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 FDA has granted Orphan Drug Designation for ZW33 for the treatment of ovarian cancer. 

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:

  • Enhanced toxin-mediated cytotoxicity and tumor growth inhibition due to increased HER2-mediated ADC internalization;

  • Increased ZW33-mediated HER2 internalization, which reduces HER2-mediated signaling and results in tumor growth inhibition and apoptosis;

  • Enhanced effector function-mediated cytotoxicity including ADCC, CDC and ADCP as a result of increased binding/decoration of the tumor cells by ZW33. Enhanced phagocytosis and presentation of HER2 antigen may also lead to increased immune targeting of the tumors; and

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