Cystic fibrosis - MOLI-1901

Cystic fibrosis is a debilitating and fatal disease, which is caused by a genetic mutation of the instrumental protein cystic fibrosis transmembrane regulator (CFTR).

This protein is involved in moving salt and water to the surface of the linings of the lungs, providing hydration and facilitating the cleansing of the lung's surface.

In healthy people, the protein acts as an ion-specific channel, but in CF patients, there is a defect in this protein channel that results in poorly hydrated, thickened mucus secretions in the airways, and consequently severely impaired mucociliary flow because of the impaired clearance. Chronic secondary infections frequently occur, resulting in progressive lung damage and deterioration.

Current therapies for CF are able to target only its symptoms. A new treatment is being developed by Lantibio in collaboration with AOP Orphan. MOLI-1901 is a cyclic polypeptide designed to open an alternate salt channel in normal and diseased lungs, with the aim of improving the hydration of mucus in the lungs, hence normalising the mucus and preventing its retention, as well as avoiding the normal inflammation and bacterial infections CF patients are prone to.

A randomised single blind placebo controlled Phase I clinical trial was carried out in four adults with CF and four healthy volunteers.¹ Up to 10µmol/l of the active and vehicle were given to the subjects intranasally, and the nasal potential difference was measured with a high impedance voltimeter at baseline and after each dose.

The drug significantly increased chloride transport compared with placebo vehicle in both groups, and no drug related adverse events were observed. Phase II trials are being carried out.