The Rise of Multi-specific NANOBODY® molecules in Pharmacokinetic Assays

Pharmacokinetic (PK) ligand binding methods measure the concentration of biotherapeutics such as NANOBODY® molecules in biological samples to support regulatory filings. Assay formats are designed to measure free, bound, functional (active) or total drug depending on project requirements. Multi-specific NANOBODY® molecules bind multiple targets and thus pose additional challenges for developing PK methods.

Three different fit-for-purpose PK formats were developed for bi-specific NANOBODY® molecules to evaluate PK properties and provide distinct information on drug behavior in vivo in the presence of interference factors such as anti-drug antibodies (ADA) and target. A total assay format was suitable to evaluate PK properties for research-stage candidates, a bi-active method allowed measurement of active exposure for both target domains for later-stage studies and a mono-active assay provided information on the functionality of the compound related to each individual target. In vivo data showed a good correlation for the total assay compared to the mono-active and bi-active assays, although expected interference from target and/or ADA was observed in the bi-active assay in some dose groups.

In summary, a variety of well-characterized PK assays provide a complete data package to support PK modeling for complex multi-specific NANOBODY® molecules throughout the lifespan of a project.

Authors

Valentine Allemon, Katrien van Lysebetten, Sofie Poelmans, Thomas Antoine and Samuel Pine

Organisations

Ablynx, a Sanofi company

Presenting author

Valentine Allemon, Associate Scientist, Ablynx, a Sanofi company
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