TriTCE Co-Stim

**TriTCE Co-Stim** is Zymeworks' proprietary platform for next-generation trispecific T cell engagers (TriTCEs) designed to treat solid tumors with low T cell infiltration and poor T cell function. It simultaneously engages a tumor-associated antigen (TAA, e.g., CLDN18.2 or DLL3), CD3 (signal 1 for T cell activation), and CD28 (signal 2 costimulation) in a single molecule, engineered via Azymetric and EFECT platforms for conditional CD28 binding dependent on CD3 co-engagement, obligate cis T cell binding to prevent cross-linking, and tumor antigen-dependent activation to enhance T cell proliferation, survival, cytotoxicity, and durability while minimizing systemic cytokine release and toxicity. Preclinical data show superior antitumor activity, T cell fitness, and safety (e.g., well-tolerated in NHP repeat dosing) compared to bispecific T cell engagers like AMG 910 or AMG 757 in gastric, SCLC, and other models.[1][2][4][5]