Blog Update from Dr Amrik Basran – Chief Scientific Officer, Therapeutics
I presented at PEGS Europe this week, a leading conference covering protein and antibody engineering for therapeutic drug development. The talk gave a potted history of Avacta and our therapeutic plans, including an update on the development of the Affimer platform with the focus being on our PD-L1 program. The main content of the talk was the demonstration that we could make Affimer fusions using our lead PDL1 binder making dimers, trimers and tetramers. The expression yields of these molecules is very good ~200 mg/L in an unoptimised process and we showed we could purify high quality product easily without seeing any breakdown products. But the most interesting data was being able to show that each Affimer in the chain was still able to bind target and in certain assays we demonstrate avidity effects which allows us to make very high affinity molecules. The tetramer of four Affimers having an affinity of ~80pM! This means that in the future, we should be able to make multi-targeting molecules, where each Affimer in the chain would bind to a different protein. With the advantage of the small size of the scaffold and being able to target several proteins involved in a disease, we’re hopeful to be able to create drugs of real therapeutic value for patients.
Following the talk, I had several discussions with people interested in learning more about the technology, how they could potentially use the platform either for reagents or therapeutics having seen the flexibility we have with the technology.
There was a real focus on cancer biotherapeutics this year at PEGS with a lot of the presentations on the preclinical and clinical development of a range of protein platforms, not just standard mAbs. There was a wide range of technologies being talked about, not just standard mAbs, but novel protein scaffolds as well. What is clear, is that there is a real move towards trying to get a clearer picture of the complex underlying biology and with that, coming up with very novel drug formats that’ll give cancer patients a better clinical outcome. Being able to target multiple proteins with a single molecule is the way forward, whether it is with a novel scaffold, highly engineered mAb or a hybrid approach of bolting on a novel scaffold onto a mAb.
DR AMRIK BASRAN
Avacta Life Sciences