Objective

Affimer biotherapeutics are a new protein scaffold with great potential for the generation of biotherapeutics. Based on the human protease inhibitor Stefin A, the scaffold is small (12kDa), lacks any post translational modifications such as disulphide bonds and glycosylation. Large diverse libraries have been created by engineering in two peptide loops into the scaffold backbone. Using phage display, we have identified competitive binders to a range of targets, including the immune check point, Programmed death-ligand 1 (PD-L1). PD-L1 plays an important role in immune homeostasis and blockage of the PD-L1/PD-1 pathway using antibodies has demonstrated impressive anti-tumour responses in cancer patients. Our current inhibitors have been shown to be highly selective for PD-L1 with K_D's of single digit nM as determined by BIAcore. We have shown that the scaffold is amenable to being engineered to make multimers (dimers, trimers and tetramers) as well as being formatted to extend the serum half-life.