On March 27, 2025 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, reported a business update and announced financial results for the quarter and full year ended December 31, 2024 (Press release, Immatics, MAR 27, 2025, View Source [SID1234651523]).
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"2025 will be marked by milestones across our TCR-T and TCR Bispecifics clinical portfolio, including advancing two of our main objectives for this year: firstly, reporting data on solid cancer types beyond melanoma, such as ovarian cancer, head and neck cancer and others and secondly, demonstrating that our next-generation, half-life extended TCR Bispecifics can deliver meaningful response rates in advanced solid cancer patients," said Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics. "Additionally, the initiation of SUPRAME, the Phase 3 trial for our lead TCR-T cell therapy, IMA203, represents a transformative step in Immatics’ journey towards becoming a commercial-stage enterprise. We believe IMA203 offers patients and their treating physicians a cell therapy with impressive response rates and favorable tolerability in advanced melanoma. Notably, it requires no surgery or biopsy, has a fast turnaround time and a high manufacturing success rate. We are committed to rapidly delivering the first TCR therapeutic targeting PRAME to the market and to cancer patients, serving their unmet medical needs."
Full Year 2024 and Subsequent Company Progress
ACTengine Cell Therapy Programs
ACTengine IMA203 (PRAME)
IMA203 is Immatics’ lead TCR-T cell therapy, currently being evaluated in a Phase 3 trial (SUPRAME) in patients with previously treated advanced melanoma. IMA203 has the potential to become the first TCR therapeutic targeting PRAME to enter the market. In parallel, Immatics is priming its in-house, state-of-the-art TCR-T manufacturing facility to serve its planned commercial supply. In addition to maximizing the PRAME cell therapy opportunity, Immatics plans to expand IMA203 into uveal melanoma through the ongoing Phase 1b clinical trial. The current addressable patient population of PRAME/HLA-A*02:01-positive 2L unresectable or metastatic cutaneous melanoma in the US and EU52 is ~7,300 plus ~1,300 uveal melanoma patients in the US and EU5.
Clinical and commercial development plan for ACTengine IMA203 TCR-T
Based on the positive Phase 1b clinical data presented in 2024 and supported by the FDA RMAT designation3, Immatics has advanced its lead TCR-T product candidate, IMA203 targeting PRAME, into a randomized-controlled Phase 3 trial, called "SUPRAME" (NCT06743126). The trial commenced in December 2024. The first patient was randomized in the United States and enrollment continues as planned.
SUPRAME is a prospective, multicenter, open-label, randomized-controlled Phase 3 clinical trial evaluating the efficacy, safety and tolerability of IMA203 TCR-T in patients with unresectable or metastatic cutaneous melanoma who have received prior treatment with a checkpoint inhibitor. 360 HLA-A*02:01-positive patients will be randomized 1:1 to treatment with IMA203 or investigator’s choice of selected approved treatments in the 2L setting (nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (US), chemotherapy). Based on the Company’s discussions with the FDA, the primary endpoint for seeking full approval will be blinded independent central review ("BICR")-assessed (RECIST v1.1) progression-free survival (PFS). Given the expected median PFS of 2-3 months in this patient population4, as well as the median PFS of 6 months (> 1 year in patients with deep responses) observed in the data from the IMA203 Phase 1b trial, the Company has determined that utilizing PFS as the primary endpoint is the fastest pathway to seeking full approval and presents a more attractive commercial positioning as compared to objective response rate (ORR). Secondary endpoints for the trial include ORR, safety, DOR, OS and patient-reported outcomes.
The trial is planned to run internationally with approximately 50 sites in the United States and Europe.
Patient enrollment for SUPRAME is forecasted to be completed in 2026. A pre-specified interim data analysis will be triggered upon the occurrence of a defined number of events for PFS (progressive disease or death)5 anticipated to occur after approximately 200 patients are enrolled in 1Q 2026. The final analysis is planned for 4Q 2026. Immatics aims to submit a Biologics License Application (BLA) in 1Q 2027 for full approval and to launch IMA203 in 3Q 2027.
