Immatics Announces Updated Phase 1b Clinical Data on ACTengine IMA203 TCR-T Targeting PRAME in Melanoma Patients and Provides Update on Upcoming SUPRAME Phase 3 Trial Company to host conference call and web

Updated Phase 1b Clinical Data on

ACTengine IMA203 TCR-T Targeting PRAME in Melanoma Patients and

Provides Update on Upcoming SUPRAME Phase 3 Trial

to host conference call and webcast today, October 10, at 9:00 am EDT/3:00 pm CEST

Texas and Tuebingen, Germany, October 10, 2024 - Immatics N.V.

(NASDAQ: IMTX, "Immatics" or the "Company"), a clinical-stage biopharmaceutical

company active in the discovery and development of T cell-redirecting cancer immunotherapies, today announced updated Phase 1b clinical

data on ACTengine IMA203 TCR-T targeting PRAME in melanoma patients and provided an update on SUPRAME, the upcoming Phase

3 trial to evaluate IMA203 in metastatic melanoma patients.

ongoing Phase 1b trial will be presented on Friday, October 11, 2024, by Martin Wermke, M.D., during Plenary Session 1, Developmental

Immunotherapy (Cellular Immunotherapy, Vaccines, & New Checkpoints) at the Society for Melanoma Research Congress 2024. The IMA203

data slides are accessible in the Events & Presentations' section of the Investor

& Media section of the Company's website. The conference presentation will include additional patient cases.

significant tumor shrinkage and durable responses combined with meaningful progression-free survival and overall survival outcomes after

a single treatment with ACTengine IMA203 in this patient population that have all exhausted multiple lines of systemic

treatments illustrates the impact IMA203 can have on metastatic melanoma patients," said Martin Wermke, M.D., Coordinating Investigator

of the ACTengine IMA203 TCR-T trial. "These results now affirm the therapeutic potential of IMA203 and provide

a strong rationale for the expedited late-stage clinical development of this product candidate."

"We are enthusiastic

about the clinical data as they confirm our conviction in the durability and long-term efficacy of ACTengine IMA203,

demonstrated by the favorable median progression-free survival for patients in the dose expansion cohort. I would like to highlight that

a subgroup of 12 out of 26 patients showed more than 50% reduction of tumor lesions and a median PFS of 13.4 months," said Cedrik

Britten, M.D., Chief Medical Officer at Immatics. "We believe the presentation of this data set in conjunction with our recent

meeting with the FDA, which has resulted in a pivotal trial design with progression-free survival as the primary endpoint for full approval,

positions us to advance the development of IMA203 in the second-line or later metastatic melanoma setting."

and Clinical Data Summary - ACTengine IMA203 Monotherapy Phase 1b Trial

Heavily pretreated metastatic melanoma patients

2024, 28 heavily pretreated patients with metastatic melanoma were treated at the recommended Phase 2 dose (RP2D, 1 to 10 billion total

TCR-T cells) with IMA203 during the Phase 1b dose expansion part of the clinical trial. The treated patient population is composed of

patients with a median of 2 lines of prior systemic treatments, consisting of cutaneous melanoma patients (N=13), uveal melanoma patients

(N=12), mucosal melanoma patients (N=2) and a patient with melanoma of unknown primary (N=1).

tolerability profile demonstrated across all dose levels in Phase 1a and Phase 1b

has maintained a favorable tolerability profile with no treatment-related Grade 5 adverse events in the safety population (N=701

Phase 1a and Phase 1b patients across all dose levels and all tumor types), even at doses up to ~10x109 TCR-T cells.

adverse events were expected cytopenias (Grade 1 - 4) associated with lymphodepletion as well as mostly mild to moderate cytokine

release syndrome (CRS). Some patients infrequently experienced ICANS (Grade 1: 6%, Grade 2: 4%, Grade 3: 4%).

monotherapy tolerability profile is also generally consistent with that observed in the Phase 1b melanoma subset.

and durability: Durable objective responses in melanoma patients at RP2D3

adds substantial maturity to the most recent data update from May 2024 (data cut-off on April 25, 2024). The median follow-up for the

median duration of response for this analysis was 9.3 months compared to 3.5 months in May 2024.

patients who started lymphodepletion. Includes one patient who started lymphodepletion but did not receive IMA203 TCR-T cells and one

patient who started lymphodepletion with T cell infusion scheduled after data-cut.

survival (PFS) and overall survival (OS): Significant shift in PFS and OS between Phase 1a dose escalation to Phase 1b dose expansion

in melanoma patients

Manufacturing improvements

were implemented prior to the Phase 1b part of the trial to enhance key features of IMA203. As a result, all patients in dose expansion

were treated with an updated version of IMA203 that includes a T cell enrichment process using monocyte depletion (negative selection)

or CD8/CD4 positive selection.

today demonstrate a significant positive shift in median PFS and median OS between melanoma patients treated during Phase 1a and patients

treated in Phase 1b.

tumor assessment post infusion pending for additional two melanoma patients at data-cut.

efficacy population excludes 5 patients treated at DL4 in Phase 1a of the trial as reported in the May 2024 update, based on different

manufacturing version used that affects the T cell product. See the IMA203 data presentation slides available on the Immatics website

for more detailed information and a patient population flow chart.

