Characterising nanobody developability to improve therapeutic design using the Therapeutic Nanobody Profiler

Developability optimisation is an important step for successful biotherapeutic design. For monoclonal antibodies, developability is relatively well characterised. However, progress for novel biotherapeutics such as nanobodies is more limited. Differences in structural features between antibodies and nanobodies render current antibody computational methods unsuitable for direct application to nanobodies. Following the principles of the Therapeutic Antibody Profiler (TAP), we have built the Therapeutic Nanobody Profiler (TNP), an open-source computational tool for characterising nanobody developability. Tailored specifically for nanobodies, it accounts for their unique properties compared to conventional antibodies for more efficient development of this novel therapeutic format. We calibrate TNP metrics using the 36 currently available sequences from clinical-stage nanobody-based drugs. We also collected experimental developability data for 108 nanobodies expressed as IgG constructs and examine how these results are related to the TNP guidelines. TNP is available as a web application at opig.stats.ox.ac.uk/webapps/tnp.