Breakthrough trial offers new hope for cystic fibrosis patients

Enterprise Therapeutics Ltd, a biopharmaceutical company focused on developing innovative therapies for respiratory diseases, has announced the publication of a peer-reviewed study in the European Journal of Medicinal Chemistry. The study details the medicinal chemistry process that resulted in the development of ETD001, a promising new inhaled ENaC blocker for cystic fibrosis (CF).

This paper presents the extensive work that culminated in the selection of ETD001 as a lead candidate. This ENaC blocker has demonstrated a potent effect in preclinical models, with the added advantage of low permeability through the airway epithelium. This profile makes it an ideal inhaled therapy for people with cystic fibrosis.

The research, conducted in collaboration with Evotec, outlines how the optimisation of the compound led to ETD001’s unique properties, positioning it as a potential game-changer for CF treatment.

A step closer to clinical impact

Enterprise Therapeutics initiated a Phase 2 clinical trial of ETD001 in people with cystic fibrosis in July 2024. The study, which aims to assess the effect of 28 days of treatment on lung function, is currently recruiting participants and is expected to be completed in 2025. In recognition of ETD001’s potential, the FDA granted the drug ‘rare paediatric disease designation’ in 2024.

Dr Steve Collingwood, head of chemistry at Enterprise Therapeutics and lead author of the study, commented, “We are proud of our inhaled medicinal chemistry strategy, the success of which is evidenced by the superior profile of ETD001 compared to other inhaled ENaC blockers. We are grateful to our team of scientists for supporting the development to this stage, and to the people with CF who are currently participating in the Phase 2 clinical trial.”

Exciting prospects for CF treatment

Enterprise’s Chief Scientific Officer, Prof Martin Gosling, emphasised the broader potential of ETD001 in cystic fibrosis treatment, “the publication of this paper in a leading peer-reviewed medicinal chemistry journal is testament to the great science performed by the chemistry teams at Enterprise and Evotec. We firmly believe that the unique properties of ETD001, giving rise to class-leading lung retention, will deliver an effective therapy to people with CF currently unable to benefit from CFTR modulators. We look forward to sharing the results of our Phase 2 study in 2025.”

Cystic fibrosis affects over 100,000 people globally, and ETD001 could represent a significant advancement in CF therapy. By inhibiting the epithelial sodium channel (ENaC), ETD001 helps hydrate mucus, improve clearance, and reduce congestion in the lungs, leading to improved lung function. The drug has already demonstrated a favourable safety profile in Phase 1 trials and shown long-acting potential in preclinical studies.

Next steps

As the Phase 2 study progresses, Enterprise Therapeutics remains focused on validating ETD001’s efficacy and safety in people with cystic fibrosis. The company is excited to continue its work and looks forward to the future of this promising therapy.

This study was published in the European Journal of Medicinal Chemistry.