On 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, reported 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 (Press release, Immatics, MAY 11, 2021, View Source [SID1234579679]). 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.
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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.
Carsten Reinhardt, M.D., Ph.D., Chief Development Officer at Immatics commented: "Having generated a strong preclinical proof-of-concept data package for our second TCR Bispecifics program is a significant milestone for Immatics. Together with our Adoptive Cell Therapy (ACT) program IMA203, which also targets PRAME, we are attacking this ubiquitous cancer cell protein from two different angles using our distinct therapeutic modalities. Based on the demonstrated preclinical data supporting significant single-agent activity of both of our TCER programs against established tumors, we are looking forward to advancing our TCER candidates, IMA401 and IMA402, into the clinic with the aim to treat cancer patients who have an urgent need for new treatment options."
For the IMA402 TCER program, Immatics has initiated GMP process development activities to advance this program towards the Investigational New Drug (IND) stage and clinical development. The company’s first TCER program, IMA401 remains on track for submission of a clinical trial application (CTA) by year end 2021. The company had previously announced preclinical proof-of-concept data for IMA401 in last quarter of 2020.
The full presentation of preclinical data from the IMA402 program is available on Immatics’ website using this link.
About TCER
Immatics’ TCER molecules are antibody-like "off-the-shelf" biologics that leverage the body’s immune system by redirecting and activating T cells towards cancer cells expressing a specific tumor target. To do so, the proprietary biologics are engineered to have two binding regions. The first region contains an affinity- and stability-improved TCR that binds specifically to the cancer target on the cell surface presented by a human leukocyte antigen (HLA) molecule. The second region is derived from an antibody domain that recruits endogenous T cells to the tumor to become activated. The design of the TCER molecules enables the activation of any T cell in the body to attack the tumor, regardless of the T cells’ intrinsic specificity. In addition, the TCER molecule has a Fc-part conferring stability, half-life extension and enhanced manufacturability.