeletal and connective tissue disorders 5 11.4 TEAEs by maximum severity for all patients (N=44) e 3 ≥ Grad Adverse event rade 3 ≥ G Adverse event % No. ( System organ class , preferred term) % No. ( System organ class , preferred term) … table continued 100.0 44 Patients with any adverse event 9.1 4 Immune system disorders 15.9 7 Adverse events of special interest 9.1 4 Haemophagocytic lymphohistiocytosis 2 13.6 6 Cytokine release syndrome 1 9.1 4 Infections and infestations 4.5 2 Pneumonia 2.3 1 Infection 2.3 1 Sepsis 3 2.3 1 Systemic candida 6.8 3 Gastrointestinal disorders 4.5 2 Diarrhoea 2.3 1 Abdominal pain 6.8 3 Skin and subcutaneous tissue disorders 2.3 1 Alopecia 4.5 2 Blood creatinine increased 2.3 1 Rash maculo - papular 2.3 1 Blood alkaline phosphatase increased 6.8 3 Vascular disorders 2.3 1 Blood bilirubin increased 6.8 3 Hypertension 2.3 1 Gamma - glutamyltransferase increased 4.5 2 Nervous system disorders 13.6 6 Metabolism and nutrition disorders 2.3 1 Neurotoxicity 2 4.5 2 Hypophosphataemia 2.3 1 Syncope 2.3 1 Acidosis 4.5 2 Renal and urinary disorders 2.3 1 Decreased appetite R a s h 2 4.5 2.3 1 Acute kidney injury 2.3 1 Urinary tract obstruction 2.3 1 Hepatobiliary disorders 2.3 1 Hepatic function abnormal 2.3 1 Reproductive system and breast disorders 2.3 1 Pelvic pain All treatment - emergent adverse events (TEAEs) with ≥ Grade 3 regardless of relatedness to study treatment that occurred in at least 1 patient are presented; 1 DLT: Dose limiting toxicity in patient DL4b - 04. 2 DLTs in patient DL4b - 01; CRS: cytokine release syndrome, HLH: hematophagocytic lymphohistiocytosis • 6.8 3 Bone pain 4.5 2 Myalgia 4.5 2 Back pain 2.3 1 Arthralgia • Overall manageable tolerability profile • Expected cytopenias • Mostly mild to moderate CRS:  36% (16/44) Grade 1  48% (21/44) Grade 2  11% (5/44) Grade 3  2% (1/44) Grade 4 • DLTs in 2 patients at DL4b as previously reported by the Company:  Patient DL4b - 01: high in vivo T cell expansion, Grade 4 neurotoxicity, Grade 4 CRS, Grade 3 HLH  Patient DL4b - 04: Grade 3 CRS defined by Grade 3 ALT resolved to Grade 2 within 10 days; no need for vasopressors or ventilation 3 • No IMA203CD8 - related patient death • Consecutive modification of inclusion/exclusion criteria + IL - 2 scheme Dose escalation ongoing based upon manageable tolerability in patients at DL4a 3 Possibly related Grade 5 event as previously reported was determined by the PI to be unlikely related to IMA203CD8 after complete assessment. Patient died from sepsis that was aggravated by immunosuppression from Flu/Cy (possibly related), high grade HLH event, the toxicity management and the fast - progr essive disease PRAME Wave #2: IMA203CD8 Data cut - off Sep 30, 2024 SITC 2024

 

 

