ProtAffin has been awarded €2.7 million (about $3.8 million) in funding by Austria’s public funding body for translation research (FFG) to support preclinical development of its lead anti-inflammatory candidate PA401 against respiratory diseases, and particularly chronic obstructive pulmonary disease (COPD). The firm says it will likely commence Phase I clinical development with PA401 during early 2012.
ProtAffin is exploiting its CellJammer®discovery technology to generate a pipeline of glycan-binding decoy proteins for applications in respiratory medicine, inflammation, and oncology. The initial focus is on chemokines for chronic and acute inflammatory conditions, and on the clinical validation of glycan-binding decoy proteins for inflammation in respiratory medicine.
Lead product PA401 is a glycan-binding decoy protein based on interleukin-8 (IL-8). The candidate has been developed using the CellJammer technology to modify wild-type human IL-8 (CXCL8) so that it acts as a targeted anti-inflammatory product, the firm explains. It claims the final PA401 candidate displays a novel mechanism of action and has demonstrated highly improved binding affinity to glycans driving inflammatory processes, as well as impaired binding to CXCR1 and CXCR2, the GPCR receptors for IL-8 found on human neutrophils. PA401 has in addition shown high efficacy in a number of preclinical efficacy models of chronic and acute lung inflammation. The candidate can be cost-effectively manufactured by E.coli fermentation, ProtAffin adds.
The CellJammer technology involves first selecting a protein target and identifying the nature of its protein-glycan interactions, which are analyzed using specific databases and algorithms. The glycosaminoglycan (GAG) binding affinity of the protein is then increased by modifying selected amino acids to create a decoy protein, which blocks interaction between the unmodified protein and its GAG ligand. The bioactive domain of the target protein is also disabled. For a chemokine target, for example, this may be the GPCR binding domain. ProtAffin claims the validity of the CellJammer approach has already been demonstrated for five distinct target proteins.
The firm’s preclinical pipeline is headed by PA401. In July ProtAffin signed a manufacturing contract for the candidate with CMC Biologics’ Danish operations. The contract covers the manufacture and supply of PA401 for preclinical development and early clinical development in COPD and related respiratory indications.
ProtAffin’s preclinical pipeline includes a number of earlier-stage candidates. An MCP-1 program is at the research-stage for the potential treatment of multiple sclerosis and cardiovascular indications. The program comprises glycan-binding decoy proteins based on the human monocyte chemotactic protein 1 (MCP-1), a glycan-binding CC-chemokine that binds to the GPCR receptor CCR2 expressed on monocytes and macrophages.
Candidate selection is separately under way for an SDF-1α program targeting autoimmune, inflammatory, and antimetastatic indications. SDF-1α binds to receptor CXCR4 expressed on a number of cell types. The firm has developed a lead series of SDF-1α-based glycan-binding decoy proteins that appear to show superior GAG binding compared with the wild-type protein.
Protaffin is in addition working on an anti-angiogenesis program for oncology, which is currently at the discovery stage.