On November 12, 2025 Immatics N.V. (NASDAQ: IMTX, "Immatics" or the "Company"), a clinical-stage biopharmaceutical company and the global leader in precision targeting of PRAME, reported updated Phase 1a dose escalation data from both product candidates in its TCR Bispecifics (TCER) pipeline, IMA402 PRAME Bispecific and IMA401 MAGEA4/8 Bispecific, as well as next steps for clinical development.
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"Our off-the-shelf TCR Bispecifics have a proprietary next-generation format with half-life extension that is designed to combine optimized tolerability and potent anti-tumor activity while supporting patient-convenient dosing," said Carsten Reinhardt, M.D., Ph.D., Chief Development Officer at Immatics. "We have now achieved clinical proof-of-concept for both product candidates and seen their potential to make a meaningful impact on patients with limited treatment options through deep and durable responses. We look forward to continuing to drive the development of our bispecifics to advance accessible, innovative therapies that can reach more patients and make a lasting difference in cancer care."
"Today marks the beginning of a new phase for Immatics, expanding our reach beyond cell therapy and establishing a leading position in the TCR Bispecifics field, with a clear commitment to advancing the clinical development of our bispecifics pipeline," said Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics. "Building on these data, we are excited to evaluate our IMA402 PRAME Bispecific now across multiple targeted cancer patient populations with significant unmet treatment needs and in potentially synergistic combinations. We are especially enthusiastic about the potential for profound benefit by combining IMA402 with IMA401, our MAGEA4/8 Bispecific, in patients with squamous non-small cell lung cancer, a large, highly underserved and difficult-to-treat indication."
Carsten Reinhardt, M.D., Ph.D., and Harpreet Singh, Ph.D., will present the complete TCR Bispecifics dataset and next development steps during a conference call and webcast today, November 12, at 8:30 am EST/2:30 pm CET. The presentation is accessible on the ‘Events & Presentations’ page on the Investors & Media section of the Company’s website.
IMA402 PRAME Bispecific Phase 1a Dose Escalation Data Summary
Patient Population: Advanced metastatic solid tumors with no available treatment options
As of the data cutoff on September 26, 2025, 80 heavily pre-treated patients (median of three prior systemic treatments) with recurrent and/or refractory solid tumors1 were treated with escalating dose levels of IMA402 monotherapy ranging from 0.02 mg to 30 mg. The safety population includes all 80 patients treated with IMA402. 29 patients received doses in the recommended Phase 2 dose (RP2D range) (10 to 30 mg) and, thereof, 20 patients were efficacy-evaluable2, including 14 patients with melanoma (12 cutaneous, 1 uveal, 1 unknown primary), 3 patients with ovarian carcinoma and 3 patients with other solid cancers3.
Safety: Treatment with IMA402 showed favorable tolerability
IMA402 showed favorable tolerability across a wide dose range in the 80 patients treated. The most frequent treatment-related adverse events (AEs) were expected and transient lymphopenia, consistent with the mechanism of action, and low-grade cytokine release syndrome (CRS): Grade 1: 33%, Grade 2: 5%, Grade 3: 0%, Grade 4: 1%. No ICANS or IMA402-related Grade 5 events occurred. Tolerability across all doses was consistent with tolerability at the RP2D range.
Phase 1a dose escalation in the monotherapy setting has been completed. The maximum tolerated dose (MTD) has not been reached. The provisional RP2D range has been identified at 10 to 30 mg. The Phase 1b dose expansion is ongoing at two distinct doses within the RP2D range, and the evaluation of IMA402 in combination with an immune checkpoint inhibitor has been initiated.
Anti-tumor Activity and Durability: Deep and durable responses observed at RP2D range
IMA402 showed a clear dose-response relationship across three different dose groups.
Deep and durable responses at RP2D range (RECIST 1.1)
All
Indications Melanoma Ovarian
Carcinoma
cORR 30% (6/20) 29% (4/14) 2/3
mDOR,
mFU month Not reached
4.2 Not reached
7.3 Not reached
2.2
Tumor shrinkage 55% (11/20) 57% (8/14) 2/3
DCR (at week 6) 65% (13/20) 71% (10/14) 2/3
mDOR: median duration of response; mFU: median follow-up; DCR: disease control rate
For patients across all indications treated within the RP2D range early, promising progression-free survival (PFS) and overall survival (OS) were observed:
Median PFS was 4.8 months at a mFU of 6.8 months; 6-month PFS rate was 45%
Median iPFS4 was not reached at a mFU of 6.3 months; 6-month iPFS rate was 58%
Median OS was not reached at a mFU of 5.4 months; 1-year OS rate was 94%
Clinical Development Opportunities for IMA402 PRAME Bispecific
Based on the promising Phase 1a dose escalation data, Immatics is advancing its IMA402 PRAME Bispecific into Phase 1b dose expansion at two distinct doses to determine the final RP2D, both as a monotherapy and in combination with an immune checkpoint inhibitor with a focus on melanoma and gynecologic cancers in 2026. Depending on the outcomes of these Phase 1b cohorts, the Company would seek to convert existing Phase 1b cohorts into Phase 2 trials, which will then have the potential to become registration-directed. As part of its strategy to maximize the IMA402 opportunity, the Company is also exploring the option to initiate additional Phase 1b cohorts in 2026 to determine the monotherapy and combination potential of IMA402 with immune checkpoint inhibitors and standard of care in late as well as earlier treatment lines. As an additional opportunity, the Company is exploring the potential combination of IMA402 with IMA401 MAGEA4/8 in squamous non-small cell lung cancer (sqNSCLC) and potentially other solid tumor indications.