Clinical Anti - Tumor Activity of IMA203CD8 PRAME Cell Therapy (GEN2) (N=41) Ongoing Dose Escalation 27 41% (14/34) c O R R 9.2 months 2.0+, 23.5+ 13.1 months median DOR (min, max) m FU 10/17 responses ongoing including 3 confirmed responses at 1+ year Deep responses with ≥50% tumor size reduction in 11/17 responders incl. 2 patients with complete response of target lesions 41% (17/41) O R R 84% (32/38) Tumor shrinkage 3 85% (34/40) DCR 4 (at week 6) ongoing * Maximum change of target lesions and RECIST1.1 response at different timepoints; 1 Patients off study at data - cut; 2 Metabolic CR according to PET - CT; 3 Three patients excluded from tumor shrinkage analysis and figures due to lack of post - treatment assessment; 4 One patient had an early tumor assessment, outside the first assessment visit window and is not included in DCR calculation. Initial ORR: Objective response rate according to RECIST 1.1 at any post infusion scan; Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with at least two available post infusion scans or patients with progressive disease (PD) at any prior timepoint, patients with ongoing unconfirmed PR not included in cORR calculation; Duration of response (DOR) in confirmed responders is defined as time from first documented response until disease progression/death. Patients with ongoing response will be censored at date of data cut - off. Median DOR is analyzed by using the Kaplan - Meier method; Median Follow - up (mFU) is analyzed by using the reverse Kaplan - Meier method; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; CR: complete response; BL: Baseline; BOR: Best Overall Response; DCR: disease control rate; NSCLC: non - small - cell lung cancer PRAME Wave #2: IMA203CD8 Data cut - off Sep 30, 2024 SITC 2024

 

 

Duration of IMA203CD8 PRAME Cell Therapy (GEN2) Therapy Responses (N=41) Ongoing Dose Escalation 28 1 Metabolic complete response (CR) according to PET - CT 2 Patients off study at data - cut; 3 three patients excluded from tumor shrinkage analysis and figures due to lack of post - treatment assessment; 4 one patient had an early tumor assessment, outside the first assessment visit window and is not included in DCR calculation. 41% (14/34) c O R R 9.2 months 2.0+, 23.5+ 13.1 months median DOR (min, max) m FU 10/17 responses ongoing including 3 confirmed responses at 1+ year Deep responses with ≥50% tumor size reduction in 11/17 responders incl. 2 patients with complete response of target lesions 41% (17/41) O R R 84% (32/38) Tumor shrinkage 3 85% (34/40) DCR 4 (at week 6) Initial ORR: Objective response rate according to RECIST 1.1 at any post infusion scan; Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with at least two available post infusion scans or patients with progressive disease (PD) at any prior timepoint, patients with ongoing unconfirmed PR not included in cORR calculation; Duration of response (DOR) in confirmed responders is defined as time from first documented response until disease progression/death. Patients with ongoing response will be censored at date of data cut - off. Median DOR is analyzed by using the Kaplan - Meier method; Median Follow - up (mFU) is analyzed by using the reverse Kaplan - Meier method; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; BL: Baseline; BOR: Best Overall Response; DOR: Duration of Response; DCR: disease control rate; NSCLC: non - small - cell lung cancer O ngoi n g PRAME Wave #2: IMA203CD8 Data cut - off Sep 30, 2024 SITC 2024

 

 

Opportunity of IMA203CD8 in Medium - Level PRAME Expressing Indications 29 * Patients treated at RP2D during Ph1b with evaluable post baseline assessments at data - cut off IMA203: Aug 23, 2024; BOR: best of response; PD: progressive disease; SD: stable disease; (c)PR: (confirmed) partial response; sqNSCLC: squamous cell non - small - cell lung cancer N=38 N=39* Number of patients 1.48 (0.443, 2.05) 5.09 (1.0, 10.2) Total infused dose TCR - T cells [x10 9 ] Deep responses with IMA203CD8 at low doses - 30% to - 50% - 50% to - 85% - 85% to - 100% PRAME expression level associates with IMA203 and IMA203CD8 activity Potential for targeting medium - level PRAME expressing tumors with IMA203CD8 IMA203CD8 offers similar responses at 1.5 x 10 9 total infused dose to those demonstrated by IMA203 at 3x higher dose. With higher doses currently being explored, IMA203CD8 may offer an enhanced opportunity to treat cancers with both high and medium - level PRAME expression including ovarian cancer, uterine cancer, sqNSCLC, triple - neg. breast cancer and others. Next clinical data update including focus on ovarian cancer in 2025 . PRAME Wave #2: IMA203CD8 Data cut - off Sep 30, 2024 SITC 2024

 

 

IMA402 PRAME Bispecific Expansion to Early - Stage PRAME Cancers PRAME Wave #3

 

 

