Streamlining bispecifics

BASEL, Switzerland—Genedata, a leading provider of advanced software solutions for R&D, will help German pharma giant Merck KGaA to scale up its bispecific antibody discovery programs in order to develop innovative therapeutics for oncology, immunology and neurodegenerative diseases. Merck will use Genedata Biologics functionalities to streamline the design, production and testing of bispecific antibodies across its therapeutic R&D programs.

According to Genedata, the need to systematically evaluate large panels of multispecific antibodies poses new bottlenecks for antibody engineering in terms of throughput and automation. Multiple next-generation antibody formats must be tested, resulting in significant combinatorial complexity. Genedata Biologics substantially increases throughput by enabling the systematic design and cloning of large numbers of novel, highly engineered molecules and enabling automation of downstream expression, purification and characterization processes, the company said.

In 2015, Merck deployed Genedata Biologics as its central biologics workflow platform across Merck Biopharma antibody discovery units in Germany, Israel and the United States, where Merck operates its biopharmaceutical business as EMD Serono. The platform’s applications have been expanded to groups including phage and yeast display, B cell cloning, protein engineering, microbial and mammalian expression, purification, analytics and quality control. Now Genedata Biologics is Merck’s central repository for biologics candidate data, enabling transparent decision-making on the most promising candidates to promote into clinical development.

According to Dr. Othmar Pfannes, CEO of Genedata, “We are delighted to see Merck expand the application scope of Genedata Biologics to its innovative bispecific R&D programs. It is exciting to see how our platform enables the adoption of new processes in this quickly evolving field. We are committed to further expanding the platform in close collaboration with our growing customer base to support new technologies, such as cell and gene therapies, RNA therapeutics, novel scaffolds and other innovative therapeutic platforms.”

As he explained, Genedata Biologics is a scientific enterprise software platform that comprehensively addresses large molecule R&D workflows (e.g., antibody generation and screening, protein engineering, protein production, bioprocessing, comprehensive medicinal chemistry). It is currently in use at top biopharma organizations in Europe and in the United States.

Many novel biologic molecules such as bispecific and multispecific antibodies, non-Ig or alternative scaffolds, chimeric antigen receptors and high affinity T cell receptors have gained significant attention in the industry because of the unique therapeutic advantages they can confer via new modes of action, and many of these novel formats are now successfully in the clinic. These molecules are highly engineered and pose significant challenges in cloning/molecular biology, expression, purification and characterization. The engineering work typically requires producing and screening large panels of these molecules. For example, for affinity optimization, these may be variants resulting from single-point or combinatorial mutations; for bispecific/multispecifics, variants may be due to format-specific parameters (varying linker lengths, linker combinations, valency, and binder/variable domain positions); for antibody-drug conjugates, variants result from to conjugation chemistry, position, linker design, toxin and drug loading.

The Genedata Biologics platform offers the ability to systematically and automatically track and register all engineered molecules and their molecule and production genealogy (e.g., plasmids/vectors, cell lines, expression batches, purification batches). With its unique highly structured database and built-in biologics domain knowledge, the platform is able to handle novel molecule formats and corresponding novel cloning and platform production processes very flexibly. The platform can direct laboratory automation, such as for DNA amplification, cloning, transient transfection and protein purifications, to allow performance of these steps in high throughput. The automation extends to highly automated data processing and submission to the centralized database of a wide range of functional assay and analytic results. All data are made centrally accessible for timely and knowledge-based decision-making by scientists and research leaders in the laboratory, across multiple, often global, sites.

“Using the platform, we have enabled several organizations to industrialize their novel antibody technology platforms, taking operations from the scale of tens of molecules handled manually in the lab to panels of tens of thousands of molecules with automation,” Pfannes said. “These days, we work with design panels in the order of millions of molecules. Genedata is deeply involved at the forefront of the biopharma industry’s efforts to discover and develop these very promising new therapeutic molecules.”

This is an ongoing and continuous partnership, according to Pfannes. Merck may use the Genedata Biologics platform for its various biologics R&D workflows today and as the programs evolve in the future.

“Our customers report up to 50-percent gains in efficiency and throughput as well as improved quality of results,” Pfannes concluded. “This is accomplished by tracking and managing all molecules, samples and testing data in one shared system.”