Antibody-based Phenotypic Screening – the Discovery of Oleclumab (MEDI9447)

Phenotypic antibody drug discovery, which takes a target-agnostic approach, remains an under-utilised strategy in an industry where target-led antibody drug discovery is dominant. However, there are strong arguments in support of the phenotypic approach as it promises the fast-track identification of novel molecular targets as well as uncovering new areas of unexplored target biology. This chapter discusses the use of antibody phenotypic screening for the discovery of novel monoclonal antibodies and the identification of CD73 as a new oncology target. The phenotypic approach led to an early stake in the emerging area of adenosine-mediated immune suppression in tumours and led directly to the development of oleclumab, a first-in-class anti-CD73 antibody, now under investigation in clinical trials.