Noxopharm White Paper

7 Disclaimer: Veyonda is currently not approved in Australia or any other country STING and septic shock In some circumstances, the initially protective inflammatory response triggered by STING tips over into a toxic, hyperacute inflammatory response (known as cytokine release syndrome or ‘cytokine storm’ ) associated with an abnormally excessive immune response, eventually evolving towards the onset of septic shock. This inappropriate response creates generalised tissue injury through reduced blood flow (from blood-clotting) and exposure to inflammatory cytokines, leading to further STING activation in damaged tissues. Recent evidence suggests that the STING pathway is a key player in this “sterile” inflammatory response to damaged tissue such as seen in acute kidney injury, ischemic cardiac cell death, acute pancreatitis, radiation-induced liver injury, or silica-induced lung inflammation. STING and idronoxil Idronoxil is a strong inhibitor of STING signaling. Through this inhibitory effect on the STING pathway, idronoxil has the potential to block the production of a broad range of cytokines including type I interferons (IFN- β ) and pro-inflammatory cytokines such as IL-6 and TNF- α . In vitro studies show that idronoxil significantly lowers levels of IL-6 and interferons by its inhibitory effect on the STING pathway. Idronoxil inhibition of STING also has been shown in both virally-infected human fibroblasts and non-virally infected human cancer cells. STING inhibitor idronoxil (IDX) to treat sepsis IL-1, IL-6, IL-12, IL8, TNF-α cytokine production Interferon production STING Cytoplasm Nucleus cGAS NF- κ B pathway IRF3 pathway Acute inflammation /immune response leading to sepsis STING inhibitor Idronoxil (IDX) to treat sepsis Self DNA Tissue damage upon acute inflammation IDX IDX has recently been established as a potent STING inhibitor through joint research conducted by Noxopharm Ltd and the Centre for Innate Immunity and Infectious Disease at the Hudson Institute. IDX switches off STING’s capacity to produce chemokines and cytokines upon detection of DNA released after tissue damage, stopping it from triggering an acute immunological response that would lead to sepsis. IDX is a clinically ready, small molecule with FDA IND approval with a unique opportunity to help these SARS-COV2 infected patients with severe inflammation symptoms and prevent or reduce Sepsis.