31 IMA402 Opportunity All patient numbers refer to PRAME + /HLA - A*02:01 + patients in the US and EU5 in 2025; Source: Clarivate Disease Landscape and Forecast; EU5: France, Germany, Italy, Spain, United Kingdom; sqNSCLC: squamous cell non - small - cell lung cancer 1L Solid Tumors ~145K addressable P R AM E + /HLA - A*02:0 1 + patients in the US & EU5 • Off - the - shelf biologic for immediate treatment • Antibody - like properties: half - life extended (HLE) format with enhanced stability, t 1/2 1+ week(s) • Repeat dosing • Patient reach also into community setting IMA402 PRAME Bispecific: Expansion of the Commercial Opportunity to Early - Stage PRAME Cancers TCR Bispecifics (TCER®) 2 1 3 L o w - a ffinity T cell recruiter against CD3/TCR Fc part for half - life extension, favorable stability and ma n u f actu r a b ili t y High - affinity TCR domains targeting XPRESIDENT® - selected tumor - specific peptide - HLA molecules EU5 US 6K 6K Cut. Melanoma 9K 7K Ovarian 6K 6K Uterine 17K 12K sqNSCLC 10K 7K Breast 32K 25K Others PRAME Wave #3: IMA402

 

 

C a nc er Cell IMA402 PRAME Bispecific Summary: Phase 1 Dose Escalation Study 32 Dose escalation in advanced stage indications at higher DLs ongoing Tolerability Favorable tolerability profile Most common treatment - related AEs are low - grade CRS and transient lymphopenia Early dose escalation ongoing Initial clinical signal observed depending on target expression and TCER® dose Pharmacokinetics Median half - life of ~7 days Potential for: • Bi - weekly dosing • Combination with CPIs Activity D e v elo p m e n t Potential Primarily frontline (and adjuvant) settings in combination with checkpoint inhibitors and targeted agents • Near - term: 1L melanoma • Mid - term: Gynecologic AE: adverse event; CRS: Cytokine release syndrome; CPI: checkpoint inhibitor Data cut - off Nov 6, 2024 P RAME cancers, others Multiplexing with Bispecifics against other targets, such as MAGEA 4 / 8 TCER® IMA 402 PRAME Wave #3: IMA402

 

 

Phase 1/2 Clinical Trial to Evaluate IMA402 PRAME Bispecific D L1 D L2 D L3 D L4 D L5 D L7 D L9 D L6 t bd 20 µg 60 µg 120 µg 360 µg 800 µg 1600 µg 3000 µg 4000 µg 5000 µg D L8 • MABEL - based starting dose • Dose escalation based on cohorts of 1 - 6 patients using adaptive design (BLRM model) • Weekly infusions 2 with potential to explore less frequent dosing based on PK data Key Eligibility Criteria Object iv es Primary: • Determine MTD and/or RP2D • Tolerability Secondary: • Initial anti - tumor activity • Pharmacokinetics • Recurrent and/​or refractory solid tumors 1 • HLA - A*02:01 positive • ECOG status 0 - 1 • Received or not eligible for all available indicated standard of care treatments Total safety population (N=33) • MTD not yet determined • Dose escalation ongoing at DL11 (12 mg) as of May 13, 2025 33 1 Cutaneous melanoma, uveal melanoma, synovial sarcoma, endometrial cancer, ovarian cancer, squamous cell non - small cell lung cancer; 2 Step dosing introduced at DL4; Low - dose dexamethasone used as preventive measure for initial doses as applied for other bispecific T cell engagers; Clinicians can increase patient’s dose to previously cleared dose levels; MTD: maximum tolerated dose, RP2D: recommended phase 2 dose; BLRM: Bayesian logistic regression model PRAME Wave #3: IMA402 Data cut - off Nov 6, 2024

 

 

