Leading the Way in Life Science Technologies

GEN Exclusives

More »

GEN News Highlights

More »
November 13, 2017

Janssen to Develop Bispecific Antibodies Based on Zymeworks Platforms in Up-to-$1.4B Deal

  • Johnson & Johnson’s Janssen Biotech will use Zymeworks’ Azymetric™ and Effector Function Enhancement and Control Technology (EFECT™) platforms to research, develop, and commercialize up to six bispecific antibodies directed to unspecified Janssen therapeutic targets, through a licensing agreement that Zymeworks said today could generate for it up-to-$1.4 billion-plus.

    The collaboration is Zymeworks’ sixth with a biopharma giant, and the first since its wholly owned lead product candidate ZW25, developed through Azymetric, entered clinical trials.

    “The proceeds from this collaboration will be primarily used to fund the clinical advancement of ZW25, as well as the advancement of our preclinical programs into the clinic,” Zymeworks president and CEO Ali Tehrani, Ph.D., said in a statement.

    ZW25 is a bispecific antibody designed to treat HER2-expressing cancers by simultaneously binding two non-overlapping epitopes—called biparatopic binding—of HER2, resulting in dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and enhanced effector function.

    According to Zymeworks, the combined mechanisms of action have led to significant antitumor activity in preclinical models of breast cancer.  ZW25 is the subject of a Phase I trial that is recruiting patients with locally advanced (unresectable) and/or metastatic HER2-expressing cancers—including breast, gastric, and ovarian cancers (NCT02892123).

    Zymeworks’ Azymetric platform is designed to develop immunoglobulin G (IgG)-like, novel bispecific antibodies capable of binding two different targets in order to target synergistic drug targets, by enabling the transformation of monospecific antibodies. The company says its Azymetric bispecific antibodies retain the desirable features of typical monoclonal antibodies, including standard manufacturing processes with comparable production yields, long serum half-life, the ability to mediate effector function, and low immunogenicity risk.

  • Cause and EFECT

    The EFECT platform consists of a library of fragment crystallizable (Fc) modifications designed to selectively modulate the activity of recruited immune cells, including upregulation to enhance antibody-mediated effector cytotoxicity and downregulation to suppress unwanted effector activity for certain therapeutic applications.  

    Through the EFECT platform, Zymeworks says, proprietary mutations are introduced to the CH2 domain of the antibody's Fc to selectively modulate an antibody’s interactions with the Fc-gamma receptors (FcγR) expressed on the surface of immune cells and with components of the complement pathway. EFECT is compatible with traditional monoclonal as well as Azymetric bispecific antibodies to further enable the customization of therapeutic responses for different diseases, the company adds.

    Janssen has agreed to oversee all research, development, and commercial activities under the licensing agreement. In return, Janssen has agreed to pay Zymeworks $50 million upfront, up to $282 million in payments tied to achieving development milestones, and up to $1.12 billion in commercial milestone payments, plus tiered royalties on potential sales.

    Under the agreement with Zymeworks, Janssen also has the option to develop two additional bispecific programs subject to a future option payment.

    In addition to ZW25, Zymeworks’ pipeline includes numerous preclinical candidates—the bispecific anti-HER2 antibody–drug conjugate (ADC) ZW33, in development to treat breast and ovarian cancer, as well as unspecified bispecific ADCs, T-cell-engaging bispecifics, and checkpoint-modulating bispecifics, all indicated to treat solid tumors.

    Janssen joins Celgene, Daiichi-Sankyo, GlaxoSmithKline, Eli Lilly, and Merck & Co. in establishing collaborations with Zymeworks.

Related content

  • Finally! A cure for the Biotech News Blues.

  • Join 110,000 colleagues who rely on GEN Highlights for breaking news and exclusive articles shaping today’s life science tools and technologies.

  • Oops! Please type your email in the following format: [email protected] An error has occurred. Please contact Customer Service at [email protected]
  • You’re all set! Thank you for subscribing to GEN Highlights.