Nitric Oxide Prodrugs

Nitric oxide produced in higher concentrations has a critical anti-inflammatory effect by serving as a checkpoint inhibitor of the NLRP3 inflammasome.  Decreasing production of IL-1b and recruitment of neutrophils, accelerating the rate of clearance in tissue macrophages, downstream reductions in IL-17, and decreased E-selection expression on endothelial cells limiting leukocyte recruitment are some of the other known anti-inflammatory mechanisms of nitric oxide which could be beneficial to patients. 

As an antimicrobial, nitric oxide is a unique alternative to chronic antibiotics because it has broad-spectrum activity. Nitric oxide kills bacteria via multiple mechanisms including nitrosative and oxidative stresses that damage DNA, lipid membranes, proteins, and iron-sulfur clusters leading to an extremely low propensity for drug resistance.

Vast is developing nitric oxide prodrugs that can utilize this dual mechanism of action in inhaled form using dry powder inhalers, meter dose inhalers, or aerosolized solution formulations to target a broad range of severe respiratory infections.  Once deposited in the lungs, the prodrugs begin to degrade with total nitric oxide release durations ranging from 1 to 24 hours depending on the specific chemistry.  

The company has a broad, worldwide patent portfolio including issued patents and pending applications at the composition of matter, methods of manufacture, formulation science, and adjuvant therapy levels of our strategy.  The issued patents cover ALX1, nitric oxide-releasing compounds, and their pharmaceutical formulations.  

Manuscripts published by Founder and Chief Scientific Officer, Dr. Mark Schoenfisch are listed below.