"Immatics Presents Preclinical Proof-of-Concept Data for TCR Bispecifics Program IMA402 Targeting PRAME
May 11, 2021
Immatics’ second TCR Bispecifics program IMA402 demonstrates tumor cell killing in vitro and complete regressions of established tumors in an in vivo tumor model
IMA402 targets an Immatics-validated peptide derived from PRAME, one of the most frequently expressed intracellular cancer targets for TCR therapy
Immatics has selected a clinical lead candidate for the IMA402 program and initiated manufacturing activities
Tuebingen, Germany and Houston, Texas, May 11, 2021 – Immatics N.V. (NASDAQ: IMTX, “Immatics”), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, today announced data from its second T cell receptor (TCR) Bispecifics program, IMA402, supporting preclinical proof-of-concept for the program and further validating this proprietary therapeutic modality. IMA402 is directed against the cancer target PRAME, a protein that is frequently expressed in many solid cancers, thereby supporting the program’s potential to address a broad cancer patient population. IMA402 is the second program originating from Immatics’ TCR Bispecifics pipeline, called TCER® (T Cell Engaging Receptor). The lead candidate showed anti-tumor activity against PRAME-positive cancer cells leading to consistent reduction of the engrafted tumors, including complete responses in an in vivo mouse model. The preclinical data will be presented at the virtual 17th Annual PEGS Boston Protein Engineering and Cell Therapy Summit, on May 11-13, 2021.
Preclinical data highlights:
The IMA402 TCER® candidate targets an HLA-A*02-bound peptide derived from preferentially expressed antigen in melanoma (PRAME).
The target peptide was selected and validated based on quantitative mass spectrometry data from Immatics’ proprietary XPRESIDENT® platform and is prevalent in many solid tumor indications including lung, ovarian and breast cancer as well as other solid cancer types.
Over 50 different human wild-type TCRs recognizing the PRAME target peptide were systematically evaluated using Immatics’ XCEPTOR® platform. Two TCRs with high avidity and specificity were selected and affinity-enhanced by at least 1,000-fold while retaining specificity through the XPRESIDENT®-guided screening for off-target toxicity and cross-reactivity. Different engineered TCR variants were then incorporated into the bispecific TCER® scaffold and the best candidate was selected.
The IMA402 TCER® candidate induces killing of tumor cells in vitro with PRAME target peptide levels similar to levels found in cancer patients.
Administration of IMA402 TCER® candidate leads to consistent tumor regression including complete responses in an in vivo mouse model.
The IMA402 TCER® candidate demonstrates selective PRAME recognition leading to an at least 1,000-fold therapeutic window between tumor and normal cell reactivity in vitro.
Preclinical data support antibody-like profiles for manufacturability and pharmacokinetics of the IMA402 TCER® candidate..."
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