• ETD002 is a novel TMEM16A chloride channel potentiator
• Therapy applicable to all cystic fibrosis patients, independent of genotype

Brighton, UK, 17 August 2020: Enterprise Therapeutics Ltd (Enterprise), a biopharmaceutical company dedicated to the discovery and development of novel therapies to improve the lives of patients suffering with respiratory disease, today announced it has successfully dosed the first subjects in a Phase 1 trial for its novel inhaled cystic fibrosis therapy, ETD002. The first-in-man safety study is being conducted in healthy participants with ETD002, a TMEM16A potentiator aimed at treating all people with cystic fibrosis (CF).

CF is estimated to affect 75,000 people globally. One of the main causes of difficulty in breathing and increased risk of infection in CF is mucus congestion in the lungs. Enterprise’s proprietary compound ETD002 targets the underlying mechanisms of mucus congestion, and is expected to restore lung function, reduce the frequency of lung infections and improve patient quality of life. CF is caused by loss of function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel highly expressed by the airway epithelium. Increasing anion conductance via CFTR modulation is a clinically validated approach for treating CF, however it is not currently available or effective for all people with CF.

In pre-clinical models, Enterprise has demonstrated that ETD002 enhances the activity of TMEM16A, an alternative anion channel present in airway epithelial cells, and by doing so increases anion and fluid flow into the airways, thinning the mucus and increasing its clearance. As TMEM16A potentiation is independent of the mutational status of CFTR, this makes the approach applicable to all people with CF, and potentially patients with non-CF lung disease. Additionally, ETD002 is expected to deliver benefit as a monotherapy and in combination with other therapies, including CFTR repair.

Dr John Ford, CEO, Enterprise Therapeutics, said: “Considerable efforts to identify and develop this innovative compound have resulted in a TMEM16A potentiator that has the potential to significantly increase the quality of life for people living with CF, for many of whom existing therapies are not effective. We are excited to have begun the clinical stage of development for ETD002.”

 Dr David Morris, CMO, Enterprise Therapeutics, said: “Although CFTR modulators have successfully demonstrated improved clinical outcomes in those genetically suited to these therapies, we are hopeful that TMEM16A potentiation via ETD002 will provide clinical benefit to the many people with CF who do not share these CFTR mutations. We look forward to generating our first data in human volunteers over the next few months and are grateful to the subjects and investigators who are helping us to advance this novel treatment for individuals with CF.”

This work is in part funded by a Therapeutics Development Award from the Cystic Fibrosis Foundation to Enterprise Therapeutics.

• “TMEM16A Potentiation: A Novel Therapeutic Approach for the Treatment of Cystic Fibrosis” published in American Journal of Respiratory and Critical Care Medicine
• Paper demonstrates first in class TMEM16A chloride channel potentiators, to accelerate mucociliary clearance
• Co-authored by researchers from University of Sussex, University of North Carolina and University of Miami

Brighton, UK, 08 January 2020: Enterprise Therapeutics Ltd (Enterprise), a biopharmaceutical company dedicated to the discovery and development of novel therapies to improve the lives of patients suffering with respiratory disease, today announced the publication of its first peer-reviewed paper. The open access paper, published in the American Journal of Respiratory and Critical Care Medicine¹, describes TMEM16A potentiation via ETX001 as a novel approach for the treatment of cystic fibrosis (CF). The research was conducted in collaboration with University of Sussex, University of North Carolina and University of Miami.

The paper, entitled “TMEM16A Potentiation: A Novel Therapeutic Approach for the Treatment of Cystic Fibrosis”, demonstrates the ability of Enterprise’s proprietary compound, ETX001, to enhance the activity of TMEM16A in human bronchial epithelial cells from CF patients, increasing epithelial fluid secretion and mucus clearance providing the first pre-clinical proof of principle for this approach.

CF is estimated to affect 75,000 patients globally and is caused by loss of function mutations in the anion channel, cystic fibrosis transmembrane conductance regulator (CFTR). Increasing anion conductance via CFTR modulation is a clinically validated approach for treating CF, however it does not treat ≥10% of patients with a combination of nonsense and other rare mutations. In addition, many patients eligible for CFTR repair therapy do not benefit from these therapies. TMEM16A potentiation offers a non-CFTR mediated approach for the treatment of CF and can be delivered as a monotherapy or in combination with other therapies such as CFTR repair.