In addition to cutaneous melanoma, Immatics intends to expand the IMA203 TCR-T opportunity to treat uveal melanoma patients and will continue to evaluate IMA203 in this patient population through the ongoing Phase 1b trial.
Manufacturing capabilities
Immatics’ proprietary manufacturing process, timeline, capabilities and facility support late-stage clinical and commercial cell therapy development and supply.
IMA203 products are manufactured from a patient’s leukapheresis (with no surgery required) within 7 days, followed by 7-day QC release testing at >95% success rate6 to achieve the target dose (1-10×109 TCR-T cells). The Company’s state-of-the-art ~100,000 sq. ft. R&D and GMP manufacturing facility in the Houston Metropolitan Area was built with a modular design for efficient and cost-effective scalability (total of 8 manufacturing suites, plus further expansion space) to serve early-stage and registration-directed clinical trials as well as planned commercial supply. Through in-house manufacturing and QC testing, Immatics aims to better control the manufacturing process, shorten the turnaround time, ensure the manufacturing success rate and quality of the product and realize potential cost efficiencies, including manufacturing capacity optimization through scalability for a competitive and profitable commercial cell therapy product.
Clinical data on ACTengine IMA203 TCR-T as of October 2024
On October 10, 2024, Immatics provided a data update on IMA203 monotherapy in 28 heavily pretreated metastatic melanoma patients from the ongoing Phase 1b dose expansion part of the clinical trial in which patients were treated at the recommended Phase 2 dose (RP2D, 1 to 10 billion total TCR-T cells).
As of the data cut-off on August 23, 2024, treatment with IMA203 monotherapy in this melanoma patient population has demonstrated:
Confirmed objective response rate of 54% and an objective response rate of 62%
Disease control rate of 92% and tumor shrinkage in 88% of patients
12.1 months median duration of response, 6 months median progression-free survival and >1-year median progression-free survival in patients with deep responses
Median overall survival has not yet been reached at a median follow-up time of 8.6 months
IMA203 monotherapy has maintained a favorable tolerability profile with no treatment-related Grade 5 events in the entire safety population (N=70 Phase 1a and Phase 1b patients across all dose levels and all tumor types).
Immatics plans to present updated clinical data from the Phase 1b trial, including patients reported previously with longer follow-up and additional uveal melanoma patients, in 2025.
ACTengine IMA203CD8 TCR-T (GEN2) Monotherapy (PRAME)
IMA203CD8 is the Company’s second-generation cell therapy product candidate targeting PRAME. Given its pharmacology profile, once the target dose is reached, the Company intends to pursue the clinical development of this product in PRAME-positive solid cancers beyond melanoma, starting with gynecologic cancers.
On November 8, 2024, Immatics announced updated Phase 1 dose escalation clinical data on its next-generation ACTengine IMA203CD8 TCR-T cell therapy in 44 heavily pretreated HLA-A*02:01 and PRAME-positive patients with solid tumors, thereof 41 patients being evaluable for efficacy. Of note, these patients had been treated at substantially lower doses than IMA203 (GEN1), i.e. in a range of 0.2-0.48×109 TCR-T cells/m2 BSA (dose level 3) to 0.801-1.2×109 TCR-T cells/m2 BSA (dose level 4c) T cells infused.
As of the data cut-off on September 30, 2024, treatment with IMA203CD8 monotherapy demonstrated:
Confirmed objective responses observed in 41% of patients (at low doses, dose escalation ongoing)
Median duration of response of 9.2 months at a median follow-up of 13.1 months
Tumor shrinkage of target lesions in 84% of patients and disease control rate at week 6 of 85%
10 out of 17 responses were ongoing, of which three confirmed responses were ongoing at 14+, 15+ and 24+ months
Deep responses with ≥50% tumor size reduction were observed in 11 out of 17 responders. This group included two patients with complete response of target lesions, of which one patient showed a complete metabolic response according to a PET-CT scan
IMA203CD8 monotherapy has maintained a manageable tolerability profile in the 44 patients treated.
