Amsterdam-based Kling Bio has entered a collaboration and license-option agreement with Sanofi to accelerate the discovery of neutralizing antibodies using its proprietary Kling-Select B-cell platform. The platform leverages immortalized, patient-derived human B cells and function-first screening to rapidly identify potent monoclonal antibodies and conserved viral epitopes, with validated candidates against RSV, COVID-19 and influenza. The ultimate goal is to identify neutralizing antibodies and their respective epitopes against an undisclosed human viral pathogen and to accelerate the discovery of neutralizing antibodies.
Identifying neutralizing antibodies against a pathogen is a time consuming process that typically requires structural understanding the target epitope and de novo generation of antibodies to bind it. Those antibodies are then tested using virus neutralization assays, but Kling Bio’s CEO Michael Koslowski says that their approach is different. “We do not need prior knowledge of the target because we use biosamples from individuals who’ve recovered from the infection and thus already have a functional immune response. We produce B cell libraries that retain the full diversity of the antibody response present in these individuals with our proprietary B cell immortalization technology. We can then directly screen the immortalized libraries to identify antibodies in functional assays – like virus neutralization assays – without first confirming binding. This function-first approach is more efficient than traditional antibody discovery.”
The RSV antibody marketed by Sanofi and AstraZeneca, Beyfortus (nirsevimab), was discovered using the same technology. Interestingly, the antibody doesn’t bind the virus especially strongly, but targets a functional epitope present just before the virus attaches to a cell. “That’s not an antibody you’d normally select in a traditional discovery campaign,” Koslowski adds, “which often focuses on high affinity binders.”
Kling’s technology helps identify these novel, functionally relevant epitopes. In the Sanofi collaboration, the same platform is used to screen samples for a different human viral pathogen. Once a promising antibody is identified, focus can return to the original, immortalized B cell. The IG genes are then cloned and a fully human antibody is rapidly produced. The process takes only three to four weeks.
Koslowski says, “In contrast, conventional approaches can take months just to identify a functional hit. That’s what we mean by accelerated discovery."
The collaboration will last for two years with multiple screening rounds. In a conventional two-year program starting from de novo antibody generation, a biotech would be content to have validated hits by the end. The expectation of the collaboration with Sanofi, however, is to identify functional hits early – potentially multiple antibodies – long before the collaboration concludes.
For Kling’s part, the Amsterdam-based biotech will take responsibility for handling antibody identification, initial screening, and library preparation. In partnership with Sanofi, neutralization assays will be conducted in a shared research agreement. “We bring our expertise in producing immortalized B cell libraries and single-cell characterization workflows,” Koslowski says, “Sanofi contributes their functional testing capabilities as they’ve already set up the necessary assays.”
Sanofi has an exclusive option to license, develop, and commercialize the antibodies either directly or as vaccine candidates, if the epitopes prove useful. The initial focus is on a single, clinically relevant human viral pathogen in the area of infectious diseases.
“We have invested heavily in building an unmatched discovery platform with validated results in the infectious disease contexts,” Koslowski concluded. “We're also expanding its use into oncology. Our internal preclinical pipeline currently includes two novel oncology targets, demonstrating the technology’s versatility.”
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