Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

ENOX2 levels of patients receiving NOX66 in an open label phase 1a PK Study (#267)

Ian Minns 1 , Sue Khouri 1 , Marinella Messina 1 , Graham Kelly 1
  1. Noxopharm Limited, Turramurra, NSW, Australia

NOX66, a novel investigational product containing the active ingredient idronoxil, is under investigation as a chemo- and radio-sensitizing agent across multiple therapy combinations and tumour types. The mechanism of action for idronoxil involves binding to ENOX2 – a tumour specific external membrane NADH oxidase protein. This binding leads to inhibition of the trans-membrane electron pump causing an accumulation of proton ions, leading to an increase intracellular ceramide levels and, through a cascade of downstream actions, promotes apoptosis within tumour cells. At doses administered in the NOX66 development program, it is hypothesised that idronoxil will enhance the effect of standard chemotherapy and palliative radiotherapy by preventing tumour cell repair. Pre-clinical data shows that idronoxil in combination with standard chemotherapy can significantly increase apoptosis compared with chemotherapy alone. As ENOX2 is a tumour specific cell surface protein, changes in circulating ENOX2 protein levels may act as a surrogate marker for treatment efficacy, while presence of cellular ENOX2 may act as a diagnostic marker.

Here we will present data for patients receiving NOX66 in a first in human study (NOX66-001; NCT02941523). Patients with end stage metastatic disease were allocated to receive either NOX66 once daily (400mg per day) or NOX66 twice daily (800mg per day) for 14 consecutive days. Plasma samples were collected on Day 1, Day 8 and Day 15 to measure ENOX2 levels by ELISA assay. At the time of abstract submission, 13/16 patients have commenced the study, with 8 having completed phase 1a. Phase 1a is expected to complete in September 2017, with ENOX2 levels for all patients at the two dose levels to be presented.