Enterprise Therapeutics publishes results of Phase 1 study of ETD001, a novel inhaled ENaC blocker for treatment of Cystic Fibrosis, in The Journal of Cystic Fibrosis

Enterprise Therapeutics Ltd (Enterprise), a biopharmaceutical company dedicated to the discovery and development of novel therapies to improve the lives of people with respiratory diseases, today announced the publication of a peer reviewed study in The Journal of Cystic Fibrsosis. The paper, titled 'ETD001, a long-acting inhaled ENaC blocker, is well tolerated in a first human, healthy participant trial', describes the results of the Phase 1 trial of Enterprise's novel epithelial sodium channel (ENaC) blocker, ETD001, indicating that ETD001 is well tolerated in healthy individuals at higher doses than required to observe long-lasting improvements in mucociliary clearance in preclinical models.

The Phase 1 study to evaluate the safety, tolerability and pharmacokinetics of ETD001 followed single and multiple inhaled ascending doses, at levels predicted to be efficacious in humans. The results from the trial show that ETD001 was well tolerated at single doses and on repeat dosing twice daily, for up to 14 days. Unlike historical inhaled ENaC blockers, the pharmacokinetic profile of ETD001 following inhaled dosing was consistent with slow absorption out of the lung and into the systemic circulation, consistent with prolonged retention in the lung and the potential for extended duration of action. Furthermore, target-mediated ENaC blockade in the kidney can lead to changes in blood potassium levels. This trial demonstrated that levels of blood potassium remained within normal limits at all doses of ETD001 evaluated.

These results align exceptionally well with the pre-clinical data, which demonstrated a good safety profile and an extended duration of action in the lung for >16 hours after a single inhaled dose. Enterprise is currently conducting a Phase 2 trial (NCT06478706) investigating whether 28 days of treatment with ETD001 improves lung function in people with cystic fibrosis, with headline data expected in early 2026.

There is an urgent need for new therapies to treat mucus obstruction in the lungs of people with CF, and especially those who are genetically unsuited to CFTR modulators. We are passionate about working towards treatments that will benefit all people with cystic fibrosis and are excited to publish these promising results from our Phase 1 trial. We are grateful for everyone who took part in this trial, and for the people with cystic fibrosis that are enrolled in the ongoing Phase 2 trial of ETD001."

Dr Henry Danahay, Lead Author of the Paper and Head of Biology, Enterprise Therapeutics

Cystic fibrosis is estimated to affect over 100,000 people worldwide, with an average life expectancy of ~60 years. Failed mucociliary clearance and mucus congestion in the lungs leads to cycles of infection and inflammation and an ongoing decline in lung function. Inhibition of ENaC in the airways of people with cystic fibrosis represents an approach to restore airway mucus hydration and is expected to drive substantial improvements in lung function.