IMA401 MAGEA4/8 Bispecific Phase 1a Data Summary
Patient Population: Heavily pre-treated patients with a broad range of tumor types with no available treatment options
As of the data cutoff on September 26, 2025, 55 heavily pretreated patients (median of four prior systemic treatments) with recurrent and/or refractory solid tumors5 were treated with escalating dose levels of IMA401 ranging from 0.0066 mg to 2.5 mg with or without an immune checkpoint inhibitor (ICI, pembrolizumab). The safety population includes all 55 patients treated with IMA401 as a monotherapy (n=46) or in combination with pembrolizumab (n=9). 44 patients were treated with doses from 1 to 2.5 mg, and thereof 38 were evaluable for efficacy6. All efficacy-evaluable patients treated with IMA401 in combination with pembrolizumab (n=4) had progressed on prior immune checkpoint inhibitor treatments.
Safety: Treatment with IMA401 showed favorable tolerability at RP2D
The most frequent and relevant treatment-related adverse events (AEs) across all 55 patients treated with IMA401 were low-grade cytokine release syndrome (CRS) (24% G1, 11% G2, no ≥ Grade 3), mostly at the first step dose, expected and transient lymphopenia, consistent with the mechanism of action, as well as neutropenia, which was mostly transient, not re-occurring after resolution under continued treatment and well-manageable at the RP2D range of 1-2 mg. Notably, no ICANS was observed. The tolerability of IMA401 in combination with pembrolizumab is consistent with the tolerability of IMA401 monotherapy.
The maximum tolerated dose (MTD) has not been reached; three dose-limiting events were observed at 2.5 mg. The Phase 1a dose escalation has been completed, and the provisional RP2D range has been identified at 1-2 mg. At RP2D, the tolerability profile was favorable.
Anti-tumor Activity and Durability: Promising clinical activity and deep and durable responses were observed in patients with head and neck cancer, melanoma and lung cancer treated at ≥1 mg
Patients in three focus indications treated with ≥1 mg of IMA401 as a monotherapy or in combination with pembrolizumab demonstrated clinical activity:
Head and neck cancer: cORR of 25% (2/8), disease control rate of 63% (5/8)
Melanoma: cORR of 29% (2/7), disease control rate of 57% (4/7)
Squamous non-small-cell lung cancer: 1 partial response at first scan for a heavily pre-treated, ICI-resistant patient, 1 patient with stable disease for >4 months and overall survival of approximately 16 months, 1 patient with progressive disease with shrinkage of liver target lesions
The duration of all confirmed responses was longer than 6 months post treatment, with the longest response ongoing over 2 years in a patient with advanced cutaneous melanoma.
Clinical Development Opportunity for IMA401 MAGEA4/8 Bispecific
Consistent with Immatics’ focus on advancing its PRAME franchise, the Company is exploring IMA401 in combination with IMA402, starting with squamous non-small cell lung cancer (sqNSCLC). Based on the clinical proof-of-concept of both bispecific candidates, including the initial promising activity of IMA401 in head and neck cancer and sqNSCLC, as well as preclinical proof-of-concept data, Immatics is well-positioned to assess the synergistic potential of combining two different bispecifics, IMA402 targeting PRAME and IMA401 targeting MAGEA4/8, with and without a checkpoint inhibitor. As over 90% of patients with sqNSCLC are positive for PRAME and/or MAGEA4/8, a potential IMA402 and IMA401 combination treatment could provide broad treatment coverage for this patient population. Approximately 60% of patients with sqNSCLC are positive for both targets, which could boost anti-tumor activity and counteract potential tumor escape mechanisms. The current addressable patient population for metastatic sqNSCLC in the United States and EU5 includes an estimated 40,000 patients per year.
(Press release, Immatics, NOV 12, 2025, View Source [SID1234659819])