BioWorld International Correspondent

ProtAffin Biotechnologie AG raised €2.65 million (US$3.6 million) in a Series A round to fund preclinical development of its protein-based drugs that are designed to disrupt protein-glycan interactions involved in pro-inflammatory signaling.

The round was led by Amsterdam, the Netherlands-based Aescap Venture Management BV, a fund established by Dinko Valerio, former CEO of Leiden, the Netherlands-based Crucell NV, and Michiel de Haan, founder of Atlas Venture, of Waltham, Mass.

"It's very much smart biotech money, and for us it was very important to get some good VCs on board as soon as possible," Jason Slingsby, co-founder and CEO of Graz, Austria-based ProtAffin, told BioWorld International. Z-Cube Srl, the corporate venture arm of Bresso, Italy-based Zambon Group, also participated in the transaction.

ProtAffin was spun out of the Karl-Franzens University of Graz in July 2005 to commercialize a method for altering the binding properties of pro-inflammatory chemokines by exploiting knowledge of their interactions with glycosaminoglycans (GAGs), linear polysaccharide chains found on the cell surface and in the extracellular matrix. Those, together with a core protein, form proteoglycans, which exhibit considerable structural diversity and which can interact with multiple ligands.

ProtAffin's CellJammer technology, developed by Chief Scientific Officer and co-founder Andreas Kungl, involves modifying the structure of GAG ligands, such as chemokines, and thereby altering their pattern of physiological signaling.

Its lead molecule, PA04-001, comprises a version of the pro-inflammatory chemokine interleukin-8 that carries two genetic modifications. It has been engineered to have an increased affinity for binding to GAG structures found on the surface of inflamed endothelial cells, but its G protein-coupled receptor binding site has been removed, and it is therefore unable to activate leukocytes via their CXCR1 or CXCR2 chemokine receptors. "We design the protein to bind the sugar better and turn it into a blocker," Slingsby said.

PA04-001 works by out-competing IL-8 for binding sites on the inflamed endothelium and then preventing subsequent trafficking of activated leukocytes across the endothelial layer and into the site of inflammation. "It's upstream biologically from anti-integrin approaches," Slingsby said.

Others have adopted alternative approaches to disrupting this interaction. Fremont, Calif.-based Abgenix Inc. (now part of Thousand Oaks, Calif.-based Amgen Inc.) previously had targeted IL-8 directly with a monoclonal antibody, ABX-IL8, but canceled the program following a failure of a Phase IIb clinical trial in psoriasis.

"The fact that IL-8 binds to GAGs makes it difficult for a monoclonal antibody to optimally target the protein," Slingsby said. "We believe our approach has the potential to better target proteins, which bind GAGs."

Targeting chemokine receptors with small molecules also has proved difficult. "A number of chemokine receptors have been quite difficult to target successfully with small molecules in the clinic," Slingsby said, although ChemoCentryx Inc. has achieved "some success" in that area, he added.

The Mountain View, Calif.-based firm entered a wide-ranging alliance, potentially worth $1.2 billion, with London-based GlaxoSmithKline plc last year.

Developing sugar-based drugs offers another way of disrupting the GAG-chemokine interaction, but offers less specificity than the CellJammer approach, Slingsby said. The latter, he said, "is a very direct way to target the right sugar."

PA04-001 is scheduled to enter the clinic in 2009. ProtAffin is targeting ischemic reperfusion injury following kidney transplantation initially, as that indication offers orphan drug potential, Slingsby said. It has two other development programs under way targeting undisclosed chemokine receptors and a third project outside the chemokine field.