ZURICH, Switzerland — CDR-Life, Inc., a biotechnology company developing highly selective T cell engagers to treat cancer and autoimmune diseases, has presented the first clinical data demonstrating that its lead M-gager T cell engager, CDR404, achieved all four hallmark pharmacodynamic indicators of T cell engager activity in patients with MAGE-A4 positive solid tumors. The findings, shared at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, highlight strong immune activation and early signs of clinical benefit, including tumor stabilization and biomarker improvement in patients with ovarian cancer and synovial sarcoma.
CDR404 is an antibody-based T cell engager designed to target intracellular tumor antigens presented on HLA molecules. It binds to MAGE-A4 peptides displayed by HLA-A*02:01 on tumor cells and redirects CD3 positive T cells to destroy the targeted cancer cells. The ongoing Phase 1 CDR404 trial (NCT06402201) is being conducted at major cancer centers in the United States and Europe. Unlike conventional T cell receptor-based therapies, the proprietary M-gager platform uses antibody-derived binding domains that offer strong specificity, potency, and manufacturability.
At early dose levels of 100 to 200 micrograms, CDR404 produced all four canonical pharmacodynamic effects associated with T cell engager therapy, including CD8 positive T cell activation and expansion, conversion to a memory phenotype, and recruitment of lymphocytes into tumor sites. Repeated dosing did not trigger PD-1–mediated T cell exhaustion, indicating sustained biological activity. One patient experienced a temporary tumor flare followed by stabilization, consistent with immune cell infiltration into the tumor.
“These early data demonstrate that our M-gager platform can extend the precision and power of antibody-based T cell engagers to intracellular antigens, an area long thought to be accessible only to TCR-based modalities,” said Christian Leisner, Ph.D., Chief Executive Officer of CDR-Life. “Seeing all four pharmacodynamic hallmarks of activity in patients even at low doses underscores the potential of this approach to redefine how we target solid tumors.”
The first-in-human dose was determined using quantitative systems pharmacology modeling, allowing detection of pharmacodynamic effects more efficiently than traditional methods. Based on these promising results, the trial will now focus on patients with MAGE-A4 positive ovarian cancers, a population with significant unmet medical need.
Additional analyses, including integrated pharmacokinetic-pharmacodynamic assessments and circulating tumor DNA data, are underway.
