CDR-Life has announced new developments to its programme of antibody-based T cell engagers (TCE) targeting intracellular tumour antigens MAGE-A4 and PRAME via the major histocompatibility complex.

The first patient has been dosed with CDR404, a novel, bispecific and bivalent antibody fragment-based TCE targeting MAGE-A4.

MAGE-A4 is an intracellular cancer-specific protein that is cleaved into smaller peptide fragments and presented on HLA-A*02:01 molecules at the surface of cancer cells.

The Phase I study is enrolling HLA-A *02:01+ patients with MAGE-A4+ solid cancers in the US and Europe, including squamous cell carcinomas in which MAGE-A4 is highly enriched.

CDR-Life also announced the identification and characterisation of an antibody fragment-based TCE targeting PRAME called CDR813 in a poster presentation at the 2024 European Society for Medical Oncology (ESMO) Congress.

Preferentially Expressed Antigen in Melanoma (PRAME) is a tumour-specific therapeutic target that is expressed in a range of solid tumours including lung, ovarian, melanoma, and endometrial cancers, while exhibiting only minimal expression in healthy tissues.

This TCE binds potently and bivalently to an HLA-A*02-restricted PRAME peptide on the surface of cancer cells. Pre-clinical studies have shown that CDR813 has very favourable pharmacological and manufacturability properties with best-in-class potential for the clinic.

Swethajit Biswas, Chief Medical Officer of CDR-Life, commented: “This current suite of T cell engagers targeting cancer-specific peptides presented on HLA underscores our ambitions in solid tumour oncology to create an innovative pipeline of highly specific and potent antibody fragment-based molecules targeting a wide range of cancer-specific antigens including challenging cell surface resident proteins, which are known to be directly involved in tumour growth.”

Diana Spencer, Senior Digital Content Editor, DDW