In addition, approximately

half of all patients in the Phase 1b trial have a deep response (>50% tumor reduction). This subgroup of patients was observed to

have a median PFS of more than one year, while patients with <50% tumor reduction (including patients with tumor size increase) were

still observed with a more than 2 times longer median PFS compared to patients treated in dose escalation with suboptimal doses.

data: IMA203 T cell dose and T cell exposure are associated with clinical responses

from patients across Phase 1a and Phase 1b indicate that IMA203 T cells rapidly engrafted in all patients after a single dose and show

a persistence of more than two years. Three associations/correlations were observed demonstrating high consistency of dose exposure,

biological data and clinical outcome in all patients treated with IMA203 for which samples were available (N=65):

Path and Manufacturing for ACTengine IMA203 Monotherapy

2024, Immatics completed a Type D meeting with the U.S. Food and Drug Administration (FDA) to confirm RP2D and the CMC package as well

as discuss the trial design for SUPRAME, the planned registration-enabling Phase 3 randomized-controlled clinical trial for IMA203. Written

post-meeting minutes from the FDA have been received.

will evaluate IMA203 targeting PRAME in 360 HLA-A*02:01-positive patients with second-line or later (2L+) unresectable or metastatic

melanoma who have received prior treatment with a checkpoint inhibitor. Patients will be randomized 1:1 for IMA203 or investigator's

choice of selected approved treatments in the 2L+ setting.

Based on the Company's

discussions with the FDA, the primary endpoint for full approval will be median PFS. Given the expected PFS of 2-3 months4 in this patient

population, as well as the PFS of 6 months observed in the data from the IMA203 Phase 1b trial, the Company has determined that utilizing

median PFS as the primary endpoint is the fastest pathway to seeking full approval and presents a more attractive commercial positioning

4 See the IMA203 data presentation

slides available on the Immatics website for more detailed information and an overview of studies.

compared to objective

response rate (ORR). Secondary endpoints for the trial will include ORR, safety, duration of response, no overall survival detriment

and patient-reported outcomes. A pre-specified interim analysis is planned for early 2026.

3 trial is planned to run globally with sites in the United States and Europe with the initial goal of seeking Biologics License Application

(BLA) approval in the United States. On October 2, 2024, Immatics also completed a meeting with the Paul Ehrlich Institute (PEI), the

German regulatory authority, and determined the same trial design for conducting the clinical trial in Germany.

is on track to commence in December 2024 and patient enrollment is forecasted to be completed in 2026. The Company aims to submit a BLA

in early 2027 for full approval.

late-stage clinical cell therapy development is supported by its differentiated manufacturing related to timeline, capabilities and facilities.

ACTengine IMA203 cell therapy products are manufactured within 7 days, followed by a 7-day QC release testing at a success

rate of >95% to reach the target dose. The Company has also completed construction of a ~100,000 square foot R&D and GMP manufacturing

facility with a modular design for efficient and cost-effective scalability intended to serve early-stage and registration-enabling trials,

as well as commercial supply. The new site is expected to start GMP manufacturing of cell therapy products in early 2025. Meanwhile,

the existing GMP facility, which is run in collaboration with UT Health, will remain active until YE 2025

a conference call and webcast today, October 10, 2024, at 9:00 am EDT/3:00 pm CEST

to discuss the clinical data.

webcast will be made available shortly after the conclusion of the call and archived on the Immatics website for at least 90 days.

IMA203 and Target PRAME

IMA203 is Immatics' most advanced TCR-based autologous cell therapy that is directed against an HLA-A*02-presented (human

leukocyte antigen) peptide derived from preferentially expressed antigen in melanoma (PRAME), a protein frequently expressed in a large

variety of solid cancers. PRAME is homogeneously and specifically expressed in tumor tissue and Immatics' PRAME peptide is present

at a high copy number per tumor cell. The peptide has been identified and characterized by Immatics' proprietary mass spectrometry-based

target discovery platform, XPRESIDENT . Through its proprietary TCR discovery and engineering platform