Anti-HER2 x HER2 ADC Overview

ZW33 is a bispecific anti-HER2 ADC that is based on the same antibody framework as ZW25 but armed with a cytotoxic payload. ZW33 retains the mechanisms of action of ZW25 but takes advantage of high levels of antibody-target internalization to deliver a potent cytotoxin. We are developing ZW33 as a best-in-class HER2-targeting ADC for several indications characterized by HER2 expression including breast and ovarian cancer, especially those that have progressed or are refractory to HER2-targeted agents, including Kadcyla. 

The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for ZW33 for the treatment of ovarian cancer. IND filing for ZW33 is anticipated in the second half of 2017.

ZW33 can potentially mediate its therapeutic effect on low HER2-expressing tumors by the bi-paratopic targeting of HER2 resulting in:

  • Increased HER2-mediated antibody internalization leading to:
    • Enhanced toxin-mediated cytotoxicity and tumor growth inhibition
    • HER2 downregulation
  • Increased maximum binding density and potent effector function-mediated cytotoxicity
  • Cross-linked trans HER2 binding and HER2 receptor clustering
  • Enhanced blockade of ligand-dependant and ligand-independant tumor growth