34 IMA402 PRAME Bispecific Demonstrates Favorable Tolerability in N=33 Patients Most Frequent Related AEs were Lymphopenia and CRS ≥ Grade 3 All Grades TEAEs, n [%] 17 [52] 33 [100] Any 15 [45] 32 [97] Treatment - related ≥ Grade 3 All Grades Treatment - related AEs 1 , n [%] 10 [30] 17 [52] Lymphopenia 1 [3] 16 [48] Cytokine release syndrome 0 9 [27] Arthralgia 0 9 [27] Fatigue 0 7 [21] Pruritus 0 7 [21] Rash 2 [6] 6 [18] Aspartate aminotransferase increased 1 [3] 5 [15] Alanine aminotransferase increased 0 5 [15] Pyrexia 2 [6] 4 [12] Anaemia 0 4 [12] Vomiting 0 3 [9] C - reactive protein increased 0 3 [9] Headache 0 3 [9] Rash maculo - popular 2 [6] 2 [6] Neutropenia 1 [3] 2 [6] Stomatitis 1 [3] 1 [3] Blood creatinine increased 1 [3] 1 [3] Electrocardiogram abnormal 1 [3] 1 [3] Gamma - glutamyltransferase increased 1 [3] 1 [3] Hypertension 1 [3] 1 [3] Immune - mediated arthritis 1 [3] 1 [3] Tumor lysis syndrome 1 [3] 1 [3] Tumor pain • Data here includes patients up to DL8 • Favorable tolerability profile • Most frequent/relevant related AEs were • transient lymphopenia, • mostly mild to moderate CRS (42% Grade 1, 3% Grade 2, 0% Grade 3, 3% Grade 4), majority at first dose • one DLT: Grade 4 CRS (fully resolved) • No IMA402 - related Grade 5 events • As of May 13, dose escalation remains ongoing at DL11 (12 mg) • MTD not reached 1 All treatment - emergent adverse events (TEAEs) at least possibly related to IMA402 infusion with grade 1 - 2 occurring in at least 9% of patients and all events with grade 3 - 5; CRS: Cytokine release syndrome; MTD: Maximum tolerated dose; DLT: dose limiting toxicity; One AE “Rash, Intermittent” was not coded at data cut - off, but added to the preferred term “Rash” Data cut - off Nov 6, 2024 PRAME Wave #3: IMA402

 

 

Positive/NT Negative PRAME Status 7+ * 1 - 6 Across DLs Dose Levels 78% 25% 14% Patients with Tumor Shrinkage Early Signs of Clinical Activity Associated with PRAME Expression and IMA402 Dose 35 BOR (RECIST 1.1) Ongoing response / SD (RECIST1.1/ iRECIST) Data cut - off Nov 6, 2024 * Patients who received DL7 or higher, either from start or as part of intra - patient dose - escalation; # continuing treatment; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; BOR: Best Overall Response; BL: Baseline; NT: not tested or not evaluable for PRAME expression # # • Melanoma patient with confirmed partial response ongoing at 3 months (DL7, see next slide) • Melanoma patient with - 27.5% tumor shrinkage at first scan (DL8) • Uveal melanoma patient with - 25.0% tumor shrinkage deepening over time (started at DL4 and currently at DL7, see next slide) • Ovarian cancer patient with - 13% tumor shrinkage ongoing at 3 months (started at DL6 and currently at DL7) • Next update on Phase 1a with data at relevant dose levels in second - line and later melanoma planned in 2025 PRAME Wave #3: IMA402

 

 

Exemplary Patient Cases Suggesting Dose - Dependent Tumor Response 36 Data cut - off Nov 6, 2024 BOR: Best Overall Response; SD: Stable Disease; cPR: Confirmed Partial Response; arrow: Ongoing response / stable disease (RECIST 1.1/ iRECIST) Patients with Disease Control (RECIST1.1) at Relevant Doses (DL7+) Case 1 Case 2 DL 7 DL 7 Patient Characteristics & Outcomes 52 - year - old female with cutaneous melanoma Lesions in lung, lymph nodes, gall bladder, fat tissue, pancreas 1 prior line of therapy and maintenance with anti - PD - 1 Patient received DL7 from start (after step - up dosing) Ongoing cPR at 3 months post treatment start with - 40.2% reduction of target lesion size Patient Characteristics & Outcomes 46 - year - old female with uveal melanoma Lesions in liver 3 prior lines of therapy with anti - PD1 and tebentatafusp Patient received DL4 and went up to DL7 through intra - patient dose escalation Ongoing SD at 8+ months post - treatment start with - 25% reduction of target lesion size PRAME Wave #3: IMA402

