Enterprise Therapeutics granted ‘rare pediatric disease designation’ in the US for novel cystic fibrosis investigational therapy ETD001

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  • ETD001 is a novel, first in class blocker of the epithelial sodium channel (ENaC) aimed at treating people with cystic fibrosis without current effective therapies
  • ETD001 commenced Phase 2 clinical trials in July 2024, expected to complete in 2025

Brighton, UK, 26 September 2024: 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 23rd July 20242. 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 studies3.

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.”

  1. https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions
  2. https://enterprisetherapeutics.com/enterprise-therapeutics-doses-first-person-with-cystic-fibrosis-in-phase-2-trial-for-novel-therapy-etd001/
  3. https://enterprisetherapeutics.com/enterprise-therapeutics-publishes-preclinical-profile-of-etd001-a-novel-inhaled-enac-blocker/

Enterprise Therapeutics appoints Annabella Amatulli as Head of Regulatory Affairs

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  • Appointment brings extensive regulatory experience as lead asset ETD001 progresses through Phase 2 clinical trial for treatment of cystic fibrosis

Brighton, UK, 11 September 2024: 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 the appointment of Annabella Amatulli as Head of Regulatory Affairs.

In this newly created role, Annabella will be responsible for driving the Company’s regulatory strategy and working in close collaboration with clinical, medical, patient engagement, and market access teams. The primary focus of her role will be to support the ongoing Phase 2 clinical trial of lead asset ETD001, a novel long acting ENaC blocker which offers the potential to treat people with cystic fibrosis (CF) not currently benefitting from CFTR modulator therapies1. Annabella will also define the regulatory pathways for Enterprise’s pipeline of other novel low molecular weight compounds which also have first-in-class and best-in-class potential.

Annabella has more than 14 years’ experience working in pharmaceutical companies, with a focus on regulatory affairs. Prior to joining Enterprise, she was Head of Global Regulatory Sciences at Alfasigma, where she contributed to the growth of the company and the regulatory strategy for all products, across varying phases of development. Annabella has an extensive range of regulatory experience throughout Europe, the US and in other regions of the world. She has led interactions with health authorities including EMA, FDA, MHRA and NMPA to obtain Orphan Drug Designation, Fast Track and Breakthrough approvals for numerous candidates, negotiated Paediatric Investigation Plans, set up a global early access programme, and obtained global approval for a rare disease therapeutic.

Prior to Alfasigma, Annabella held various senior regulatory positions in both SMEs and large pharmas, including Chief Regulatory Officer at Napo Therapeutics and Global Regulatory Affairs Biotech & Development Director at Dompè Farmaceutici, as well as roles within Janssen-Cilag (J&J), Schering-Plough, and Mylan. As a member of the Pharma Trade Association, she led the regulatory workstream dedicated to advanced therapies (ATMPs). Annabella is also one of the founders of the Milan chapter of the Healthcare Businesswomen’s Association and is currently Regional Chair of the Southern Europe Region.

Dr John Ford, CEO, Enterprise Therapeutics, said: “We welcome Annabella as Head of Regulatory Affairs. Her broad experience in managing regulatory teams and liaising with health authorities will be hugely beneficial as we continue to progress our respiratory therapeutics programmes. Annabella’s expertise will prove especially valuable as we transition through Phase 2 clinical trials for our lead asset ETD001, moving closer to providing a novel treatment for all people with CF, including those with the highest unmet medical need.”

Annabella Amatulli, Head of Regulatory Affairs, Enterprise Therapeutics, added: “I am delighted to join Enterprise at such a pivotal time. The work that the Company is doing has the potential to vastly improve the lives of people with respiratory diseases. I look forward to working with the leadership team to help drive the continued development of the pipeline.”  

Enterprise Therapeutics Doses First Person with Cystic Fibrosis in Phase 2 Trial for Novel Therapy ETD001

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  • Trial aims to deliver clinical proof-of-concept and assess the safety profile of novel long acting ENaC inhibitor ETD001
  • ETD001, a CFTR mutation agnostic approach to CF, is focussed on providing a novel treatment for members of the CF community that do not benefit from currently available mutation-targeted therapies

Brighton, UK, 23 July 2024: 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 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.”

