Immatics N.V. announced a comprehensive preclinical data set for its T cell engaging receptor (TCER«) product candidate IMA402 at the European Society for Medical Oncology (ESMO) Congress 2022 held in Paris, France, from September 9 to 13, 2022. IMA402 is the companyÆs second program in its TCR Bispecifics pipeline and is directed against an HLA-A*02:01-presented peptide derived from PRAME, a cancer target broadly expressed in many solid tumors. The data are available as an ePoster on the ESMO platform at 9 AM on September 10, and will be presented during the poster session from noon to 1 PM CEST on September 12.

Immatics TCER« molecules are ôoff-the-shelfº TCR Bispecifics engineered with two binding regions: a TCR domain and a T cell recruiter domain. 1) Clinical Trial Application (CTA) is the equivalent of an Investigational New Drug (IND) application in Europe. Data Highlights: TCER« format is optimized for efficacy and safety: The IMA402 TCER« utilizes a high-affinity TCR designed to specifically bind to an HLA-A*02:01-presented peptide derived from PRAME on tumor cells, The T cell recruiter domain is a proprietary low-affinity T cell recruiter against the TCR/CD3 complex that demonstrates superior in vivo tumor control compared to analogous TCER« molecules designed with higher-affinity variants of a widely used antibody recruiter, The IMA402 TCER« is optimized to reduce T cell engager-associated toxicities in patients, which is demonstrated by reduced recruiter-mediated cytokine release in vitro; Compelling preclinical data: IMA402 showed potent and selective activity against PRAME-positive tumor cell lines in vitro, In vivo studies in mice demonstrated dose-dependent anti-tumor activity of IMA402.

Sufficiently high drug doses were key to achieving the desired anti-tumor effects over a prolonged period, In vitro safety assessment including toxicity screening against 20 normal tissue types, whole blood cytokine release assessment and alloreactivity evaluation confirmed favorable safety profile for IMA402, The half-life extended format of IMA402 confers a serum half-life of >1 week in mice suggesting a favorable dosing regimen and prolonged drug exposure at therapeutic levels when compared to TCR Bispecifics lacking half-life extension strategies; Clinical trial evaluating IMA402 in patients with solid tumors to start in 2023: IMA402 is designed to allow high dosing not limited by toxicities with the goal of reaching relevant therapeutic doses in tumor tissue and achieve a meaningful clinical benefit in patients. To enable the start of the Phase 1/2 trial in 2023, Immatics has completed the manufacturing process development for IMA402 and manufacturing of the clinical batch is on track for 2H 2022. The Phase 1 part of the trial will start with a minimal anticipated biological effect level (MABEL) dose of IMA402 and will have an adaptive design aimed at accelerating dose escalation to determine the recommended Phase 2 dose (RP2D).

HLA-A*02:01-positive patients with different solid tumors expressing PRAME will initially receive weekly infusions of IMA402. Pharmacokinetics data will be assessed throughout the trial and might provide an opportunity to adapt the treatment interval. The Phase 2a dose expansion part of the trial will be designed to comprise several cohorts to further evaluate IMA402 in specific indications and combination therapies.

Submission of the IND1 application is planned for Second Quarter 2023.