 

 

IMA401 MAGEA4/8 Bispecific Driving Innovation beyond PRAME beyond PRAME

 

 

Beyond the PRAME Franchise PRAME Wave #1 PRAME Wave #2 PRAME Wave #3 ~230K addressable PRAME + /HLA - A*02:01 + patients in the US & EU5 p.a. IMA203 PRAME Cell Therapy IMA203CD8 PRAME Cell Therapy (GEN2) IMA402 PRAME Bispecific ~62K addressable MAGEA4/8+ and HLA - A*02:01+ in the US & EU5 p.a. EXPECTED MILESTONES • IMA401 Ph1a data with head & neck cancer focus: 2025 • IMA401 Ph1a data with NSCLC focus: 2026 IMA401 beyond PRAME • Bispecific targeting MAGEA4/8 • IMA401 in 1L sqNSCLC, HNSCC, bladder cancer & others • Advancement of mRNA - encoded TCER® molecules in collaboration with Moderna 38

 

 

IMA401 MAGEA4/8 Bispecific: Driving Innovation beyond PRAME 39 IMA401 Opportunity 1L Solid Tumors 1 Target prevalence is based on TCGA RNAseq data combined with a proprietary mass spec - guided RNA expression threshold; All patient numbers refer to MAGEA4/8 + /HLA - A*02:01 + patients in the US and EU5 in 2025; Source: Clarivate Disease Landscape and Forecast; EU5: France, Germany, Italy, Spain, United Kingdom; sqNSCLC: squamous non - small - cell lung cancer, HNSCC: head and neck squamous cell carcinoma The MAGEA4/8 + and HLA - A*02:01 + addressable patients in the selected indications is ~62K per year ~26K US: ~36K EU5: Beyond PRAME: IMA401 EU5 US 13K 9K sqNSCLC 4K 3K HNSCC 6K 3K Bladder 13K 11K Others 52% sqNSCLC: MAGEA4/8 target 36% HNSCC: prevalence 1

 

 

C a nc er Cell MAGEA4/8 IMA401 MAGEA4/8 Bispecific Summary: Phase 1 Dose Escalation Study 40 AE: Adverse Event; CRS: Cytokine Release Syndrome; (c)ORR: (confirmed) objective response rate; PR: Partial Response; DCR: disease control rate; CPI: checkpoint inhibitors; q4w: once every four weeks; HNSCC: Head and neck squamous cell carcinoma; sqNSCLC: squamous cell non - small - cell lung cancer Data cut - off Jul 23, 2024 ESMO 2024 Durable ongoing PRs of up to 13+ months 53% (9/17) DCR Tumor shrinkage in 53% (8/15) of patients Deep responses (tumor shrinkage of ≥ 50%) in four patients with deepening of responses observed over time Tolerability Activity & Duration of Response 29% (5/17) ORR and 25% (4/16) cORR in patients with MAGEA4/8 high expression at relevant doses • Mid - term: sqNSCLC, bladder and other squamous solid cancers Multiplexing with other T cell engagers , e.g., IMA402 (PRAME) D e v elop m e n t Potential Primarily frontline (and adjuvant) settings in combination with checkpoint inhibitors and targeted agents • Near - term: HNSCC Most common treatment - related AEs are low - grade CRS, transient lymphopenia and neutropenia Pharmacokinetics Median terminal half - life of 16.9 days Potential for: • Flexibility in dosing schedules • Combination with CPIs • Increasing dosing intervals to q4w Monotherapy and checkpoint inhibitor combination dose refinement ongoing TCER® IMA401 Beyond PRAME: IMA401

 

 

