Fig. 1: Zanidatamab is a biparatopic anti-HER2 Ab that binds HER2-expressing tumor cells with greater Ab saturation than trastuzumab or pertuzumab.

a Zanidatamab is a humanized, biparatopic, immunoglobulin 1 (IgG1)-like Ab with an scFv (light blue) that binds the juxtamembrane ECD4 of HER2 and a Fab (dark blue) that binds the ECD2 dimerization domain of HER2, the same domains targeted by trastuzumab and pertuzumab, respectively. b Representative class-averaged TEM image, derived from 216 images, showing the 3-lobed structure of zanidatamab with putative assignments of the scFv, Fab, and Fc region from a single experiment. c Zanidatamab binds with greater Ab saturation to tumor cell lines compared to trastuzumab or pertuzumab. Flow cytometry was used to quantify the binding of zanidatamab, trastuzumab, pertuzumab, and tras + pert (1:1) to SK-BR-3 tumor cells. In c, data are mean ± SEM from n = 3 independent experiments. Gating strategy for Ab binding to SK-BR-3 cells (c) is shown in Supplementary Fig. 11a. Source data are provided in the Source Data file.