Immatics Presents Preclinical Proof-of-Concept Data for TCR Bispecifics Program IMA401 Targeting MAGEA4/8
- Category: Antibodies
- Published on Thursday, 29 October 2020 13:35
- Hits: 1014
- Immatics’ first TCR Bispecific program IMA401 delivers preclinical proof-of-concept demonstrating complete remissions of transplanted human tumors in mice and favorable CMC characteristics
- The IMA401 target, an HLA-A*02-bound peptide derived both from MAGEA4 and MAGEA8, shows >5-fold higher target peptide levels on cancer cells than a commonly used target peptide derived from MAGEA4
- Immatics continues to anticipate submission of an IND application for IMA401 by the end of 2021
TUEBINGEN, Germany and HOUSTON, TX, USA I October 29, 2020 I 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 a preclinical data update on IMA401, its lead T cell receptor (TCR) Bispecifics Program. IMA401 is the first product candidate from Immatics’ TCR Bispecifics pipeline, called TCER™ (T Cell Engaging Receptor), and directed against the cancer target MAGEA4/8. Immatics demonstrated specific targeting and T cell recruitment to target-positive tumors by its proprietary TCR Bispecific molecule, leading to complete remissions of human-derived tumors in xenograft mouse models. The data will be presented at the digital European Antibody Congress 2020 on November 2.
Preclinical data highlights:
- IMA401 TCER™ targets a peptide derived from the melanoma-associated antigen 4 or 8 (“MAGEA4/8”); the target peptide is highly prevalent in several solid tumor types including squamous non-small-cell lung carcinoma (sq NSCLC), head and neck squamous cell carcinoma (HNSCC) bladder, uterine, esophageal and ovarian carcinomas, as well as melanoma, sarcoma subtypes and other solid cancer types
- IMA401 TCER™ can kill tumor cells in vitro with MAGEA4/8 peptide levels similar to levels found in cancer patients
- IMA401 TCER™ shows a minimum of 1,000-fold therapeutic window between normal tissue cell reactivity and tumor cell reactivity in vitro
- IMA401 TCER™ demonstrates consistent tumor regression including complete responses in two tumor xenograft mouse studies (including patient-derived PDX models) treated once weekly at low doses
- IMA401 TCER™ molecule shows favorable pharmacokinetics with terminal half-life of 10-11 days in mice and positive purity and stability characteristics with high production yields
- IMA401 TCER™ targets an HLA-A*02-bound peptide, which is derived from two different cancer-associated proteins, MAGEA4 and MAGEA8 and shows a >5-fold higher peptide copy number per tumor cell than a commonly used MAGEA4 target peptide based on quantitative mass spectrometry data generated by Immatics´ XPRESIDENT® platform
Carsten Reinhardt, MD, PhD, Chief Development Officer at Immatics, commented: “We continue to be enthusiastic about our first TCR Bispecific candidate and the preclinical proof-of-concept data we have generated. We look forward to advancing this novel treatment modality towards clinical development. This represents a new therapeutic opportunity in addition to our adoptive cell therapy programs for cancer patients at different disease stages and with different types of solid tumors.”
For the IMA401 TCER™ program, Immatics is continuing the manufacturing development and the generation of the IND-enabling data package. Immatics expects to submit an Investigational New Drug (IND) application to the US Food and Drug Administration (FDA) or the European Authorities for the IMA401 program by the end of 2021.
The full presentation will be available on Monday, November 2, 3:20pm CET on Immatics’ website using this link.
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 manufacturability.
Immatics combines the discovery of true targets for cancer immunotherapies with the development of the right T cell receptors with the goal of enabling a robust and specific T cell response against these targets. This deep know-how is the foundation for our pipeline of Adoptive Cell Therapies and TCR Bispecifics as well as our partnerships with global leaders in the pharmaceutical industry. We are committed to delivering the power of T cells and to unlocking new avenues for patients in their fight against cancer.