Dr Henry Danahay, Head of Biology, Enterprise Therapeutics, and lead author of the paper, said:

“We have successfully demonstrated the positive effects of ETX001 on both airway fluid secretion and mucus clearance in cells from CF patients. Given the percentage of the population of CF patients who are not genetically matched to existing CFTR repair therapies, this paper builds a strong case for testing TMEM16A potentiation in the clinic.”

Authors on the paper include Henry L Danahay (Enterprise Therapeutics), Sarah Lilley (Sussex Drug Discovery Centre, University of Sussex), Roy Fox (Sussex Drug Discovery Centre, University of Sussex), Holly Charlton (Sussex Drug Discovery Centre, University of Sussex), Juan Sabater (Mount Sinai Medical Centre, University of Miami), Brian Button (Department of Biochemistry & Biophysics, UNC Chapel Hill, North Carolina), Clive McCarthy (Enterprise Therapeutics), Stephen P Collingwood (Enterprise Therapeutics), and Martin Gosling (Enterprise Therapeutics, and Sussex Drug Discovery Centre, University of Sussex).

This work was in part funded by a Therapeutics Development Award from the Cystic Fibrosis Foundation to Enterprise Therapeutics.

¹https://www.atsjournals.org/doi/abs/10.1164/rccm.201908-1641OC

Appointment brings significant commercial pharma experience as Enterprise Therapeutics’ two lead respiratory programmes are progressed towards the clinic

Brighton, UK, 25 March 2019: Enterprise Therapeutics Ltd (Enterprise), a biopharmaceutical company dedicated to the discovery and development of novel therapies to improve the lives of patients suffering with respiratory disease, today announced the appointment of Amit D. Munshi as Non-Executive Chairman of the Board of Directors. Amit’s appointment is significant for Enterprise, strengthening the ability of the leadership team as it transitions to a clinical stage development company, addressing areas of critical unmet needs in respiratory disease.

Mr. Munshi has more than 28 years of global biopharmaceutical industry experience in executive management, business development, product development and portfolio management, and has served on several private and public company boards. He is Director, President and Chief Executive Officer of Arena Pharmaceuticals, Inc., a Nasdaq-listed biopharmaceutical company which has a proprietary pipeline in mid-late stage clinical development. Previously, Mr. Munshi served as President and Chief Executive Officer of Epirus Biopharmaceuticals, Inc. and Percivia LLC. Prior to Epirus and Percivia, he was a co-founder and Chief Business Officer of Kythera Biopharmaceuticals, Inc., and held multiple leadership positions at Amgen, Inc. Mr. Munshi holds a B.S. in Economics and a B.A. in History from the University of California, Riverside, and an M.B.A. from the Peter F. Drucker School of Management at Claremont Graduate University.

Dr John Ford, CEO, Enterprise Therapeutics, said: “We are delighted that Amit has chosen to join as Chairman at this exciting time for the Company, as we prepare to take our two lead programmes into the clinic in the next 12 months. Amit brings a wealth of experience in product development, portfolio management and commercial strategy in both the US and EU that will be critical in driving the Company through the next phase of its development.”

Amit D. Munshi, Chairman, Enterprise Therapeutics, said: “Enterprise is led by an impressive management team with significant expertise and experience, and is backed by a high-profile syndicate of investors. I believe the Company and its therapeutic programmes have real potential to make a difference to the lives of respiratory disease patients.”

Enterprise Therapeutics is developing novel disease-modifying therapies which target underlying mechanisms of mucus congestion, enhancing the clearance of mucus from the airways, thereby restoring lung function and reducing morbidity and mortality in respiratory diseases. Enterprise’s programmes differentiate from the current standard of care as they aim to deliver disease-modifying, clinically effective candidates for a significant number of patients with respiratory diseases, including all CF patients, regardless of underlying mutations, and a large percentage of patients with COPD and severe asthma.

