Noxopharm White Paper

9 Disclaimer: Veyonda is currently not approved in Australia or any other country Veyonda® – DARRT program The NOX clinical trial program provides a pipeline of indications designed to maximise the value of Veyonda while de-risking the portfolio. DARRT: Direct and Abscopal Response to RadioTherapy DARRT aims: • To combine Veyonda with low-dose radiotherapy (RT) in order to trigger an immune/ inflammatory response in a single tumour, with that response then spreading systemically, resulting in a widespread anti-cancer response known as an abscopal response. • The aim is to achieve an anti-cancer response ranging from preventing tumour growth (stable disease) through to tumour shrinkage or resolution (partial or complete responses). DARRT rationale: • DARRT is based on the use of low-dose radiation to damage and inflame a tumour, rather than to deliver a killing effect intended to kill all cancer cells, which also results in damage to off-target cells including resident immune cells. • Low-dose RT damages both nuclear andmitochondrial DNA, which the cancer cells then attempt to repair; in the case of nuclear DNA, repair is by a range of specialist repair enzymes and in the case of mitochondrial DNA, by the process of autophagy (self-digestion). • Damage to mitochondrial DNA triggers the release of cytokines and interferons, in the irradiated tumour which enter the bloodstream and trigger immune responses in distant lesions. • Blocking autophagy, thereby allowing the damaged mitochondrial DNA to remain in situ, maximising the production of interferons and maximising the chance of triggering an abscopal response. • By inhibiting S1P, Veyonda blocks both repair processes, with inhibition of autophagy believed to be key to the triggering of an abscopal response. DARRT Program objectives: To demonstrate that in metastatic solid tumours: • Veyonda is safe and well-tolerated when combined with low-dose radiotherapy (RT). • Veyonda plus low-dose RT results in improved outcomes versus radiotherapy alone in a range of solid cancers.