Children under the age of 5 years account for more than 75% of deaths attributable to malaria. The World Health Organization (WHO) has recommended the vaccine Morsquirix for paediatric use, but it has modest efficacy. Monoclonal antibodies and other complementary strategies are critically important in efforts to eradicate this disease.
A multi-disciplinary team of scientists from multiple organizations collaborated on a project to select and engineer a potent and long-lasting antibody drug with anti-malaria activity. Key to this mission was to develop an antibody with developability properties amenable for cost-effective manufacturing and dosing in paediatric populations.
Scientists from Just – Evotec Biologics played a crucial role in the project. They helped with the lead candidate selection by ranking a panel of human-derived potential antibody candidates for developability using Just – Evotec Biologics’ in silico Abacus tool. Abacus is a component of our J.MDTM Molecular Design suite of tools for antibody research and development. Once the team had selected a lead and backup candidates, Just – Evotec Biologics scientists designed optimized variants of the candidate antibodies with greatly improved developability properties informed by stability violations found with the Abacus tool.
Scientists used stable pools to express the optimized designs and generate material for biophysical characterization and activity assays. This enabled the final lead selection of AB000224 and AB007088 for advancement as a clinical lead and backup. The team engineered the variable domains of both antibodies to enable low-cost manufacturing at scale for distribution to paediatric populations.
Just-Evotec Biologics scientists identified the best-producing clonal cell line, expressing the candidate molecule in continuous-perfusion bioreactors at twice the original titre. They advanced the candidate into production following good manufacturing practices. The material generated from this production run is being used to support studies for clinical development of an antimalaria drug suitable for use in paediatric populations living in Low to Middle Income Countries.
Learn more in the following article published in the prestigious journal, Nature Medicine.