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 European Journal of Medicinal Chemistry1. The paper describes the medicinal chemistry optimisation of a new series of ENaC blockers, resulting in the invention of ETD001, Enterprise’s lead asset, a potential new inhaled treatment for cystic fibrosis (CF).
The paper, titled “Optimization of a novel series of ENaC inhibitors, leading to the selection of the long-acting inhaled clinical candidate ETD001, a potential new treatment for cystic fibrosis” is the first publication outlining the medicinal chemistry story leading to the discovery of ETD001, as well as its detailed pre-clinical profile. A potent ENaC blocker, ETD001 also has class leading low permeability through the airway epithelium, making it an optimal candidate for clinical evaluation as an inhaled treatment for people with CF (pwCF). The chemistry work described in the paper was carried out in collaboration with Evotec.
The Company commenced and is currently undergoing recruitment for a Phase 2 clinical study of ETD001 in pwCF in summer 2024, expected to complete in 2025, to understand whether 28 days of treatment will improve lung function. In September Enterprise announced that ETD001 has been granted ‘rare pediatric disease designation’ in the US by the FDA2.
Dr Steve Collingwood, Head of Chemistry, Enterprise Therapeutics, and lead author of the paper, said: “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 pwCF who are currently participating in the Phase 2 clinical trial.”
Prof Martin Gosling, CSO, Enterprise Therapeutics, commented: “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.”
CF 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. Increasing fluid volume in the lung by inhibiting ENaC with ETD001 will hydrate mucus, improve clearance, reduce mucus congestion, and is expected to drive substantial improvements in lung function. ETD001 has previously demonstrated a well-tolerated profile in healthy subjects in a Phase 1 trial and has been shown to be long-acting in pre-clinical studies3.
- https://doi.org/10.1016/j.ejmech.2024.117040
- https://enterprisetherapeutics.com/enterprise-therapeutics-granted-rare-pediatric-disease-designation-in-the-us-for-novel-cystic-fibrosis-investigational-therapy-etd001/
- https://enterprisetherapeutics.com/enterprise-therapeutics-publishes-preclinical-profile-of-etd001-a-novel-inhaled-enac-blocker/