31/05/2025 - Immatics NV: IMA203 PRAME Cell Therapy Phase 1b Data in Patients with Metastatic Melanoma

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IMA203 PRAME Cell Therapy in Advanced Melanoma

- Phase 1b Dose Expansion Clinical Data Update

May 31, 2025

Data cut-off April 7, 2025

Delivering the Power of T cells to Cancer Patients

© Immatics. Not for further reproduction or distribution.



  • 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. 2Hamid O, et al. Ann Oncol. 2019;30:582-588. 3Goldinger SM, et al. Eur J Cancer. 2022;162:22-33. 4Wermke 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

Data cut-off Apr 7, 2025 2

ASCO 2025

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%

PRAME prevalence in selected indications



Precision targeting

of PRAME







≥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;

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

(…)

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

Data cut-off Apr 7, 2025 4

ASCO 2025

Patient Journey

SCREENING/MANUFACTURING

TREATMENT / OBSERVATION FU

HLA-A*02:01 Testing

Blood

Inclusion of HLA-A*02:01-

positive patients

Leukapheresis

IMA203

One-time infusion

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

PRAME Testing

Biopsy or archived tissue Inclusion of PRAME-positive patients

Lymphodepletion

Fludarabine 30mg/m2Cyclophosphamide 500mg/m2Days -6 to -3

Low Dose IL-2a

1m IU SC Days 1-5;

1m IU SC BID Days 6-10



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



Key Objectives

Primary:

  • Tolerability

  • Determination of RP2D (Phase 1a)

    Secondary:

  • IMA203 T cell engraftment, persistence

  • Efficacy



RP2D defined at

1-10x109TCR T cells

n=1 in Phase 1a

started lymphodepletion but did not receive IMA203

n=27

Phase 1a Dose Escalation

(DL1-4)

n=46

Phase 1b Dose Expansion

(RP2D)

n=13

non-melanoma

Melanoma Efficacy

Population1(n=33)

n=14

cutaneous melanoma

n=16

uveal melanoma

n=3

other melanoma2



1 Melanoma efficacy population excludes 1 patient with uveal melanoma with ongoing unconfirmed PR from cORR; 2Mucosal melanoma n=2, melanoma of unknown primary n=1;

RP2D: 1-10x109TCR T cells; DL4: 0.2-1.2x109TCR T cells/m2BSA; DL: dose level.

Data cut-off Apr 7, 2025 5

ASCO 2025

Total Safety

Population

(N=74)

Disclaimer

Immatics NV published this content on May 31, 2025, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 31, 2025 at 12:34 UTC.

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