EM33

EM33 is a conditionally activated prodrug T-cell engager (ProTCE) developed by Elpiscience Biopharmaceuticals for the treatment of solid tumors. Utilizing a modular ProTCE platform, EM33 is designed to overcome the systemic toxicities and cytokine release syndrome (CRS) often associated with traditional T-cell engagers. The molecule targets a tumor-associated antigen (TAA) that is highly expressed on various solid tumors but has low expression on normal tissues. To enhance safety, EM33 employs a dual-masking strategy where both the TAA-binding and CD3-binding domains are shielded by masking peptides. These masks are connected to the antibody via a proprietary peptide linker that is specifically recognized and cleaved by multiple tumor-associated proteases. In its prodrug form, EM33 remains inactive in systemic circulation; however, upon reaching the tumor microenvironment, the linker is cleaved, restoring the molecule's full activity. Preclinical data presented at the AACR 2026 meeting demonstrated that EM33 provides a 1000-fold therapeutic window, significant tumor growth inhibition in xenograft models, and a markedly improved safety profile with minimal cytokine release compared to unmasked variants.