Gandeeva, Zymeworks Using Cryo-EM to Enhance Antibody Drug Discovery

Editor’s Take: The companies hope their partnership is a gamechanger in accelerating AI-driven antibody design.

Gandeeva Therapeutics and Zymeworks are partnering on cryo-electron microscopy (cryo-EM)-driven drug design, to visualize antibody-antigen interface structures at high resolution.

Paul Moore, PhD, Zymeworks Chief Scientific Officer, explained the reasons behind the collaboration.

“Knowledge of the precise interactions at the binding interface of these types of challenging targets is incredibly useful,” Moore said. “It provides us with crucial insights for the optimization of biologics.”

What is Cryo-EM?

Cryo-EM routinely determines structures of antibody complexes formed with compact, well-folded antigens. However, mapping antibody epitope footprints on small, flexible antigens continues to be challenging, according to the two companies.

Their collaboration has already borne fruit. Scientists at Gandeeva determined the structure of a small and flexible antigen bound to the Fab fragment of a Zymeworks-developed antibody.

Gandeeva CEO Enthusiastic

Gandeeva Founder and CEO Sriram Subramaniam, PhD, said the determination represents a step forward.

“Our ability to obtain near-atomic resolution cryo-EM structures … within flexible and structurally intractable proteins is a game-changer,” Subramaniam said. “Experimental validation by high-resolution and high-throughput cryo-EM using Gandeeva’s platform provides exactly the kind of rapid feedback that is essential.”

Zymeworks Pipeline Expanding

Gandeeva’s purpose-built headquarters facility in Vancouver features state-of-the-art cryo-EM instrumentation. It will now support Zymeworks’ portfolio of licensed healthcare assets and pipeline of novel, multifunctional biotherapeutics. These include difficult-to-treat conditions such as cancer, inflammation, and autoimmune disease.

Zymeworks additionally said it wants to leverage expertise in antibody-drug conjugates and multispecific antibody therapeutics in areas of unmet need.