Enterprise Therapeutics Advances a Promising New Approach for Cystic Fibrosis

Enterprise Therapeutics has reached an important milestone in its mission to improve the lives of people living with respiratory disease, announcing the publication of positive Phase 1 clinical data for ETD001 in The Journal of Cystic Fibrosis. The peer-reviewed paper highlights the safety, tolerability and favourable pharmacological profile of ETD001, a novel, long-acting inhaled epithelial sodium channel (ENaC) blocker being developed for the treatment of cystic fibrosis (CF).

The publication marks a significant step forward for Enterprise and for the CF community, reinforcing the potential of ETD001 as a differentiated therapy designed to address one of the root causes of lung disease in cystic fibrosis: impaired mucociliary clearance.

A well-tolerated, long-acting ENaC blocker

The Phase 1 study evaluated single and multiple ascending inhaled doses of ETD001 in healthy participants, at dose levels predicted to be therapeutically relevant in humans. Results showed that ETD001 was well tolerated, both as a single dose and when administered twice daily for up to 14 days. Importantly, the compound was safely administered at doses higher than those predicted to deliver long-lasting improvements in mucociliary clearance based on preclinical models.

Unlike earlier generations of inhaled ENaC blockers, ETD001 demonstrated a pharmacokinetic profile consistent with slow absorption from the lung into systemic circulation. This behaviour supports prolonged retention in the lung and the potential for an extended duration of action, key attributes for a chronic inhaled therapy intended to improve airway hydration and mucus clearance.

Another notable finding from the study was the absence of clinically meaningful effects on blood potassium levels. Because ENaC blockade in the kidney can influence potassium balance, this has been a historical concern for drugs in this class. In the Phase 1 trial, potassium levels remained within normal limits at all doses evaluated, further supporting the favourable safety profile of ETD001.

Strong alignment between preclinical and clinical data

The consistency between preclinical and clinical findings is a standout aspect of the published results. Preclinical studies had previously shown that ETD001 combines a good safety profile with sustained activity in the lung for more than 16 hours following a single inhaled dose. The Phase 1 data closely mirrored these expectations, increasing confidence in the translational robustness of Enterprise’s approach.

This strong alignment de-risks further development and underpins the company’s decision to advance ETD001 into Phase 2 clinical testing in people with cystic fibrosis.

Addressing an unmet need in cystic fibrosis

Despite major advances in CF care, significant unmet needs remain, particularly for individuals who are genetically unsuited to CFTR modulator therapies or who continue to experience progressive lung disease despite treatment. Thick, dehydrated mucus in the airways leads to impaired mucociliary clearance, recurrent infections and chronic inflammation, driving a gradual decline in lung function.

By inhibiting ENaC in the airway epithelium, ETD001 is designed to restore airway surface hydration, improve mucus clearance and ultimately support better lung function. This mechanism is complementary to existing therapies and has the potential to benefit a broad range of people with CF.

Dr Henry Danahay, Head of Biology at Enterprise Therapeutics and lead author of the publication, commented:

Momentum continues with Phase 2 underway

Building on the positive Phase 1 findings, Enterprise is currently conducting a Phase 2 clinical trial (NCT06478706) to evaluate whether 28 days of treatment with ETD001 can improve lung function in people with cystic fibrosis. Headline data from this study are anticipated in early 2026.

With cystic fibrosis affecting more than 100,000 people worldwide and an average life expectancy of around 60 years, innovation remains critical. The publication of ETD001’s Phase 1 data represents meaningful progress toward a new class of inhaled therapies aimed at improving daily respiratory health and long-term outcomes for people living with CF.

As Enterprise Therapeutics continues to advance ETD001 through clinical development, this latest milestone underscores the company’s commitment to science-driven innovation and to delivering therapies that have the potential to make a real difference for patients.