N30 Pharmaceuticals, Inc., a leader in the development of therapeutics that target S-nitrosoglutathione reductase (GSNOR), has administered the first dose in its phase Ib/ IIa clinical trial of N6022 in patients with cystic fibrosis (CF). The study is a multi-centre, double-blind, randomized, placebo-controlled evaluation of ascending doses of N6022 in patients who have two copies of the F508del-CFTR mutation, the most common and serious form of CF.

The clinical study is conducted in collaboration with the Cystic Fibrosis Foundation’s Therapeutics Development Network (TDN). Scott Donaldson, MD, at The University of North Carolina, Chapel Hill is the lead principal investigator for the study. The first patient was dosed this week at National Jewish Health in Denver.

The primary objective of the study is to evaluate the safety of repeat doses of N6022. Secondary and exploratory objectives include the evaluation of N6022 serum levels, lung function, and other markers of disease activity in CF.

“We are indebted to the cystic fibrosis clinicians and nurses who have given us such valuable advice, to the members of the TDN who have been instrumental in getting this first trial started, and to the patients who will be volunteering for participation. With this first trial, we look forward to paving the way to a new class of therapy for cystic fibrosis,” said Charles Scoggin, MD, president and chief executive officer of N30 Pharma.

Cystic fibrosis is the most common, life-threatening, genetic disease of Caucasians. It is characterized by a defect in the chloride channel of human cells. This channel, known as the “cystic fibrosis transmembrane conductance regulator”, or CFTR, is critical for adequate water coating, or “hydration” in airways and other organs of the body. As a consequence of a mutation in the gene for CFTR, F508del-CFTR, patients produce a form of CFTR that is broken down and discarded in the cells of the body. N30 Pharma’s new drugs aim to rescue the damaged CFTR, decrease inflammation, and restore proper hydration to critical organs, particularly the lung.

N6022 is the first of a novel class of N30 Pharma’s drugs aimed at conservation of Snitrosoglutathione (GSNO) a key, endogenous, signaling molecule that has been shown to be reduced in cystic fibrosis patients.  N30 Pharma’s drugs restore GSNO levels by inhibiting GSNOR, the enzyme in the body that breaks down GSNO.

N30 Pharma’s GSNOR inhibitors have dual effects in cystic fibrosis. First, in experimental models of cystic fibrosis, they rescue or “correct” the abnormal chloride channel function that causes the thick, tenacious secretions of the lung and other organs characteristic of cystic fibrosis. Secondly, they are potently anti-inflammatory. This is potentially important because inflammation, particularly of the lung, is the cause of major morbidity in CF patients.

N30 Pharma is the first company to discover and develop small molecules targeting GSNOR.