The complement cascade is the backbone of our innate immune system. However, over activation or insufficient regulation of this powerful system is implicated in the pathologies of a wide variety of conditions for which adequate therapy is urgently required.


The Complement System

The complement system is the body’s most important innate immune protector and consists of more than 30 proteins that must work together like clockwork.  Read more

Role in Disease

Over activation or insufficient regulation of this powerful system is implicated in the pathologies of a wide variety of conditions.  Read more

Novel Drug Targets

Our drug candidates inhibit the complement cascade by targeting C9 and Factor D.  Our lead drug candidate is orally available and holds promise to become one of the most wide spectrum agents ever developed.  Read more


 

The basic science behind our drug candidates is described in the following papers. Copies can be made available upon request.

  • Lee M, Guo J-P, Schwab C, McGeer EG, McGeer PL. Selective inhibition of the membrane attack complex of complement by low molecular weight components of the aurin tricarboxylic acid synthetic complex. Neurobiol Aging 2012; 33: 2237-2246. doi:10.1016/jneurobiolaging.2011.12.005

This paper describes the discovery of agents that will block formation of the membrane attack complex (MAC) in vitro and in vivo by binding to C9.

  • Lee M, Guo J-P, McGeer EG, McGeer PL. Aurin tricarboxylic acid self-protects by inhibiting aberrant complement activation at the C3 convertase and C9 binding stages.  Neurobiol Aging 2013; 34: 1451-1461.

This paper describes the mechanism of action of our prototype drugs, which bind to C9 and Factor D, inhibiting the alternative pathway at the C3 convertase stage as well as the C9 stage of MAC formation

  • Lee M, McGeer PL. Aurin tricarboxylic acid protects against red blood cell hemolysis in patients with paroxysmal nocturnal hemoglobinemia. PLOS ONE 2014: 9 e87316. Doi 1371/journal.pone 0083716.  (View URL, Access full-text PDF)

This paper describes how our prototype agents can act to block the capacity of serum from PNH patients to hemolyze their red blood cells (RBCs), thus establishing them as potential treatments for PNH.

Review articles have been published that discuss the complement system and its role in disease. The following can be recommended for background information.

  • Daniel Ricklin and John D Lambris. Complement-targeted therapeutics. Nature Biotechnology 25 2007, 1265 – 1275. doi:10.1038/nbt1342. (View URL, Access full-text PDF)
  • Ehrnthaller C, Ignatius A, Gebhard F, Huber-Lang M. New insights of an old defense system: structure, function, and clinical relevance of the complement system. Mol Med. 2011 Mar-Apr;17(3-4):317–329.  (View URL, Access full-text PDF)

 

Dr. McGeer has prepared a brief lecture for those interested in learning more about the complement system’s role in various diseases and the discoveries that led him to found Aurin Biotech. Click here to view the presentation.