New ENaC blocker demonstrates an extended duration of action

Enterprise Therapeutics have released their paper describing how, in a sheep model, low doses of their lead asset, the ENaC blocker ETD001, improved the clearance of cystic fibrosis airway mucus, demonstrating an exceptionally long duration of action.

The research suggests that ETD001, at a dose level that was well tolerated in healthy volunteer studies, offers an opportunity to assess whether a long-acting ENaC blocker can benefit patients with cystic fibrosis (pwCF). Blocking ENaC in the airways is a new approach to improve mucus clearance in pwCF, including in the over ten percent of individuals who are either intolerant to, or genetically unsuited to, CFTR modulators, which are designed to enhance production, intracellular processing, and the function of the defection CFTR protein.

Recently, numerous other ENaC blocking drugs, such as VX-371, AZD5634, BI 1265162, and QBW276 did not exhibit any benefit in clinical trials. Notably, this study offers an explanation for these failures: data from the sheep model implies that each drug may have been dosed in clinical trials at a dose too low to observe an extended duration of action on mucus clearance.

Moving forward, ETD001 is scheduled to begin a Phase II clinical study in pwCF in summer 2024, to understand whether 28 days of treatment will improve lung function. Lead author of the paper Dr Henry Danahay, Head of Biology at Enterprise Therapeutics, commented: “This data provides strong evidence that ETD001 has a superior profile compared to other inhaled ENaC blockers. Along with the results from the Phase I trials where ETD001 was well-tolerated, this study supports our high level of confidence going into the Phase II clinical trial. We remain passionate in our drive to discover novel therapies that have the potential to transform the lives of all people with cystic fibrosis.”

This study was published in the Journal of Cystic Fibrosis.