Based on the enhanced pharmacology of IMA203CD8 demonstrated in this trial, the evaluation of higher doses of IMA203CD8 in the ongoing dose escalation trial opens the possibility of addressing hard-to-treat solid tumor indications with both high- and medium-level PRAME copy numbers, such as ovarian cancer, uterine cancer, squamous non-small cell lung carcinoma, triple negative breast cancer and others.
The next clinical data update including dose escalation and ovarian cancer is planned in 2025.
TCR Bispecifics Programs
TCER IMA402 (PRAME)
To expand the PRAME opportunity to additional solid cancer types and earlier lines of treatment, the Company is focusing on its half-life extended TCR Bispecific, IMA402. Upon delivering clinical proof-of-concept ("PoC") in last-line melanoma, Immatics plans to explore its potential in gynecologic cancers, sqNSCLC, breast cancer and other solid tumor indications as well as earlier lines of solid cancers, such as first-line (1L) cutaneous melanoma.
On November 18, 2024, Immatics announced the first clinical data update from the ongoing Phase 1 dose escalation trial evaluating its next-generation, half-life extended TCR Bispecific molecule, TCER IMA402 targeting PRAME, in 33 heavily pretreated (3 median lines of prior therapies) HLA-A*02:01-positive patients with recurrent and/or refractory solid tumors.
As of the data cut-off on November 6, 2024, treatment with IMA402 demonstrated a favorable tolerability profile in the 33 patients treated.
Early pharmacokinetic data indicated a median half-life of approximately seven days, potentially enabling bi-weekly dosing. Initial signs of clinical anti-tumor activity have been observed and are associated with PRAME expression and IMA402 dose levels administered (up to 4 mg at DL8).
In the PRAME-negative patient population across all doses and indications, only one patient out of seven (14%) showed tumor shrinkage of -2.9%
25% (3/12) of patients (PRAME+ or not tested) treated at low doses (DL1-6) showed tumor shrinkage, including one unconfirmed partial response in cutaneous melanoma
78% (7/9) of patients (PRAME+ or not tested) treated at relevant doses (8 patients at DL7 and 1 patient at DL8) experienced shrinkage of their target lesions, including one confirmed partial response in melanoma ongoing at 3 months and three patients with ongoing stable disease at 6+ weeks (cut. melanoma), 3 months (ovarian cancer), 8+ months (uveal melanoma)
Based on the initial signs of dose-dependent and PRAME target expression-dependent clinical activity observed during dose escalation, the Company will continue to evaluate IMA402 at higher dose levels to determine the optimal therapeutic dose.
As of March 27, 2025, dose escalation remains ongoing at DL10 (8 mg) with MTD not reached.
The next update on the Phase 1a trial with clinical data at relevant dose levels in second-line and later melanoma is planned in 2025.
TCER IMA401 (MAGEA4/8)
Immatics is further harnessing the potential of its proprietary bispecific platform to develop innovative therapeutics and unlock more cancer types. The Company’s half-life extended TCR Bispecific, IMA401 targeting MAGEA4/8, is progressing through a Phase 1 trial in patients with sqNSCLC, HNSCC, bladder cancer and other solid tumor indications, with the primary goal of developing this product candidate in earlier treatment lines.
On September 16, 2024, Immatics announced the proof-of-concept clinical data for the first candidate of its next-generation, half-life extended TCR Bispecifics platform, TCER IMA401 (MAGEA4/8), during an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024.
As of data cut-off on July 23, 2024, 35 heavily pretreated patients with recurrent and/or refractory solid tumors were treated with IMA401 monotherapy across nine escalating dose levels. The treated patient population was composed of patients with 16 different solid tumor indications who were both HLA-A*02:01 and MAGEA4/8-positive, had received a median of four and up to eight lines of prior systemic treatments and the majority had an ECOG performance status of ≥ 1.
Proof-of-concept clinical data from the Phase 1a first-in-human dose escalation basket trial showed initial anti-tumor activity in multiple tumor types, durable objective responses, including confirmed responses ongoing at 13+ months, a manageable tolerability profile and a half-life of 14+ days.
