ENaC

The US Food and Drug Administration (FDA) has granted rare paediatric disease (RPD) designation to Enterprise Therapeutics’ investigational cystic fibrosis therapy. Estimated to affect more than 100,000 people globally, cystic fibrosis is a genetic disease that causes sticky mucus to build up in the lungs, digestive system and other organs in the body. Symptoms usually begin in early childhood and vary between patients, but the condition gets progressively worse over time and causes increasing damage to the affected organs. Enterprise’s ETD001, which targets the sodium channel in the airway epithelium to increase the hydration and clearance of mucus, has already demonstrated a well-tolerated profile in a phase 1 trial of healthy participants and has been shown to be long-acting in pre-clinical studies. A phase 2a trial is now aiming to assess the safety and efficacy of the candidate in patients who are ineligible for, or are not receiving, cystic fibrosis transmembrane conductance regulator modulator therapy. FDA RPD designation aims to incentivise drug development for serious or life-threatening diseases that affect fewer than 200,000 people in the US and primarily impact patients aged under 18 years. Under the programme, a sponsor that receives an approval for a RPD product may qualify for a priority review voucher (PRV) that can be redeemed to expedite the review of a different product, or be sold or transferred to another sponsor. John Ford, Enterprise’s chief executive officer, said: “As we progress through our phase 2a trial of ETD001, this RPD designation will further support our mission to advance this novel approach for treating people with cystic fibrosis with the highest unmet medical need, as rapidly as possible.” Annabella Amatulli, head of regulatory affairs at the company, added: “The RPD designation will give Enterprise access to valuable incentives and support from the FDA during the development of ETD001, including the eligibility to request a PRV at the time of marketing approval.” The FDA’s decision comes just two months after Enterprise announced that the first cystic fibrosis patient had been dosed in its phase 2a trial, which Ford said represented “an incredible milestone”.

BRIGHTON, England--( BUSINESS WIRE )--Enterprise Therapeutics Ltd (Enterprise), a biopharmaceutical company dedicated to the discovery and development of novel therapies to improve the lives of those suffering from respiratory disease, today announced its novel cystic fibrosis (CF) investigational therapy, ETD001, has been granted ‘rare pediatric disease designation’ (RPD) in the US by the Food and Drug Administration (FDA). 1 ETD001 is a low molecular weight compound with first-in-class potential, which targets the sodium channel (ENaC) in the airway epithelium to increase the hydration and clearance of mucus. Enterprise announced dosing of the first person with cystic fibrosis (pwCF) in its Phase 2a trial of ETD001 on 23 rd July 2024 2 . The trial aims to deliver clinical proof-of-concept and to assess the safety and efficacy of ETD001 in the ~10% of pwCF with the highest unmet medical need. The study will assess lung function (FEV1) in pwCF who are either ineligible for or are not receiving CFTR modulator therapy. The RPD designation was based on the assessment of CF as a serious or life-threatening disease, primarily affecting individuals aged from birth to 18 years. CF is estimated to affect over 100,000 people worldwide, with an average life expectancy of only 50 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 studies 3 . Dr John Ford, CEO, Enterprise Therapeutics, said: “We’re delighted with the FDA’s decision and would like to thank the Office of Pediatric Therapeutics and the Office of Orphan Products Development for their consideration. As we progress though our Phase 2a trial of ETD001, this RPD designation will further support our mission to advance this novel approach for treating pwCF with the highest unmet medical need, as rapidly as possible.” Annabella Amatulli, Head of Regulatory Affairs, commented: “We are thrilled to be granted the RPD designation by the FDA, a regulatory framework intended to encourage and accelerate innovative therapies, in recognition of the significance of our programme in addressing an unmet medical need. The RPD designation will give Enterprise access to valuable incentives and support from the FDA during the development of ETD001, including the eligibility to request a Priority Review Voucher (PRV) at the time of marketing approval.” https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions https://enterprisetherapeutics.com/enterprise-therapeutics-doses-first-person-with-cystic-fibrosis-in-phase-2-trial-for-novel-therapy-etd001/ https://enterprisetherapeutics.com/enterprise-therapeutics-publishes-preclinical-profile-of-etd001-a-novel-inhaled-enac-blocker/

BRIGHTON, UK I July 23, 2024 I Enterprise Therapeutics Ltd (Enterprise), a biopharmaceutical company dedicated to the discovery and development of novel therapies to improve the lives of those suffering from respiratory disease, today announced dosing of the first person with cystic fibrosis (pwCF) in its Phase 2a trial of ETD001. ETD001, a low molecular weight compound with first-in-class potential, targets the epithelial sodium channel (ENaC) in the airway epithelium to increase the hydration and clearance of mucus. The Phase 2a trial aims to deliver clinical proof-of-concept and to assess the safety profile of ETD001 in the 10% of pwCF with the highest unmet medical need. The study will be performed at sites located in the UK, Germany, France and Italy and will assess lung function (FEV1) in pwCF who are either ineligible for or are not receiving CFTR modulators. CF is estimated to affect over 100,000 people worldwide, with an average life expectancy of only 50 years. Failed mucociliary clearance and mucus congestion in the lungs of pwCF 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 strong safety profile in healthy participants in a Phase 1 trial and has been shown to be long-acting in pre-clinical studies. Dr John Ford, CEO, Enterprise Therapeutics, said: “The dosing of the first person with CF in our Phase 2a trial of ETD001 represents an incredible milestone, testament to Enterprise’s dedication to advancing a novel approach to treating pwCF with the highest unmet medical need. ETD001 has already demonstrated an excellent safety profile in healthy participants, as well as a pharmacokinetic (PK) profile consistent with a long lung residency. We look forward to progressing ETD001 through Phase 2 trials and beyond.” Paul Russell, Head of Development, Enterprise Therapeutics, commented: “By targeting the underlying mechanisms of mucus congestion in the lungs through ENaC inhibition, ETD001 has the potential to be a transformative respiratory therapeutic. This is not only for the ~10% of pwCF who are not genetically suited to, or do not benefit from CFTR modulators, but also those suffering from other muco-obstructive lung diseases such as COPD and asthma. The commencement of our Phase 2a trial brings us an exciting step closer to realising that potential.” Dr Renu Gupta, CMO, Enterprise Therapeutics, said: “ We are grateful to the pwCF participating in our Phase 2 study of ETD001, and to the clinical investigators for achieving this major milestone. We are hopeful that our steadfast commitment to advancing this innovative ENaC targeting molecule, along with our partnerships with the CF community, will lead to a treatment that will vastly improve the lives of people living with CF.” SOURCE: Enterprise Therapeutics