In April 2018 Enterprise closed an oversubscribed £29 million ($41 million USD) Series B round co-led by Versant Ventures and Novartis Venture Fund. The syndicate also included new investor Forbion, founding investor Epidarex Capital and existing investor IP Group.

Brighton, UK – 12 April 2018: Enterprise Therapeutics Ltd (Enterprise), a biopharmaceutical company dedicated to the research and development of novel therapies for the treatment of respiratory diseases, today announced that it has closed an oversubscribed £29 million ($41 million USD) Series B round co-led by Versant Ventures and Novartis Venture Fund. The
syndicate also included new investor Forbion, founding investor Epidarex Capital and existing investor IP Group.

The investment will fund the Company’s drug discovery pipeline of muco-regulatory therapies into clinical development, enabling new treatment options for cystic fibrosis, chronic obstructive pulmonary disease and severe asthma.

Enterprise Therapeutics is developing muco-regulatory therapies to treat patients with respiratory diseases of high unmet medical need, where mucus obstruction reduces lung function, leading to difficulty in breathing and recurrent lung infections. These novel therapies target the ion channels TMEM16A and ENaC, to increase the hydration and clearance of mucus. Enterprise Therapeutics has also identified novel targets and compounds that reduce mucus production, an approach that complements mucus hydration therapies.

Commenting on the fundraising, Dr John Ford, CEO, Enterprise Therapeutics, said: “Attracting this syndicate of leading life science investors is a reflection of what the Company has achieved to date and the strength of our pipeline. At Enterprise, we believe new therapies that target the underlying mechanisms of mucus congestion are essential to reduce the frequency of
lung infections and improve patient quality of life.”

Dr Alex Mayweg, Partner, Versant Ventures, commented: “We are very encouraged by progress the Enterprise team made in generating candidates for highly sought-after but challenging targets. This financing should enable introduction of novel therapeutics for patients with cystic fibrosis and other respiratory diseases.”

Dr David Morris, Venture Partner, Novartis Venture Fund, commented: “Our focus is on finding solutions for unmet needs and clinical impact, an area where Enterprise Therapeutics is making excellent progress for respiratory disease patients. We believe this additional round of funding puts the Company in a strong position as it continues to progress towards the clinic.”

“Forbion focuses on supporting novel approaches that have the potential to truly impact the future of medicine” commented Dr Geert-Jan Mulder, Managing Partner, Forbion. “As Enterprise Therapeutics has both a highly innovative R&D pipeline and an experienced leadership team, the Company in our view is well positioned to become a key player in the field of novel respiratory medicine.”

Brighton, UK – 10th November, 2016: Enterprise Therapeutics Ltd, a drug discovery company dedicated to the research and development of novel therapies for the treatment of respiratory diseases, today announced that it has closed a £4 million ($5 million USD) financing. The funding was led by existing investors Epidarex Capital and Imperial Innovations and will be used to accelerate the Company’s three drug discovery projects towards drug candidate selection.

Enterprise Therapeutics is developing novel muco-regulatory therapies for patients suffering with cystic fibrosis (CF), Chronic Obstructive Pulmonary Disease (COPD) and severe asthma. To achieve this, the Company is targeting mechanisms that increase the clearance of mucus or reduce levels of mucus production in order to alleviate the symptoms and complications
associated with respiratory disease.

Commenting on the fundraising, Dr John Ford, CEO, Enterprise Therapeutics, said: “Respiratory disease remains an area of high unmet medical need especially in the area of CF where existing therapies do not treat all patients. This additional funding will allow us to advance our research projects and move closer towards our goal of evaluating the efficacy of muco-regulatory drugs in patients. I look forward to working with the team and our investors in this important next
stage of growth.”

Dr Liz Roper, Investor Director, Epidarex, commented: “Based on excellent achievement of project milestones across all three discovery projects at Enterprise Therapeutics we are providing this additional investment to put the company in a strong position as it continues to progress towards the clinic. We are committed to the novel muco-regulatory approach that
Enterprise is taking to combat respiratory diseases.”

Dr Rob Woodman, Investor Director, Imperial Innovations commented: “Enterprise Therapeutics has made significant progress in the 18 months since Imperial Innovations first invested. We believe that the Company has the potential to become a leading player in respiratory disease.”