We already talked about CLSP-1025, a first-in-class T-cell engager (TCE) designed to target the p53^R175Hmutant protein, a mutation commonly found in solid tumors such as colorectal, esophageal, gastric, gynecological, lung, pancreatic, and prostate cancers.

The development of CLSP-1025 involves the use of TCEs engineered to selectively target cancer cells without affecting healthy tissues. This specificity is achieved by focusing on shared cancer neoantigens, derived from oncogenic driver mutations and presented on cancer cells by human leukocyte antigen (HLA). A proprietary platform mimicking the natural immune synapse facilitates the bridging of cancer cells and T cells through CD3 binding, leading to T-cell activation and the destruction of cancer cells.

In preclinical studies, CLSP-1025 demonstrated high selectivity for the p53^R175H mutant peptide presented on HLA-A02:01, with no observed reactivity toward wildtype p53 or other human peptides. Effective activation of T cells and the killing of patient-derived organoids at endogenous target expression levels were observed. In vivo studies further showed tumor regression in established models, highlighting the therapy’s precision and efficacy.

This milestone would mark the entry of the first TCE targeting a shared cancer neoantigen into clinical evaluation. The therapy is envisioned as a novel approach to immunotherapy, potentially addressing cancers with significant unmet needs.

Clinical trial.