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
therapeutics.
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.
When Being Cystic fibrosis Carrier Can Make You As Sick As Suffer.
Fostair or Seritide
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