This page contains Forward Looking Statements made as of October 19, 2016.*
AIR001 is a sodium nitrite solution for intermittent inhalation via nebulizer. Nitrite is a direct vasodilator and can be recycled in vivo to form nitric oxide (NO) independent of the classical NO synthase (NOS) pathway. Nitrite mediated NO formation has several beneficial effects, including dilation of blood vessels and reduction of inflammation and undesirable cell growth. Generation of NO from sodium nitrite is not dependent upon endothelial function and is enhanced in the setting of tissue hypoxia and acidosis, conditions in which NOS activity typically is depressed.
What is AIR001 and How Does it Work?
AIR001 Inhalation Solution is sodium nitrite formulated with a phosphate buffer into an inhalation solution. Nitrite is a physiological signaling molecule with roles in intravascular endocrine nitric oxide (NO) production, hypoxic vasodilation, signaling, and cytoprotection after ischemia-reperfusion. Nitrite serves as the largest physiologic reservoir of NO and can be converted to NO independent of NO synthase (NOS) activity.
In experimental models, nitrite use demonstrated improved remodeling both in the pulmonary vasculature and right ventricle. Hemodynamic effects include venodilation with reductions in right atrial pressures, pulmonary and systemic vasodilation with reductions in pulmonary vascular resistance and left atrial pressures, and improved cardiac relaxation. In addition, recent clinical and nonclinical studies have demonstrated that nitrite can stimulate mitochondrial biogenesis and mitochondrial fusion and decrease mitochondrial oxygen consumption through a mechanism distinct from that of NO, which may have utility in treating heart failure.
In early clinical studies, AIR001 demonstrated positive hemodynamic effects with reductions observed in right atrial pressure and pulmonary capillary wedge pressure, as well as improvements in mean pulmonary artery pressures and cardiac output.
AIR001 Development Status
We are developing AIR001 for treatment of heart failure with preserved ejection fraction (HFpEF), a condition that affects millions in the U.S. and for which no proven therapeutic agent is available. We are supporting two institution-sponsored phase 2a studies in patients with HFpEF to evaluate acute hemodynamic effects of AIR001 and to evaluate its acute effects versus placebo on submaximal oxygen consumption and exercise hemodynamics. If the results from these phase 2a studies are positive we would plan to initiate a phase 2b proof-of-concept study in HFpEF patients.
AIR001 has also been selected by the Heart Failure Clinical Research Network (HFN) for evaluation in a 100-patient, multicenter, randomized, double-blind, placebo-controlled, Phase 2 clinical trial known as the Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF (INDIE-HFpEF) study. The HFN is made up of premier clinical centers located across North America and was established to expedite clinical research on treatments and strategies to improve the management of acute and chronic heart failure. The HFN is providing the platform to conduct the INDIE-HFpEF study. Mast will provide test materials, nebulizers, and regulatory, technical, and additional financial support.