Citryll’s lead programme targets the formation of NETs and its pathological consequences. NETs are a part of the innate immune system. Inhibition of NET function and/or formation inhibits the release of pro-inflammatory proteins, citrullinated autoantigens as well the release of toxic histones and autoimmune complexes. Citryll’s programme does so by interfering with formation, function and clearance of NETs and NET components downstream of the protein citrullination pathway catalyzed by peptidylarginine deiminase (PAD) enzymes.
The PAD pathway is essential for the formation of NETs. tACPA binds to N-terminal citrullinated epitopes in histones that are essential for NET formation. We believe that drugs that block NET based auto-antigen production and promote the systemic clearance of NETs have the potential to create game changing new treatments to prevent or treat human diseases with high medical need like SLE, vasculitis and organ damage due to sepsis and many other indications.