ZW49

Anti-HER2 x HER2 ADC Overview

ZW49 is a bispecific anti-HER2 ADC that is based on the same antibody framework as ZW25 but armed with a cytotoxic payload. ZW49 retains the mechanisms of action of ZW25 but takes advantage of high levels of antibody-target internalization to deliver our proprietary ZymeLinkTM cytotoxic payload. We intend to develop ZW49 for several indications characterized by HER2 expression including breast cancers that have progressed or are refractory to existing HER2-targeted therapies, and other HER2 expressing solid tumors. We plan to file an IND Application for ZW49 in 2018.

ZW49 can potentially mediate its therapeutic effect on HER2-expressing tumors through a combination of mechanisms, including:

  • cross-linked trans HER2 binding and HER2 receptor clustering;

  • increased HER2-mediated antibody internalization leading to:

    • enhanced toxin-mediated cytotoxicity and tumor growth inhibition;

    • enhanced HER2 downregulation;

  • increased maximum binding density and potent effector-function mediated cytotoxicity; and

  • enhanced blockade of ligand-dependent and ligand-independent tumor growth.