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PSMA-XPAT is an experimental protease-activated bispecific T‑cell engager designed to target prostate-specific membrane antigen (PSMA) on tumor cells while engaging CD3 on T cells, using Amunix’s PRO-XTEN masking platform to improve the therapeutic index. It incorporates a dual-masked TCE architecture in which XTEN polypeptide “masks” linked via protease-cleavable linkers sterically block binding in systemic circulation, with unmasking and activation occurring preferentially in the protease-rich tumor microenvironment to limit off-tumor CD3 activation and cytokine release. Initially developed by Amunix (later acquired by Sanofi) for metastatic castration-resistant prostate cancer, PSMA-XPAT was classified mechanistically as a CD3 stimulant and PSMA inhibitor–type TCE; however, the program’s global R&D status has been reported as discontinued.
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