ZW209

ZW209 is a novel trispecific T cell engager (TriTCE) developed by Zymeworks. It targets Delta-like ligand 3 (DLL3), a cell surface protein overexpressed in small cell lung cancer (SCLC) and other neuroendocrine carcinomas. The molecule is engineered to co-engage CD3 and CD28 on T cells, integrating both T cell activation and co-stimulation for enhanced anti-tumor activity. Built using the Azymetric™ and EFECT™ platforms, ZW209 leverages obligate cis-T cell binding with conditional CD28 engagement to prevent unintended T cell activation while enabling potent tumor-targeted cytotoxicity. Preclinical studies demonstrate that ZW209 provides superior cytotoxicity compared to traditional bispecific T cell engagers, with prolonged activity at low effector-to-target ratios, increased durability of response, enhanced T cell proliferation/survival, and an encouraging safety profile in non-human primates[1][5][6][8][9][10].