Merck & Co. negotiated a worldwide license to use Zymeworks’ Azymetric™ platform for the development and commercialization of bispecific antibodies against targets in multiple therapeutic fields. The companies will work together to continue developing the platform, while Merck will take any resulting bispecific antibody products through clinical development.
Under terms of the deal Zymeworks will receive an up-front fee and could earn research, development, and regulatory milestones of up to $187 million. Merck retains exclusive worldwide commercialization rights to products derived from the partnership. “This is an important validation of our scientific leadership in the field of structure-guided protein engineering,” comments Ali Tehrani, Ph.D., Zymeworks CEO. “We look forward to working with Merck and to realizing the full value of this novel platform technology across a range of therapeutic indications.”
The firm’s Azymetric platform exploits an IgG1-based heterodimeric antibody scaffold that consists of two different heavy chains engineered to assemble into a single molecule, which allows bispecific binding to two different antigens or drug targets. The scaffold has been developed by incorporating specific amino acid changes in the CH3 region of the constant Fc domain of a native IgG1 class antibody. Zymeworks claims that in addition to providing bispecificity, the Azymetric scaffold allows for the design of tailored effector function and optimized serum half-life.
The bispecific antibody platform has been developed using the firm’s ZymeCAD™ platform for protein modeling and structure-guided protein engineering. ZymeCAD consists of a suite of algorithms that allows the development of models of a protein therapeutic molecule’s structure and complexes with targets, the optimization of conformation, and analysis of the dynamics of resulting protein therapeutics.
In addition to its Azymetric platform, Zymeworks is developing a monoclonal antibody technology known as the Effect™ (effector function enhancement and control technology) platform, which allows the engineering of optimized monoclonal antibody constant regions with tailored effector function. Effect antibodies comprise IgG1 antibody Fc domains that display highly selective and specific binding to various FcγR, to enable the enhancement or suppression of antibody dependent cellular cytotoxicity, the firm claims.
Complementing the Azymetric and Effect platforms is a multivalent antibody-alternative protein scaffold AlbuCORE™, which is smaller than traditional antibodies, allowing both improved tissue penetration, but also the multivalent crosslinking of disease targets. The firm claims advantages of the AlbuCORE scaffold include its lack of innate effector function, low immunogenicity, potential for manufacture in bacterial systems, and long serum half life.