Gandeeva and Zymeworks Use Cryo-EM to Resolve Antibody Epitopes on Flexible Antigens at Near-Atomic Resolution
核心洞察
Gandeeva Therapeutics (搜索) and Zymeworks have partnered to apply cryo-EM for high-resolution structural mapping of antibody-antigen interfaces to accelerate drug discovery.
Gandeeva scientists successfully resolved the nine-amino-acid antibody-binding epitope of a small, flexible antigen (<20 kDa) at 2.6 Å resolution, a notably challenging target class.
The structural insights enable more informed antibody lead selection and optimization of biologics, according to Zymeworks CSO Dr. Paul Moore.
Vancouver-based Gandeeva Therapeutics (搜索) and Zymeworks Inc. (Nasdaq: ZYME) have entered a partnership to generate cryo-electron microscopy (cryo-EM)–based structural data aimed at augmenting antibody drug discovery, the companies announced on June 18, 2026. The collaboration has already yielded a notable technical achievement: the near-atomic resolution visualization of an antibody-binding epitope on a small and highly flexible antigen—a class of targets that has historically resisted structural characterization by cryo-EM.
While cryo-EM is now used routinely to determine structures of antibody complexes formed with compact and well-folded antigens, mapping antibody epitope footprints on small and flexible antigens remains highly challenging. Gandeeva scientists have now determined the structure of a small and flexible antigen, measuring less than 20 kDa, bound to the Fab fragment of an antibody developed at Zymeworks. Critically, the team was able to visualize the nine amino acids that form the antibody-binding epitope at 2.6 Å resolution. The remainder of the antigen, being highly flexible, was not resolved in the reconstruction.
"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.
The advance carries particular significance for the emerging field of AI-driven antibody design. "Our ability to obtain near-atomic resolution cryo-EM structures of the antibody binding epitope within flexible and structurally intractable proteins is a game-changer, especially in the context of accelerating design of AI-driven antibodies," said Dr. Sriram Subramaniam, Founder and CEO of Gandeeva Therapeutics (搜索). "Experimental validation by high-resolution and high-throughput cryo-EM using Gandeeva's platform provides exactly the kind of rapid feedback that is essential for testing and validating antibodies derived by immunization and by computational design."
Gandeeva's proprietary platform integrates high-resolution cryo-EM imaging with advanced machine learning to streamline structure-to-drug workflows, enabling rapid, iterative analysis of complex biological targets including transient protein interfaces and membrane proteins. The company applies its platform both to its own internal drug development programs and through partnerships with other biotechnology and pharmaceutical companies.
Zymeworks brings to the collaboration its expertise in antibody drug conjugates and multispecific antibody therapeutics, with a pipeline targeting difficult-to-treat diseases including cancer, inflammation, and autoimmune disease. The company's portfolio includes licensed products such as Ziihera (zanidatamab-hrii) and other product candidates including pasritamig (搜索).
The partnership illustrates the growing role of cryo-EM as a practical tool in drug discovery, moving beyond academic structural biology into iterative, industrially relevant applications where rapid structural feedback can directly inform lead selection and optimization decisions.