41 180 µg 540 µg 1800 µg 2500 µg Key Eligibility Criteria Object iv es Primary: • Determine MTD and/or RP2D Secondary: • Tolerability • Pharmacokinetics • Initial anti - tumor activity • Recurrent and/​or refractory solid tumors • HLA - A*02:01 positive • MAGEA4/8 - positive as confirmed by mRNA - based assay 3 • ECOG status 0 - 2 • Received or not eligible for all available indicated standard of care treatments 60 µg 1200 µg 20 µg 6.6 µg • MTD not yet determined • Dose escalation ongoing to optimize dosing intervals and schedule Total safety population (N=35) • MABEL - based starting dose • Dose escalation based ​on cohorts of 1 - 6 patients using ​adaptive design (BLRM model) • Four initial q1w step dosings 1 up to target dose, q2w after reaching target dose 2 Trial Design – IMA401 - 101 Phase 1a Dose Escalation First - in - Human Basket Trial Targeting the MAGEA4/8 Peptide in Solid Tumors 1 Step dosing with 300 µg and 600 µg introduced at DL6; Low - dose dexamethasone pre - medication used at higher dose levels as used with other approved bispecific products has been implemented as preventive measure for continued dose escalation; Patients can increase their dose to previously cleared dose levels; 2 q2w: once every two weeks, weekly (q1w) dosing was applied up to DL5; 3 IMADetect®: proprietary mRNA - based assay using Immatics’ MS - guided threshold; BLRM: Bayesian logistic regression model; MTD: Maximum tolerated dose. D L1 D L2 D L3 D L4 D L5 D L6a D L7 D L6 t bd 2000 µg D L6b Beyond PRAME: IMA401 Data cut - off Jul 23, 2024 ESMO 2024

 

 

42 IMA401 MAGEA4/8 Bispecific Demonstrates Manageable Tolerability (N=35) Most Frequent Related AEs were Lymphopenia, CRS and Neutropenia ≥ Grade 3 All Grades TEAEs, n [%] 26 [74] 32 [91] Any 19 [54] 28 [80] Treatment - related ≥ Grade 3 All Grades Treatment - related AEs 1 , n [%] 11 [31] 12 [34] Lymphopenia 0 11 [31] Cytokine release syndrome 5 [14] 8 [23] Neutropenia 2 [6] 6 [17] Facial pain 4 [11] 5 [14] Anaemia 2 [6] 5 [14] Thrombocytopenia 1 [3] 5 [14] Headache 2 [6] 4 [11] Hypertension 2 [6] 4 [11] Leukopenia 0 4 [11] Fatigue 0 3 [9] Nausea 1 [3] 2 [6] Hypoxia 1[3] 1 [3] Aspartate aminotransferase increased 1[3] 1 [3] Febrile neutropenia 1[3] 1 [3] Pneumonia 1[3] 1 [3] Sinus tachycardia • Overall manageable tolerability profile • Most frequent/relevant related AEs were • transient lymphopenia • mild to moderate CRS (23% Grade 1, 9% Grade 2, no Grade ≥ 3 ), majority at first dose • neutropenia 2 occurred mostly at initial target dose and fully resolved in all cases except one (see below) • one possibly related death (pneumonia in the context of lung tumor progression and concurrent neutropenia) as previously reported 3 • MTD not reached based on the BLRM 1 All treatment - emergent adverse events (TEAEs) at least possibly related to IMA401 infusion with grade 1 - 2 occurring in at least 9% of patients and all events with grade 3 - 5; 2 with three dose - limiting events at 2.5 mg (DLT), neutropenia observed in patients with and without dexamethasone pre - medication; 3 reported in Annual Report 2023, patient did not receive dexamethasone pre - medication; CRS: Cytokine Release Syndrome; BLRM: Bayesian logistic regression model; MTD: Maximum tolerated dose Beyond PRAME: IMA401 Data cut - off Jul 23, 2024 ESMO 2024

 

 

1 Patients in this analysis had received IMA401 infusions at ≥1 mg and showed MAGEA4/8 target expression above indicated MAGEA4/A8 high qPCR threshold (n=17); PD: Progressive disease; PR: Partial response; cPR: confirmed Partial response; SD: Stable disease. Objective Responses are Associated with Target Expression Exploratory Analysis in Patients with MAGEA4/8 high Expression at Relevant IMA401 Doses (DL6 - 7; N=17) 43 qPCR - threshold MAGEA4/8 high qPCR - threshold for patient screening MAGEA4/8 RNA expression in pre - treatment biopsies relative to t h r es ho ld N=17 patients with relevant IMA401 doses and MAGEA4/8 high levels 1 Beyond PRAME: IMA401 Data cut - off Jul 23, 2024 ESMO 2024

