Noxopharm White Paper

1 Disclaimer: Veyonda is currently not approved in Australia or any other country Veyonda® – the basics Idronoxil (dehydroequol) is the active ingredient in Veyonda . It is a synthetic small molecule first described in 1992 and subsequently celebrated for its unique blend of anti-cancer and anti-inflammatory functions, with good tolerability in patients, and a robust safety profile. Since then, its reputation as a potentially important new anti-cancer drug prospect has grown based on it being a multi-functional drug working via a number of different anti-cancer mechanisms. For a disease as complex as cancer where the cancer cell has a wide range of options at its disposal to avoid detection and to override bodily controls, the more of those functions that can be blocked, the better the outcome is likely to be for the patient. Initially, idronoxil was regarded as having classic anti-cancer functions (known as oncotoxic functions). These include direct killing of the cancer cell via apoptosis, blocking the cancer cell from dividing, or blocking repair mechanisms that render the cell more susceptible to damage from chemotherapies and radiotherapy. However, recent studies have revealed two other sides to this drug: (i) an ability to restore immune responses against cancer cells (known as immuno-oncology functions ); and (ii) an ability to block excessive immune and inflammatory responses used by cancers to grow and spread, and triggered by tissue damage caused by viral infections (known as anti-inflammatory functions ). We now understand that the overall anti-cancer function of the drug is the result of a mix of all three functions - oncotoxic, anti-inflammatory and immuno-oncology - with the evidence increasingly pointing to the latter as being a key anti-cancer function. Combined with the growing evidence for a hyper-immune/inflammatory response being behind septic shock, including many deaths from COVID-19 disease, Veyonda also has emerged as a potential treatment of disabling symptoms and death from septic shock. Veyonda is the final dosage form. It contains idronoxil in a proprietary fatty base that is delivered as a suppository. A suppository dosage form is an important key to the drug’s success. Absorption of idronoxil from the lower rectum is via the inferior haemorrhoidal vein, thereby avoiding the portal circulation and first-pass liver metabolism. Second-pass liver metabolism produces a specific Phase 2 metabolite profile achieved with intravenous and rectal dosing, but not oral dosing. A suppository dosage form is a practical (self-medication) and cost-effective (outpatient treatment) alternative to intravenous infusion, offering the ability to maintain steady-state drug levels for treatment cycles up to 14 days. Sustained steady-state levels of certain Phase 2 idronoxil metabolites are fundamental to the drug’s success.