Enterprise Therapeutics appoints Dr Renu Gupta as Chief Medical Officer and Dr Janet Hammond as Non-Executive Director

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Appointments bring additional respiratory and late clinical-stage drug development experience as Company commences Phase 2a clinical trial of its lead asset

Brighton, UK, 17 June 2024:Enterprise Therapeutics Ltd (Enterprise), a biopharmaceutical company dedicated to the discovery and development of novel therapies to improve the lives of patients suffering from respiratory disease, today announced the appointment of Dr Renu Gupta as CMO (Chief Medical Officer) and Dr Janet Hammond as a Non-Executive Director.

Dr Gupta is a physician-scientist and industry leader, with more than 20 years of experience as a CMO, most recently at Promedior, Inc., a member of the Roche Group. During a career spanning over 30 years in the biopharmaceutical industry, she has held various roles within research and development, executive management, and as a Board member, including at Global Bio-Pharma, Corbus Pharmaceuticals, Breath Therapeutics, Insmed, Inc. (NASDAQ: INSM), Novartis, and Bristol-Myers Squibb (BMS). Dr Gupta has been instrumental in implementing innovative clinical and regulatory strategies and development pathways to advance targets, including for rare disease indications, forming productive private-public sector partnerships, raising capital, and ultimately advancing molecules from drug discovery through approvals in the major global markets. She received her bachelor and medical degrees from the University of Zambia and completed her medical and post-doctoral training at Albert Einstein Medical Center, the Wistar Institute of Anatomy and Biology, the Children’s Hospital of Philadelphia, and the University of Pennsylvania.

Dr Hammond has over 20 years’ experience in the pharmaceutical industry, during which time she has overseen the development and successful approval of several drugs. She is currently Chief Development Officer at Atea Pharmaceuticals, a Boston-based biotech focused on the development of antiviral drugs for life-threatening infectious diseases. Prior to joining Atea, Janet was Vice President and Head of Infectious Diseases and General Medicine at AbbVie, Inc., and Senior Vice President and Global Head of Infectious Diseases at Hoffmann-la Roche. She obtained her MD and PhD from the University of Cape Town where she specialised in Pulmonary/Critical Care Medicine, holds a Masters in Clinical Investigation from Johns Hopkins University, and carried out training in Infectious Diseases at Duke and Johns Hopkins Universities.

 Dr John Ford, CEO, Enterprise Therapeutics, said: “We are delighted to welcome Renu as CMO and Janet to the Board. Renu’s successful track record in developing innovative respiratory medicines will be a great asset to the team, while Janet’s extensive experience in driving late-stage clinical development programmes will be an invaluable addition to the Board. Both appointments substantially strengthen our team as we work towards delivering clinical proof of concept for our lead asset ETD001, taking us a step closer to providing an effective therapy for people with cystic fibrosis not benefitting from CFTR modulators.”

Dr Renu Gupta, CMO, Enterprise Therapeutics, added: “Enterprise Therapeutics’ development programme shows impressive dedication and great promise for the treatment of those people with cystic fibrosis not currently served by existing therapies. I am excited to join the Company, and look forward to working with John, Janet, and the rest of the team as we progress through Phase 2 trials.”

Dr Janet Hammond, Non-Executive Director, Enterprise Therapeutics, commented: “The work that Enterprise Therapeutics is doing has the potential to significantly improve the lives of patients living with respiratory diseases. I look forward to supporting the Company in this goal by working alongside the management team to help drive the success of its clinical programmes.”

For more information about Enterprise Therapeutics, visit www.enterprisetherapeutics.com

Enterprise Therapeutics publishes preclinical profile of ETD001, a novel inhaled ENaC blocker

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  • Low doses of ETD001 demonstrate exceptionally long duration of action in sheep model of airway mucus clearance
  • Report in Journal of Cystic Fibrosis discloses best-in-class profile of ETD001
  • ETD001 scheduled to commence Phase 2 clinical study in people with cystic fibrosis in summer 2024

Brighton, UK, 12 June 2024: 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 Journal of Cystic Fibrosis1. The paper describes low doses of the ENaC blocker ETD001, Enterprise’s lead asset, enhancing airway mucus clearance with an exceptionally long duration of action in a sheep model.

