Technology

Xenon

NP’s intellectual property is comprised of a suite of patents around the method of use and delivery of Xenon.

PHARMACEUTICAL GRADE XENON

  • What is Xenon?
    • Xenon, a Greek word meaning “rare,” is one of six noble gases
    • Xenon (symbol: Xe) has been used in the Medical Community for diagnostic and treatment purposes for more than 60 years as an anesthetic
  • Landmark Discovery that Xenon is a potent N-Methyl-D-aspartic acid (NMDA) antagonist with neuroprotective properties – Franks, Nature, 1998
  • Xenon’s multiple mechanisms of action and synergy with therapeutic hypothermia, or targeted temperature management, have been demonstrated to protect against neurologic injury in preclinical models.³
    • Anti-Excitotoxicity – Anti-NMDA properties prevent excessive entry of calcium, a precursor to cell death early following several forms of acute neurological injury
    • Anti-Neuroapoptosis – Reduces expression of genes associated with programmed cell death (apoptosis) & increases anti-apoptotic proteins after neuronal injury
    • Cytotoprotective – Upregulates the reparative & restorative responses to oxygen deprivation even under normoxic conditions
    • Synergy with therapeutic hyperthermia, or cooling
    • Cardioprotective properties have been demonstrated in preclinical trials
    • Others
  • Clinical Evidence – Results from a Phase II Superiority Study published in JAMA in March 2016 showed statistically significantly less brain damage and directionally positive survival outcomes (though the study was not statistically powered to show such differences in this secondary endpoint) between a xenon plus cooling group versus a cooling-alone group.
    • Less Brain Damage: an MRI neuroimaging technique (Diffusion Tensor Imaging) to visualize location, orientation, & anisotropy (differences in diffusion) of brain’s white matter tracts revealed the following:
      • Over 50% less damage in the Xenon group was observed in context to those patients who survived or expired:
        • Fiber density (microintegrity), P = 0.006, of the white matter in the brain; and,
        • Nerve fiber protective covering in the brain (demyelination), P = 0.04
      • Overall, 41.7% of voxels of white matter tracts measured had less damage
      • Treatment effect size of xenon on the MRI biomarker was more than 50% of the difference in the measure observed between survivors and those who died
      • This MRI biomarker exhibited the best independent predictive value for mortality during the 6-month follow-up period
    • Improved Survival: The Phase II Study (N=110) was not statistically powered to show survival. However, a directionally positive absolute improvement in survival of 7.3% was observed in the intention-to-treat population, P = 0.053
      • A post-hoc analysis of patients with return of spontaneous circulation (ROSC) within 30 minutes, ~90% of all patients in the Study, revealed a statistically significant absolute improvement in survival of 12.3% (relative differences higher). This will serve as the basis for the patient inclusion criteria in the planned Phase III Study.
  • Non-toxic: no accumulation (elimination by exhalation); not metabolized

XENON DELIVERY DEVICE

Xenon is a rare noble gas and is therefore delivered using a patented closed-loop inhalation system: gas controller (50% Xe + 50% O2), consumable circuit, ventilator, and monitors.

Note: a 12+ year exclusive agreement with Praxair, Inc (PX), 1 of only 2 known cGMP pharmaceutical grade Xenon supplier, is in place.

 

³ Maze, Can J Anesth/J Can Anesth. DOI 10.1007/s12630-015-0507-8