Background on Avibodies
An Avibody consists of the key target binding domains of intact antibodies but in a much smaller format. Antibody fragments have struggled to gain traction as therapeutics due to problems with stability, manufacturing or off-target deposition. Avibodies do not have these problems yet retain the benefit of greater tumour penetrance and higher tumour deposition.
The idea of using an antibody as a ‘magic bullet’ to selectively deliver an imaging agent or toxic payload to cancer has been in active development for three decades. Amongst the many things that have been learned on that journey is that the way that the payload is conjugated is critical for efficacy and safety. Many products currently in development utilise random conjugation of payload resulting in a heterogeneous product with variable Drug-Antibody Ratios (DAR). Avipep uses proprietary protein engineering to position conjugation sites on the accessible surface of the Avibody resulting in DAR of exactly two or four per Avibody depending on the chemistry utilised for conjugation.
Avipep can take an existing antibody and ‘reformat’ it into an Avibody. Using molecular modelling, conjugation sites can then be engineered into the Avibody. Avipep has a collaboration with Affinity Bio to utilise its retained display (ReD) system for the generation of Avibodies starting with the target protein. This approach has the advantages of speed both in the selection of the Avibody and because the conjugation sites are already engineered into the library.