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Graft rejection

Complement 3 (C3); C5a

Mouse studies suggest a combination of C3 and C5a inhibition could be useful for preventing graft rejection. In a mouse model for tracheal transplant, C3 knockout animals treated with NOX-D19, an aptamer antagonist of C5a, had decreased thrombin activation, vascular abnormalities and fibrosis and increased oxygenation and blood perfusion to engrafted tissue compared with wild-type or untreated controls. Next steps could include preclinical optimization of C3 and C5a inhibitors.
Noxxon Pharma AG's NOX-D19 is in preclinical development for liver and kidney failure.
AstraZeneca plc's MEDI-7841, a mAb against C5a and C5, is in Phase I testing for chronic obstructive pulmonary disease (COPD).
Novo Nordisk A/S's anti-C5aR-151 (NN8209), an anti-C5a mAb, is in Phase I testing for rheumatoid arthritis (RA).
Potentia Pharmaceuticals Inc. and partner Novartis AG are developing compstatin (APL-1; POT-4), a C3 inhibitor that is in Phase II testing for age-related macular degeneration (AMD).

SciBX 6(18); doi:10.1038/scibx.2013.443
Published online May 9, 2013

NOX-D19 is patented by Noxxon Pharma; licensing status undisclosed

Khan, M.A. et al. Proc. Natl. Acad. Sci. USA; published online March 25, 2013;
Contact: Mark R. Nicolls, Stanford University School of Medicine,
Stanford, Calif.