Citryll, is taking a new approach to treat autoimmune and other human diseases like lupus, vasculitis, pulmonary fibrosis, rheumatoid arthritis and organ damage due to sepsis, by targeting and inhibiting the source of auto-antigens and neutrophil extracellular trap (NET) derived toxic molecules instead of broadly targeting inflammation or acquired immunity. The latter are the MoAs of the current medicines like anti-TNF antibodies, small molecule Jak inhibitors and antagonists of B cell biology like anti-CD20 antibodies.
Citryll’s lead programme, targets the formation of neutrophil extracellular traps, called 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 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 have the potential to create game changing new treatments to prevent or treat autoimmune diseases including RA.