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COPD - Cystic fibrosis news out..

New data supports RPL554 as a potential novel cystic fibrosis therapy

29 September 2014, Cardiff - Verona Pharma plc (AIM: VRP), the drug development

company focused on first-in-class medicines to treat respiratory diseases,

reports that RPL554, the Company's lead molecule, currently in phase 2 clinical

development for the treatment of acute COPD, may also be a novel treatment for

cystic fibrosis ("CF"), based on data that will be presented at The 28th Annual

North American Cystic Fibrosis Conference (NACFC), Atlanta, Georgia, USA,

October 9-11, 2014. This is the first time these data will be presented in a

peer-reviewed public forum.

The presentation, entitled "CFTR activation by the dual phosphodiesterase 3/4

inhibitor RPL554 and the MRP4 inhibitor MK571", reports data demonstrating the

ability of RPL554 to activate the cystic fibrosis transmembrane conductance

regulator ("CFTR"), an ion channel in cells lining the airways, which is

defective in CF patients1. Genetic mutations that reduce the function of CFTR

are responsible for the symptoms experienced by CF patients. CFTR activation

may also contribute to the efficacy of inhaled RPL554 already observed in COPD

and asthma. An abstract for the poster can be found on the conference website,

nacfconference.org/. A manuscript describing the full results from

these studies is being prepared for publication by the end of 2014 in an

appropriate peer-reviewed scientific journal.

Cystic fibrosis is an orphan disease with about 70,000 people afflicted

worldwide2. It is one of the most common life-threatening genetic conditions

affecting humans. There is currently no cure available and there is significant

demand for novel treatments. Verona Pharma will now further evaluate the

potential of RPL554 as a treatment for CF with academic collaborators in

relevant pre-clinical model systems.

Prof John Hanrahan, Director, CF Translational Research centre at McGill

University commented:

"In our experiments, RPL554 increased the activity of CFTR, ion channels on the

surface of cells obtained from the lining of the airway. In cystic fibrosis

patients it is the dysfunction of these ion channels, as a result of genetic

mutations, that is responsible for the symptoms of the disease. We will

continue to examine this effect of RPL554 in further studies. Ultimately, if

found effective and safe in cystic fibrosis patients, RPL554 could emerge as a

new medicine for this debilitating disease".

Dr Jan-Anders Karlsson, CEO of Verona Pharma, commented:

"Due to its mechanism of action, we expected that RPL554 might have utility in

other respiratory diseases in addition to COPD and asthma, such as

bronchiectasis and CF. These results support that hypothesis at least for CF.

We will now seek to build on these findings by testing the activity of RPL554

in patients with this orphan disease."

"We are currently focused on progressing RPL554 in phase 2 clinical trials for

COPD, initially positioning it as a novel treatment for acute exacerbations of

the disease. We are also building a broader franchise around this drug to

maximise its value, both to patients and to investors. We are therefore

exploring the potential of the drug in different diseases as well as in the

multi-blockbuster markets for COPD and asthma maintenance therapy. The results

outlined in this NACFC presentation suggest another tangible opportunity for us

to explore."

The NACFC is held under the auspices of the Cystic Fibrosis Foundation (CFF), a

non-profit organisation. The CFF is the world's leader in the search for a cure

for cystic fibrosis. They fund more CF research than any other organisation,

and nearly every CF drug available today was made possible because of CFF

support. The Foundation's focus is to support the development of new drugs to

fight the disease, improve the quality of life for those with CF, and

ultimately to find a cure.

1. Matthes, E., Billet, A., Darling, A., Goepp, J., Robert, R., Thomas, D.Y.,

Banner, K.H., Hanrahan, J.W.; CFTR activation by the dual phosphodiesterase

3/4 inhibitor RPL554 and the MRP4 inhibitor MK571, Abstract 277

2. cff.org

For further information please contact:

Verona Pharma plc Tel: +44 (0) 20 7863 3300

Jan-Anders Karlsson, CEO

N+1 Singer Tel: +44 (0)20 7496 3000

Aubrey Powell / Jen Boorer

FTI Consulting Tel: +44 (0)20 3727 1000

Julia Phillips / Simon Conway

Notes to Editors

About Verona Pharma plc

Verona Pharma is developing first-in-class drugs to treat respiratory disease,

such as COPD and asthma. The Company currently has two drug programmes, one of

which is in Phase 2 trials for two diseases. The lead programme, RPL554, is an

innovative dual phosphodiesterase (PDE) 3 and 4 inhibitor with both

bronchodilator and anti-inflammatory properties. In its second programme,

Verona Pharma is investigating novel anti-inflammatory molecules, called NAIPs,

for a wide range of respiratory and inflammatory diseases.

About RPL554 for the treatment of COPD and Asthma

Verona's lead drug, RPL554, is a dual phosphodiesterase (PDE) 3 and 4 inhibitor

being developed as a novel treatment for chronic obstructive airways disease

such as COPD (chronic obstructive pulmonary disorder) and asthma, with

bronchodilator and anti-inflammatory effects. Both effects are essential to

improve symptoms in patients with COPD or asthma. RPL554 is currently in Phase

2 for both diseases.

COPD is a chronic lung disease with significant unmet need for which current

treatment is far from optimal, as it often has unwanted side-effects and/or

limited effectiveness. COPD is most commonly characterised by fixed airflow

obstruction and chronic airways inflammation resulting from exposure to

irritants like tobacco smoke. Asthma, which remains one of the most common

chronic diseases in the world, is characterised by recurrent breathing problems

and symptoms such as breathlessness, wheezing, chest tightness, and coughing.

The combined market for COPD and asthma drugs is currently estimated to be

GBP20 billion (source: visiongain).

About the Cystic Fibrosis Translational Research centre (CFTRc)

The CFTRc was established in the Faculty of Medicine at McGill University in

2011 with $5.5M of infrastructure funding from the Canada Foundation for

Innovation. It comprises 28 researchers at McGill and other institutions from

Quebec to British Columbia. It provides core facilities and other resources for

CF research at the level of cells, tissues, and whole animals, integrating

physiological studies with chemical and structural biology and biochemical and

cell biological studies of the rescued mutant protein. It fosters interaction

with industry, advises members concerning technology transfer and commercial

agreements, and promotes preclinical and clinical studies of potential


About Cystic Fibrosis

Cystic fibrosis (CF) is an orphan disease that afflicts approximately 70,000

people worldwide. The disease affects mostly the lungs, and also the pancreas,

liver, and intestine. Difficulty breathing is the most serious symptom and

results from frequent lung infections. CF is caused by one of many different

mutations in the gene for the protein cystic fibrosis transmembrane conductance

regulator (CFTR). This protein is required to regulate the components of sweat,

digestive fluids, and mucus. Healthy people have two working copies of the CFTR

gene. Carriers have one working copy. People with CF have no working copy. CF

therefore has autosomal recessive inheritance. The underlying mechanism is

abnormal transport of chloride and sodium across the epithelium, which is the

cell layer that covers membranes over organs. This leads to thick, viscous

secretions. Individuals with cystic fibrosis can be diagnosed before birth by

genetic testing or by a sweat test in early childhood. The name cystic fibrosis

refers to the characteristic scarring (fibrosis) and cyst formation within the

pancreas, first recognised in the 1930s.

1 Reply

Thank you for this interesting article. cx


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