XENEX® technology

XENEX® (xenon gas for inhalation), currently in clinical development, is an acute critical care drug therapy & device combination designed for neuroprotection in intubated patients following a hypoxic-ischemic event.  The drug is pharmaceutical grade xenon gas (99.999% pure), administered by the proprietary XENEX Delivery System (XDS).  The device uses a low-flow closed-circuit rebreathing system that automatically recaptures and recycles the gas, and precisely delivers the desired concentration over extended periods of time, making long-term neuroprotection commercially and logistically viable.  XENEX is delivered at a 50% concentration over 24 hours in the ICU.

Upon inhalation, xenon immediately crosses the blood brain barrier and enters the CNS. Its unique muti-model MoA properties address the shortcomings of previous agents: 

• NMDA Receptor Modulation: following a hypoxic-ishcemic event, there is an excessive release of nuerotransmitters, opening ion pores and allowing toxic levels of Ca+ entry.  Xenon uniquely “bathes” the NMDA receptor’s glycine site and partially modulates its ion pore. Unlike full NMDA antagonists, xenon does not completely block calcium entry—an important distinction, since physiologic glutamate signaling and modest calcium influx support neuronal survival, whereas full pore blockade can worsen apoptotic pathways. 
• Activating TREK 1 Potassium channels:  xenon prevents additional glutemate release by disrupting the neurotransmission feedback loop. TREK‑1–mediated stabilization complements xenon’s partial NMDA receptor antagonism, together preserving physiologic calcium homeostasis and reducing neuronal injury.
• Upregulating HIF 1-α gene expression: xenon markedly enhances the translational efficiency and stabilization of HIF‑1α. Once stabilized, HIF‑1α translocates to the nucleus and activates hypoxia‑response elements (HREs), driving transcription of downstream effectors such as erythropoietin (EPO) and VEGF. These HIF‑1α–dependent genes exert potent neuroprotective actions by reducing apoptosis, supporting mitochondrial function, and promoting vascular and metabolic resilience following injury. This mechanism complements xenon’s NMDA and TREK-1–mediated excitotoxicity suppression, making it a multi-modal neuroprotectant.
• Anti-Apoptotic Signaling: xenon activates pro-survival pathways (such as Bcl-2) and inhibits pro-death signals, preventing the "programmed cell death" that occurs hours after the initial injury.
• Neuroinflammation Modulation: Unlike many agents, xenon has been shown to reduce long-term neuroinflammation and microglial activation, which are key to long-term cognitive recovery.
• Mitochondrial stabilization: reducing oxidative stress and preserving cellular energy

Xenon is a near ideal agent with a demonstrated exceptional safety profile: 

• Clinical Safety: xenon has a proven clinical safety profile, with no known serious adverse events.  It has a long history of anesthetic use in humans in select EU countries, at a concentration of 70%.  Additionally, in our Phase 2 post-cardiac arrest clinical trial, at a concentration of 50%, there were no serious AEs attributed to xenon.
• Physiologic/Metabolic Safety: although xenon is biologically active, it is chemically inert. It is not associated with respiratory, hepatic, renal, or neuro toxicity.  Unlike other NMDA receptor antagonists which have been associated with significant neurotoxicity, (e.g., Olney lesions w/ ketamine).  Xenon has no bio-transformation,  protein binding, or metabolization by the liver. It is elimated through exhalation, with no hepato-renal excretion. Xenon is hemodynamically stable, which is important in critical care patients.  There are no psychomimetic effects or dissociation which are associated with other NMDA receptor antagonists.

Proprietary Integrated System

• Unique platform technology transforms any existing ICU ventilator into an XDS
• Proprietary technology developed with Rheos Medical Corp. adapted from the

              Clarity-IA®

• Controlled Closed-Loop System – XDS automatically mixes and regulates xenon & O2 delivery to the patient while safely removing CO2 & recirculating xenon 

Advantages

• Economical delivery of XENEX 
• HCP preference to utilize existing ICU ventilator (short learning-curve)
• Ease of use – intuitive, ergonomic design 
• Eliminates need for manual gas mixing 
• Minimal footprint