BIOLOGICS
New biologics from glycan binding decoy protein technology
ProtAffin AG is developing glycan-binding decoy proteins based on human chemokines and other protein families, representing a novel class of next-generation biopharmaceuticals for respiratory disease, inflammation and oncology. Dr Jason Slingsby, the company’s CEO, explains how it has generated a broad product pipeline using its proprietary technology for the discovery of novel biologics.
iologics company ProtAffin was co-founded by Professor Andreas Kungl, who identified the potential to make protein-based drugs that target glycans, and Dr Jason Slingsby. Glycans are carbohydrate chains displayed on the surface of endothelial cells, and play a crucial role in many disease-linked processes, including inflammation and the development and spread of cancer. Professor Kungl is a world-leading expert in carbohydrate-protein interactions and recognised the potential to develop novel drugs that bind to glycans, offering a completely novel approach to many diseases in the inflammatory and oncological fields.
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The company was spun out of the University of Graz, where Professor Kungl was based, and received significant support from AWS, a fund set up by the Austrian Government providing seed and start-up capital to biotechnology companies. INiTS, an Austrian incubator for biotech and other high-tech start-ups, also played an important role in supporting the founders when they set up the company in 2005.
ProtAffin has 25 employees and is headquartered in Graz, Austria with a London-based UK office housing its regulatory and clinical development functions. The company has raised €19 million in venture capital and investors include Aescap Venture, Atlas Venture, SROne, Entrepreneurs Fund and Z-Cube. It has also raised a further €6 million in non-dilutive financing from groups including AWS and FFG, an Austrian body that awards research grants to Austrian companies.
An alternative to small molecules and mAbs
Glycan-binding decoy proteins represent an alternative to traditional small-molecule therapeutics and monoclonal antibodies and specifically block the action of proteins such as chemokines which are active when they are bound to specific glycans: “The key piece of the biological puzzle is that many proteins – with chemokines being one of the best examples – are controlled by and function only through their interaction with glycans,” explains Slingsby. “ProtAffin blocks
the action of this type of protein by developing novel biologicals that specifically displace the protein from glycans, preventing them from functioning. Our CellJammer® discovery technology allows us to develop a decoy against any glycan-binding protein. The decoy is based on the molecule we want to downregulate and has two specific, rationally designed changes that we introduce: first, increasing the affinity for the glycan chain, and second, removing the ability to activate its target cell. These changes mean – if we take chemokines as an example – that our decoy displaces the active inflammatory chemokine from glycans but does not cause recruitment of leukocytes since the decoy molecule is inactivated. “For instance, our lead product PA401 blocks the action of IL-8, inhibiting neutrophil recruitment and thus reducing neutrophil- related inflammation and damage, so we have, in effect, turned the pro-inflammatory IL-8 chemokine into an anti-inflammatory biologic agent.”
Inflammatory chemokine IL8 bound to a glycosaminoglycan molecule. 26 sp2 Inter-Active March/April 2012
Slingsby says ProtAffin’s approach differs from other biological approaches in a number of important mechanistic and pharmacologically-relevant ways: “If you take mAbs, for example, they are often very good at targeting soluble proteins but not so effective at recognising and blocking the action of glycan-bound proteins. So any protein that is active when bound to a glycan may not be best addressed by using monoclonals. Also, since mAbs only address a single or few targets, as in the case of bi- specifics, they are not ideal for reducing an inflammatory process that has multiple mediators. In contrast, we have shown that our glycan-decoys displace multiple inflammatory proteins from glycans thus resulting in a broader anti-inflammatory response. “As we are the only company capable of targeting glycans, and have broad IP both
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