This study indicates that ETD001, at a dose level that was well tolerated in healthy volunteer studies, provides an opportunity to test whether a long-acting ENaC blocker can deliver benefit to people with cystic fibrosis (pwCF). ETD001 is scheduled to commence a Phase 2 clinical study in pwCF in summer 2024, to understand whether 28 days of treatment will improve lung function.

Blocking ENaC in the airways offers a novel approach to improve mucus clearance in pwCF, including in the ≥10% of individuals who are either intolerant of or genetically unsuited to CFTR modulators. Recently, several other ENaC blocking drugs (VX-371, AZD5634, BI 1265162, QBW276) failed to show any benefit in clinical trials. This study provides a potential explanation for these failures as data from the sheep model indicate that each may have been dosed in clinical trials at a dose too low to observe an extended duration of action on mucus clearance.

Dr Henry Danahay, Head of Biology, Enterprise Therapeutics, and lead author of the paper, said: “This data provides strong evidence that ETD001 has a superior profile compared to other inhaled ENaC blockers. Along with the results from the Phase 1 trials where ETD001 was well-tolerated, this study supports our high level of confidence going into the Phase 2 clinical trial. We remain passionate in our drive to discovery novel therapies that have the potential to transform the lives of all people with cystic fibrosis.”

  1. https://www.sciencedirect.com/science/article/pii/S156919932400081X

For more information about Enterprise Therapeutics, visit www.enterprisetherapeutics.com

Enterprise Therapeutics Closes £26 million ($33.1 million) Series B Follow-on Financing

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  • Round led by new investor Panakes, with participation from all existing investors
  • Funding will support Phase 2a clinical proof of concept trial in cystic fibrosis for a novel first in class ENaC blocker (ETD001) and pipeline expansion
  • Dr Rob Woodman, Partner at Panakes, appointed to the Board of Directors

Brighton, UK, 30 January 2024: Enterprise Therapeutics Ltd (Enterprise), a biopharmaceutical company dedicated to the discovery and development of novel therapies to improve the lives of patients suffering from respiratory disease, today announced that it has closed a £26 million ($33.1 million USD) Series B follow-on financing round, led by Panakes Partners. Existing investors Versant Ventures, Novartis Venture Fund, Forbion, Epidarex Capital and IP Group also participated. Alongside the financing, Dr Rob Woodman, Partner at Panakes, joins Enterprise’s Board of Directors.

The investment will fund the Phase 2a clinical trial of the Company’s lead programme, ETD001, to deliver clinical proof of concept to treat cystic fibrosis. ETD001, a novel low molecular weight compound with first-in-class potential, targets the ENaC ion channel in the airway epithelium, increasing the hydration and clearance of mucus. ETD001 has been designed to be long acting, delivering durable target engagement, which is expected to drive substantial improvements in lung function. The trial will involve a cross-over design study assessing FEV1 lung function in people with cystic fibrosis who are either ineligible for or are not receiving CFTR modulators.

Enterprise’s pipeline of disease-modifying therapies targets the underlying mechanisms of mucus congestion, to enhance the clearance of mucus from the airways, restore lung function, and ultimately to reduce morbidity and mortality in chronic respiratory diseases of high unmet medical need, such as cystic fibrosis, chronic obstructive pulmonary disease and severe asthma. Enterprise has established an Italian subsidiary to support R&D activities. This funding will enable the expansion of the Company’s clinical activities into Italy via addition of clinical investigator sites and progression of its other preclinical programmes targeting mucus congestion.

 Dr John Ford, CEO, Enterprise Therapeutics, said: “We have made tremendous progress to date in developing novel therapeutics for patients suffering from chronic respiratory diseases. Such medicines are essential to reduce the frequency of lung infections and improve patient quality of life. On behalf of Enterprise’s leadership team, I would like to thank all our investors, both historical and new, for their recognition of the strength of Enterprise’s pipeline, and welcome Rob as a valuable addition to the Board.”

Dr Rob Woodman, Partner, Panakes, commented: “Knowing the quality and track record of the Enterprise team, I am delighted to now be part of the next stage of its development. We strongly believe that Enterprise’s approach offers the potential to impact the future of therapeutics for a range of respiratory diseases, including cystic fibrosis, and that the Company is well positioned to be a leader in the field.”

For more information about Enterprise Therapeutics, visit www.enterprisetherapeutics.com