EGFR-XPAT

**EGFR-XPAT** is a protease-activated, masked T-cell engager (TCE) developed by Amunix Pharmaceuticals using the XPAT platform. It consists of a bispecific TCE core with single-chain variable fragments (scFvs) targeting **EGFR** (epidermal growth factor receptor) and **CD3** on T cells, flanked by two unstructured, hydrophilic **XTEN** polypeptide masks attached via protease-cleavable linkers. The masks sterically block activity and extend half-life (~4 days), reducing on-target, off-tumor toxicity; tumor microenvironment proteases (e.g., matrix metalloproteinases, serine proteases, cysteine proteases) cleave the masks to activate the potent unmasked TCE (uTCE), enabling T-cell redirected cytotoxicity against EGFR-expressing tumors. Preclinical data show >4,000-fold masking protection in vitro (EC50 shift), complete tumor regressions in HT-29 colorectal xenografts (KRAS/BRAF mutant) at doses near unmasked TCE, and >200-fold higher tolerated exposure (MTD 1 mg/kg IV) in cynomolgus monkeys vs. uTCE, with low immunogenicity risk from prior XTEN clinical data. Primarily for EGFR+ solid tumors, including KRAS-mutant colorectal cancer.