Pipeline

ALX1

Water soluble, small molecule prodrug (<500 Da) that releases the pharmacologically active metabolite, Nitric Oxide (NO) with sustained release duration of up to 8 hours.  This candidate is formulated as a buffered aqueous solution for oral inhalation via a customized PARI eFlow® nebulizer.  The ALX1 pharmacology program includes in vitro and in vivo evidence of anti-inflammatory target engagement as well as antimicrobial efficacy against P. aeruginosa and Non-tuberculous mycobacterium infections.

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.