- CDR404 represents a potential paradigm shift in the development of T-cell engagers for solid cancers
- Epithelial cancer indications eligible for CDR404 Phase 1 trial include non-small cell lung carcinoma (NSCLC), head & neck squamous cell carcinoma and bladder cancer
ZÜRICH, Switzerland, Oct. 23, 2023presented findings on tumor target expression and precise patient selection for the upcoming Phase 1 trial of CDR404 (Abstract 200P), a first-of-its-kind bispecific and bivalent antibody fragment-based T-cell engager (TCE) targeting MAGE-A4, an intracellular protein which is presented on HLA-A*02:01 on the surface of cancer cells, at the ESMO Congress 2023, occurring October 20-24 in Madrid, Spain.
The key objective of this study was for CDR-Life to explore MAGE-A4 expression levels in solid tumors using The Cancer Genome Atlas (TCGA) mRNA dataset.
TCGA bioinformatic analyses revealed that squamous cell cancers were enriched for high levels of MAGE-A4 mRNA expression including squamous NSCLC, head and neck carcinoma associated with absence of human papillomavirus (HPV) infection, and bladder cancer. In addition, subgroups of high MAGE-A4 expression were present across a wide range of solid cancers including lung adenocarcinoma, ovarian and gastric cancers. In lung adenocarcinoma, the study has also shown preliminary evidence for a potentially discrete molecular sub-group of high MAGE-A4 tumors which might benefit from CDR404 treatment.
"CDR404 is a novel, bispecific and bivalent T-cell engager differentiated from previous solid tumor T-cell engagers targeting MAGE-A4 in the clinic. This study demonstrates that there are subgroups of high MAGE-A4 expression present across a wide range of solid cancers," said Emiliano Calvo, M.D., Ph.D., Director of START Madrid, Spain and Senior Investigator for the Phase 1 trial. "Since HLA-A*02:01 is the most prevalent HLA allele across the USA and Europe, this indicates the potential for multiple future therapeutic opportunities for CDR404 especially in patients with MAGE-A4+ tumors who cannot be effectively treated with immune checkpoint blockades."
Key takeaways:
- High levels of MAGE-A4 expression are present in different-sized sub-groups across a wide range of solid cancers with high unmet medical needs including NSCLC (squamous and adenocarcinoma histology), head and neck squamous cell carcinoma, gynecological and bladder cancers.
- The MAGE-A4 mRNA distribution profiles across multiple tumor types indicate, that a tumor MAGE-A4 assay will be indispensable for trial screening. CDR-Life has identified a highly specific MAGE-A4 immunohistochemistry (IHC) antibody for this purpose.
- Time to detection of efficacy signals in the Phase 1 trial can be optimized by prioritizing recruitment of patients with tumor types that have high median MAGE-A4 expression such as squamous lung, head and neck and bladder cancers.
"The tumor and patient selection findings presented at ESMO mark an important milestone in the development of CDR404 as a potential off-the-shelf precision immunotherapy for solid tumors," said Swethajit Biswas, M.D., Ph.D., Chief Medical Officer at CDR-Life. "We look forward to the continued progress of our innovative CDR404 T-cell engager program as we near the initiation of our Phase 1 trial, anticipated to begin in 2024."
Poster Presentation Details:
Title: Precise Tumor & Patient Selection for CDR404: A Bispecific & Bivalent MAGE-A4 T-Cell Engager
Abstract Number: 200P
Presentation Date: Saturday, October 21, 2023
Presentation Time: 1:00 p.m. CET
About CDR-Life
CDR-Life is developing highly specific antibody therapeutics to target intracellular proteins presented on the major histocompatibility complex (MHC). Our versatile MHC-targeted antibody platform increases access to a vast array of antigens that were not previously addressable, to develop a pipeline of first-in-class therapeutics across a broad range of solid tumors. With a team of proven drug development experts and backed by leading cross-Atlantic investors, we are working to redirect and activate the patient's own immune system to eliminate their tumors.
