Gandeeva and Zymeworks partner on cryo-EM antibody structure work

Gandeeva Therapeutics, Inc. and Zymeworks Inc. (Nasdaq: ZYME), both based in Vancouver, Canada, have formed a partnership to use cryo-electron microscopy (cryo-EM) to map antibody-antigen binding interfaces in support of antibody drug discovery, according to a press release.

The collaboration produced a structural result that the companies say addresses a known technical limitation. While cryo-EM is routinely used to study antibody complexes with well-folded antigens, determining structures involving small and flexible antigens has remained difficult. Gandeeva scientists determined the structure of a small antigen — under 20 kilodaltons — bound to the Fab fragment of an antibody developed at Zymeworks, resolving nine amino acids at the antibody-binding epitope at 2.6 Å resolution. The remainder of the antigen, described as highly flexible, was not resolved.

"Knowledge of the precise interactions at the binding interface of these types of challenging targets is incredibly useful for us in selecting antibody leads and provides us with crucial insights for the optimization of biologics," said Dr. Paul Moore, Chief Scientific Officer of Zymeworks.

Dr. Sriram Subramaniam, Founder and CEO of Gandeeva Therapeutics, said the ability to obtain near-atomic resolution structures of antibody binding epitopes within flexible proteins provides "rapid feedback that is essential for testing and validating antibodies derived by immunization and by computational design."

Gandeeva operates a purpose-built cryo-EM facility in Vancouver and applies its platform both to its own drug development programs and through partnerships with other biotechnology and pharmaceutical companies. Zymeworks maintains a pipeline of biotherapeutics targeting cancer, inflammation, and autoimmune disease.

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