As a result of the COVID-19 pandemic and its dramatic impact on life around the world, biopharmaceutical R&D laboratories were tasked with discovering and developing monoclonal antibodies (mAbs) using novel strategies on highly accelerated timelines.  With this urgent need in mind, AstraZeneca streamlined the typical drug discovery and development activities in an effort to bring COVID-19 antibody therapies to patients as quickly as possible while ensuring that the mAbs met the highest standards of potency, developability and stability. In this presentation, we describe the seamless collaboration between our antibody discovery and protein engineering (ADPE) group and our early stage bioprocess development (BPD) group.  The unified team effort characterized 60 potential mAb candidates in less than 7 weeks. Following expression and purification, the mAbs were tested in SARS-CoV-2 in a pseudo-virus neutralization assay, epitope binning assay and in silico sequence liability assessments were performed to narrow the mAb candidates to the top 10 mAbs.  The selection of the top two antibodies to enter clinical development was determined by epitope mapping experiments to ensure that the mAbs bound to distinct, non-overlapping regions on the receptor binding domain of the Spike protein and ranking the developability of the mAbs using a combination of techniques including platform expression and purification, liquid stability, analytical method fit, and coformulation assessments.  The activities described in this work, performed under pandemic restrictions and lockdowns, resulted in the identification of two highly potent mAbs and enabled their progression to full clinical development in 11 weeks.

Accelerated lead selection and developability assessments for AstraZeneca’s SARS-CoV-2 long acting antibody (LAAB) combination for the prevention and treatment of COVID-19

ACS Fall 2021

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