This inhaled treatment, in the second phase of its study, could help patients who do not benefit from CFTR modulators
Pharmaceutical company Enterprise Therapeutics has published a peer-reviewed paper describing the medicinal chemistry optimisation of a new series of ENaC blockers to treat cystic fibrosis.
The inhaled treatment ETD001 is a potent ENaC blocker with low permeability through the airway epithelium, making it a good candidate for clinical evaluation as an inhaled treatment for people with cystic fibrosis.
“We firmly believe that the unique properties of ETD001, giving rise to class-leading lung retention, will deliver an effective therapy to people with cystic fibrosis currently unable to benefit from CFTR modulators,” said Enterprise Therapeutics CSO professor Martin Gosling.
Cystic fibrosis is a genetic condition that impacts how salt and water move in and out of cells. It is characterised by recurrent infections and the accumulation of mucus in the body’s passageways, such as the lungs.
While CFTR modulator therapies can correct the malfunctioning gene that causes this, the therapy is only effective for those with specific mutations.
However, phase one of the ETD001 study has shown that healthy subjects tolerate ETD001 well, and pre-clinical studies found it to be long-acting.
Increasing fluid volume in the lung by inhibiting epithelial sodium channel (ENaC) can hydrate mucus, reduce congestion and improve overall lung function.
Recruitment for phase two of the clinical study has begun, with the aim of understanding if 28 days of treatment will improve lung function. This phase is expected to finish next year.
“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,” said the paper’s author and Enterprise Therapeutics head of chemistry Dr Steve Collingwood.
“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.”
In September, ETD001 was granted ‘rare pediatric disease designation’ in the US by the FDA.
This is the first publication highlighting the medicinal chemistry story leading to the discovery of ETD001 and its pre-clinical profile.
The paper is titled “Optimisation 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”.
The chemistry work of this study was conducted with biotechnology company Evotec.
