The FDA has accepted an investigational new drug application for ZW25 (Zymeworks Inc.), a bi-specific antibody, for the treatment of certain human epidermal growth factor receptor 2 (HER2)-expressing cancers. The phase 1 clinical trial is anticipated to begin later this month.
ZW25 is an engineered bi-specific antibody that targets two different epitopes (bi-paratopic targeting) of the HER2 protein, which is overexpressed on the surface of many tumor types, including certain breast, gastric, lung, and ovarian cancers. ZW25 has multiple mechanisms of action, including: 1) enhanced antibody-mediated effector function resulting from the increased decoration of the tumor cell surface; 2) increased blockade of the HER2 cellular growth signal by the dual engagement of HER2 epitopes; and 3) increased removal of surface-expressed HER2 proteins resulting from enhanced HER2 internalization upon antibody engagement.
ZW25 was developed using the Azymetric platform. Bi-specific antibodies using this platform resemble conventional mono-specific antibodies while being able to bind simultaneously to two different targets, resulting in additive or synergistic therapeutic responses. Azymetric antibodies spontaneously assemble into a single molecule with two different Fab domains comprising unique heavy and light chain pairings. These antibodies are manufactured using conventional monoclonal antibody processes and can be adapted to rapidly screen target and sequence combinations for bi-specific activity in the final therapeutic format, thereby significantly reducing drug development timelines, according to Zymeworks.
ZW25 will be evaluated for safety and efficacy in patients with tumors with low-to-moderate levels of HER2 expression.
The FDA previously granted an orphan drug designation to ZW25 for the treatment of patients with ovarian cancer.
Source: Zymeworks; August 18, 2016.