NOX-100

For stabilizing hemodynamic properties and improving organ function during septic shock

The Medical Need

Sepsis is a systemic inflammatory response that results in the failure of the circulation to provide blood and oxygen to vital organs of the body. Sepsis can result from a bacterial infection as well as non-infectious causes such as hemorrhagic shock, immune-mediated organ injury, ischemia, multiple trauma and tissue injury, and the administration of inflammatory cytokines during cancer chemotherapy.

Sepsis is a major unmet medical need that has no satisfactory therapeutic treatment. In the United States alone, sepsis causes the hospitalization of over 700,000 people. About 45 percent of patients with sepsis progress to septic shock, and of these, approximately 100,000 die of septic shock annually. This makes septic shock the 13th leading cause of death in the United States. In all industrialized nations, the incidence of sepsis is on the rise due to the expanding elderly population, increased number of major surgical procedures, increased use of immunosuppressive and chemotherapeutic agents, and the increased prevalence of chronic debilitating conditions.

Medinox's Approach

In the search for new therapeutic targets, NO has emerged as a key opportunity. NO's role in sepsis and septic shock is well established by many preclinical and clinical studies. NO, a potent vasodilator, is an end-product of the inflammatory sepsis cascade. Excessive NO production leads to vasodilation, vascular collapse, reduced oxygenation of tissues, and the multiple organ failure of septic shock. Because NO overproduction in sepsis can last for several days, there is a broad window in which a NO-targeted therapeutic can be effective.

Medinox is developing its NO neutralizer, NOX-100, to address the excessive NO production associated with this condition. In preclinical studies, we have demonstrated proof of concept for NOX-100 as a potential sepsis therapeutic. In animal studies, NOX-100 improved hemodynamic function, protected against organ failure, prevented bacterial translocation, and reduced mortality. Furthermore, toxicological studies show that NOX-100 has an excellent safety profile. A Phase I/IIa safety study showed that NOX-100 was safe in humans in doses up to 50 mg/kg.

Medinox is now evaluating NOX-100 in a multicenter Phase I/IIa septic shock study that will evaluate the efficacy of NOX-100 in restoring blood pressure and improving organ function of critically ill sepsis patients.