Enterprise Therapeutics’ ETD001 Shows Promise in Cystic Fibrosis Trial

Enterprise Therapeutics Ltd has published significant findings from its Phase 1 trial of ETD001, a novel inhaled epithelial sodium channel (ENaC) blocker aimed at treating cystic fibrosis (CF). The results, detailed in a peer-reviewed paper in The Journal of Cystic Fibrosis, indicate that ETD001 was well tolerated by healthy participants, even at doses higher than those required to achieve long-lasting improvements in mucociliary clearance observed in preclinical models.

The Phase 1 study assessed the safety, tolerability, and pharmacokinetics of ETD001 through both single and multiple ascending doses. Participants inhaled doses that were anticipated to be effective in humans. Findings from the trial demonstrated that ETD001 was well tolerated at both single doses and with repeated dosing twice daily for up to 14 days. Notably, the pharmacokinetic profile of ETD001 following inhalation was characterized by slow absorption into systemic circulation, indicating prolonged retention in the lungs and the potential for an extended duration of action.

In addition, the study monitored blood potassium levels, which can be affected by ENaC blockade in the kidneys. Results showed that potassium levels remained within normal limits across all evaluated doses of ETD001. This aligns with preclinical data that indicated a favorable safety profile and extended lung action lasting over 16 hours after a single inhaled dose.

Dr. Henry Danahay, Lead Author of the study and Head of Biology at Enterprise Therapeutics, expressed enthusiasm about the findings. “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,” he stated. He also acknowledged the contributions of participants in both the Phase 1 and ongoing Phase 2 trials.

Enterprise Therapeutics is currently conducting a Phase 2 trial (NCT06478706) to investigate whether 28 days of treatment with ETD001 can enhance lung function in individuals with cystic fibrosis. Headline results from this trial are expected in early 2026.

There is an urgent need for innovative therapies to address mucus obstruction in the lungs of CF patients, particularly those who are not candidates for CFTR modulators. Inhibiting ENaC in the airways of people with cystic fibrosis is anticipated to restore airway mucus hydration, potentially leading to substantial improvements in lung function.

Cystic fibrosis is estimated to affect over 100,000 people globally, with an average life expectancy of approximately 60 years. The disease is characterized by ineffective mucociliary clearance, resulting in mucus congestion, persistent infection, inflammation, and a gradual decline in lung function. Thus, the development of therapies like ETD001 could play a crucial role in enhancing the quality of life for those affected by this challenging condition.