Building Better Biologics™

POWERFUL, VERSATILE PROTEIN ENGINEERING PLATFORMS FOR HIGHLY CUSTOMIZED THERAPEUTICS INCLUDING MULTISPECIFIC BIOLOGICS, ANTIBODY DRUG CONJUGATES, AND IMMUNO-ONCOLOGY THERAPIES

Building Better Biologics™

POWERFUL, VERSATILE PROTEIN ENGINEERING PLATFORMS FOR HIGHLY CUSTOMIZED THERAPEUTICS INCLUDING MULTISPECIFIC BIOLOGICS, ANTIBODY DRUG CONJUGATES, AND IMMUNO-ONCOLOGY THERAPIES

Zanidatamab

Zanidatamab

HER2-Targeted Bispecific Antibody
developed using Zymeworks proprietary Azymetric™ platform

HER2-Targeted Bispecific Antibody
developed using Zymeworks proprietary Azymetric™ platform

Zanidatamab:

Zanidatamab, is a HER2-targeting Bispecific Antibody developed using Zymeworks proprietary Azymetric™ platform.

Zanidatamab is currently being evaluated in Phase 1, Phase 2 and pivotal clinical trials as a treatment for patients with HER2-expressing cancers, including biliary tract, gastroesophageal adenocarcinomas, breast, and other tumor types.

Zanidatamab has been granted Breakthrough Therapy designation for biliary tract cancer from the FDA, as well as two Fast Track designations, one for previously treated or recurrent HER2-positive biliary tract cancer and another for first-line gastroesophageal adenocarcinoma in combination with standard of care chemotherapy. Zanidatamab also received Orphan Drug designations for the treatment of biliary tract, gastric and ovarian cancers in the United States and for biliary tract and gastric cancer in the European Union.

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Unique Mechanisms of Action

Zanidatamab is designed to bind to two distinct sites on HER2, a protein expressed on many types of cancer cells.

The extracellular domain of the HER2 receptor comprises four domains, with zanidatamab binding to epitopes on domain 2 and domain 4.

This unique geometry enables, zanidatamab to crosslink neighbouring HER2 proteins resulting in multiple mechanisms of action demonstrated in preclinical research. These include HER2 receptor clustering, internalization and downregulation; inhibition of growth factor-dependent and -independent tumor cell proliferation; antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP); and complement-dependent cytotoxicity (CDC).

FAB

Targets the dimerization domain ECD2 on HER2

Fc

Heterodimeric Fc facilitates interactions with the immune system, including antibody dependent cellular cytotoxicity (ADCC), antibody dependent cellular phagocytosis (ADCP) and complement-dependent cytotoxicity (CDC). The orientation of the Fc region of zanidatamab in a HER2-zanidatamab cell surface cluster allows binding of complement proteins and killing of HER2 overexpressing cancer cells via CDC.

scFV

Targets the juxtamembrane extracellular domain ECD4 on HER2

Unique Mechanisms of Action

Zanidatamab is designed to bind to two distinct sites on HER2, a protein expressed on many types of cancer cells.

The extracellular domain of the HER2 receptor comprises four domains, with zanidatamab binding to epitopes on domain 2 and domain 4.

This unique geometry enables, zanidatamab to crosslink neighbouring HER2 proteins resulting in multiple mechanisms of action demonstrated in preclinical research. These include HER2 receptor clustering, internalization and downregulation; inhibition of growth factor-dependent and -independent tumor cell proliferation; antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP); and complement-dependent cytotoxicity (CDC).

Visit our website for more information about the AZYMETRIC Platform

Visit the website for more information on zanidatamab clinical trials