 

 

IMA401 Demonstrates Initial Anti - Tumor Activity in Multiple Tumor Types 44 * Patients in this analysis are part of the efficacy analysis set with at least one post - treatment tumor assessment and had received IMA401 infusions at ≥1 mg and showed MAGEA4/8 target expression higher than the MAGEA4/8 qPCR threshold (n=17); Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with at least two available post infusion scans or patients with progressive disease (PD) at any prior timepoint; two patients not included in tumor shrinkage calculation or shown in the figures as they had clinical progression and post - treatment tumor assessment is not available; PR: Partial Response; cPR: Confirmed Partial Response; SD: Stable Disease 11 12 13 14 - 1 0 0 - 5 0 0 50 1 0 0 Change in Sum of Longest Diameter of Target Lesions from Baseline [%] ⯈ BL PR PD ⯈ ⯈ ⯈ ⯈ ⯈ Target Lesion r e s e c t e d ⯈ ⯈ Exploratory Analysis in Patients with MAGEA4/8 high Expression at Relevant IMA401 Doses (DL6 - 7; N=17*) ORR 29% (5/17) cO R R 25% (4/16) D CR 53% (9/17) Tumor s h rin k a g e 53% (8/15) 0 1 2 3 4 5 6 7 8 9 10 Months post First IMA401 Infusion Cancer Indications: Cut.: Cutaneous; HNSCC: Head & Neck Squamous Cell Carcinoma; LCNEC: Large Cell Neuroendocrine Carcinoma; Muc.: Mucosal; NET CUP: Neurodendocrine Tumor, Cancer of Unknown Primary; SCLC: Small Cell Lung Cancer; sqNSCLC: Squamous Cell Non - small Cell Lung Cancer; TNBC: Triple Negative Breast Cancer. BOR (RECIST 1.1) Ongoing treatment Cancer indications Beyond PRAME: IMA401 Data cut - off Jul 23, 2024 ESMO 2024

 

 

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Potential of PRAME Therapies in Solid Cancers 46 Hukelmann et al., SITC 2022, updated prevalences as of May 2025 1 Data on file: PRAME target prevalence is based on a proprietary mass spec - guided expression threshold applied to TCGA or in - house (SCLC) RNAseq data (approximate values, values between 95 - 100% shown as 95%); 2 PRAME target Immatics’ current MS - guided mRNA threshold for patient selection Selected indications Clinical activity shown No clinical activity expected PRAME Target Expression and Prevalences in Selected Solid Cancer Types Potential opportunity to see clinical activity PRAME prevalence in uveal melanoma based on IMADetect® qPCR testing of screening biopsies from clinical trial patients demonstrates substantial higher prevalence of ~90% compared to prevalence based on TCGA data of 50%, TCGA: early & late - stage primary tumor samples, Immatics clinical trials: late - stage/metastatic tumor samples, Role of PRAME in metastasis of uveal melanoma: Field et al. 2016 Clinical Cancer Research; MS: mass spectrometry 95% Cutaneous Melanoma 90% (50% 2 ) Uveal Melanoma 2 95% Uterine Carcinoma 85% Ovarian Carcinoma (serous) 95% Uterine Carcinosarcoma 95% Synovial Sarcoma 70% Squamous Cell NSCLC 65% Triple - negative Breast Carcinoma 45% Small Cell Lung Cancer 40% Kidney Carcinoma (papillary) 35% C h o l a n g ioc a r cin o m a 25% Adenocarcinoma NSCLC 25% Breast Carcinoma (all subtypes) 25% Head & Neck Squamous Cell Carcinoma 25% Esophageal Carcinoma (all subtypes) 20% Hepatocellular Carcinoma 20% Bladder Carcinoma PRAME positive patients 1

 

 

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 Progression Free Survival Data cut - off Apr 07, 2025 47 Overall Survival mPFS N 2.6 months 11 Dose Escalation 6.1 months 33 Dose Expansion mOS N 6.3 months 11 Dose Escalation 15.9 months 33 Dose Expansion • 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) PRAME Wave #1: IMA203