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Enterprise Therapeutics’ First-in-Class TMEM16A potentiator program for treatment of cystic fibrosis and other respiratory diseases acquired by Roche

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  • Enterprise’s novel TMEM16A potentiator portfolio includes ETD002, a first in class compound which is currently in Phase 1
  • TMEM16A potentiation is a novel therapeutic approach applicable to all cystic fibrosis patients, independent of CFTR genotype, and may provide benefit in other respiratory diseases
  • Enterprise’s shareholders received an upfront payment of £75 million

Brighton, UK, 07 October 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 its novel TMEM16A potentiator portfolio has been fully acquired by Roche and will be developed by Genentech, a member of the Roche Group. The portfolio includes ETD002 which recently entered Phase 1 trials.

Enterprise’s shareholders received an upfront payment of £75 million and are eligible to receive additional contingent payments, to be made based on the achievement of certain predetermined milestones.

The TMEM16A portfolio is focused toward treating all people with cystic fibrosis (CF), with potential to benefit people with other severe respiratory diseases characterised by excessive mucus congestion.

 Dr John Ford, CEO, Enterprise Therapeutics, said: “Roche and Genentech have a proven track record of bringing new medicines to people with respiratory diseases, and have recognised the opportunity that our TMEM16A potentiator portfolio presents. I am very proud of the team at Enterprise for identifying and developing this innovative approach to treat patients, with ETD002 the first of our compounds to reach clinical stage. TMEM16A potentiation has the potential to significantly increase the quality of life for people living with cystic fibrosis, for many of whom existing therapies are not effective.”

 Dr James Sabry, MD, PhD, Global Head of Pharma Partnering, Roche, commented: “We are excited to add Enterprise’s TMEM16A potentiator program to our existing respiratory portfolio. We have deep capabilities in this area and look forward to a robust program focused on helping cystic fibrosis patients and patients suffering from other muco-obstructive disorders as quickly as possible.”

CF is estimated to affect 75,000 people globally. One of the main causes of difficulty in breathing and increased risk of infection is mucus congestion in the lungs. The ETD002 compound 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) gene, that normally produces 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 potentially applicable to all people with CF, and perhaps patients with non-CF muco-obstructive lung disease.

Moelis acted as financial advisor and Goodwin Procter acted as legal counsel to Enterprise Therapeutics.

Enterprise Therapeutics doses first subjects in Phase 1 trial for First-in-Class cystic fibrosis therapy ETD002

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  • 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.

Enterprise Therapeutics appoints Dr David Morris MD as Chief Medical Officer

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Dr Morris will lead Enterprise’s therapeutics development strategy and drive the Company’s two lead respiratory programmes through the clinic

Brighton, UK, 10 February 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 appointed Dr David Morris MD as Chief Medical Officer to lead the Company’s respiratory programmes. These programmes include clinical development for ETD002, a first-in-class TMEM16A potentiator and ETD001, a novel ENaC blocker, therapies aimed at treating all cystic fibrosis patients.

Enterprise Therapeutics is developing novel disease-modifying therapies which target 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 including cystic fibrosis (CF).

Dr Morris joins Enterprise from the Novartis Venture Fund, an investor in Enterprise, where he is currently a Managing Director, and where he will maintain an appointment as an Operating Partner. Prior to his career in venture capital David held various leadership roles in the Novartis Pharmaceuticals development organisation, including Development Franchise Head of Respiratory, Development Franchise Head of Primary Care, and Global Head of Clinical Operations, Analytics and Regions, where he was responsible for all aspects of global clinical trials operations, monitoring, and reporting. In addition, David has also held Director level roles in respiratory discovery research and translational medicine at Roche.

Dr Morris received his Bachelors and Medical Degrees with distinction from the University of Rochester.  His clinical training in internal medicine and pulmonary and critical care medicine were at Massachusetts General Hospital and the University of California, San Francisco.  Before joining industry, he held faculty appointments and led basic and translational research programs at University of California, San Francisco and Yale University School of Medicine.

Dr John Ford, CEO, Enterprise Therapeutics, said: “The knowledge and experience David has gained through his successful career in biopharmaceutical discovery and development, as well as his stellar sector expertise in respiratory biology, will be an invaluable asset as we work to define our strategy to progress our respiratory programmes which will initially focus on CF.”

Dr David Morris, CMO, Enterprise Therapeutics, said: “Enterprise’s programmes show great potential to deliver disease-modifying, clinically effective candidates for a significant number of patients with respiratory diseases, including all CF patients regardless of underlying mutations. I am excited to become more closely involved with the team moving forward, at this exciting point in the Company’s development.”

Enterprise Therapeutics publishes paper on novel therapeutic approach for treatment of all cystic fibrosis patients

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  • “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