Treatment with IMA401 monotherapy in patients with relevant IMA401 doses and MAGEA4/8high levels (N=17) demonstrated:
Objective response rate of 29% with confirmed responses observed in 25% of patients
Disease control rate of 53% and tumor shrinkage of 53%
As the clinical trial progresses, the Company aims to further leverage the potential of IMA401 by focusing on the enrollment of indications with high MAGEA4/8 target expression, such as lung and head and neck cancer patients, seeking to optimize the treatment schedule. By further combining IMA401 with a checkpoint inhibitor, Immatics aims to generate relevant clinical data to position IMA401 as a combination therapy in earlier treatment lines.
The next update on IMA401 Phase 1a data, with a focus on head and neck cancer, is expected in 2025, and the Company plans to share data with a focus on non-small cell lung carcinoma in 2026.
Corporate Development
IMA203 and mRNA Combination (Moderna collaboration): In February 2025, the FDA granted IND clearance for a Phase 1 trial evaluating Immatics’ IMA203 PRAME TCR-T in combination with Moderna’s PRAME adaptive immune modulating therapy. The objective of the combination is to further enhance IMA203 T cell responses with the potential to significantly reduce turn-around time and costs through the infusion of a much lower cell dose. The first-in-human, Phase 1a/1b trial is a multicenter, open-label, dose escalation/de-escalation (adaptive design) trial evaluating the safety, tolerability and efficacy of the combination therapy in up to 15 patients with advanced or recurrent cutaneous melanoma and synovial sarcoma. Immatics is responsible for conducting the Phase 1 trial. Each party retains full ownership of its investigational PRAME compound, and the parties will fund the clinical study on a cost sharing basis. In November 2024, Immatics presented preclinical proof-of-concept data at SITC (Free SITC Whitepaper) supporting this combination.
In September 2024, Immatics regained full clinical development and commercialization rights to IMA401 due to ongoing portfolio prioritization efforts within Bristol Myers Squibb. The Phase 1 trial with IMA401 is ongoing and will continue to be conducted by Immatics.
Full Year 2024 Financial Results
Cash Position: Cash and cash equivalents as well as other financial assets total $628.0 million1 (€604.5 million) as of December 31, 2024, compared to $442.5 million1 (€425.9 million) as of December 31, 2023. The increase is mainly due to the public offering in January and October 2024, partly offset by ongoing research and development activities.
Revenue: Total revenue, consisting of revenue from collaboration agreements, was $161.9 million1 (€155.8 million) for the year ended December 31, 2024, compared to $56.1 million1 (€54.0 million) for the year ended December 31, 2023. The increase is mainly the result of the one-time revenue associated with the termination of the IMA401 and ACTallo collaborations by Bristol Myers Squibb during the year ended December 31, 2024.
Research and Development Expenses: R&D expenses were $153.9 million1 (€148.1 million) for the year ended December 31, 2024, compared to $123.3 million1 (€118.7 million) for the year ended December 31, 2023. The increase mainly resulted from costs associated with the advancement of the product candidates in clinical trials.
General and Administrative Expenses: G&A expenses were $48.2 million1 (€46.4 million) for the year ended December 31, 2024, compared to $39.7 million1 (€38.2 million) for the year ended December 31, 2023.
Net Profit and Loss: Net profit was $15.8 million1 (€15.2 million) for the year ended December 31, 2024, compared to a net loss of $98.3 million1 (€94.6 million) for the year ended December 31, 2023. The net profit largely resulted from the one-time revenue from collaborations, offset by ongoing expenses.
Full financial statements can be found in our Annual Report on Form 20-F filed with the Securities and Exchange Commission (SEC) on March 27, 2025, and published on the SEC website under www.sec.gov.
Upcoming Investor Conferences
Bank of America Healthcare Conference, Las Vegas (NV) – May 13 – 15, 2025
Jefferies Global Healthcare Conference, New York (NY) – June 3 – 5, 2025
To see the full list of events and presentations, visit View Source