Anti-HER2 x HER2 Bispecific Overview

ZW25 is Zymeworks’ lead product candidate currently being evaluated in an adaptive Phase 1 clinical trial in the United States, based on Zymeworks’ Azymetric platform.

ZW25 is a bispecific antibody that can simultaneously bind two non-overlapping epitopes, known as biparatopic binding, of HER2 resulting in dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and enhanced effector function. These combined mechanisms of action have led to significant anti-tumor activity in preclinical models of breast cancer.

Zymeworks is developing ZW25 as a best-in-class HER2-targeting antibody intended as a treatment option for patients with HER2-expressing cancers.

For more information regarding the ongoing Phase 1 trial, please visit


ZW25 can potentially mediate its therapeutic effect on low HER2-expressing tumors by the bi-paratopic targeting of HER2 resulting in:

  • Increased maximum binding density and potent effector function-mediated cytotoxicity
  • Cross-linked trans HER2 binding and HER2 receptor clustering
  • Enhanced antibody internalization and HER2 downregulation
  • Enhanced blockade of ligand-dependent and ligand-independent tumor growth