Verona Pharma plc
("Verona Pharma" or the "Company")
Paper
demonstrating that RPL554 enhances CTFR activation in cystic
fibrosis airway epithelia published in American Journal of
Physiology
11 November 2015, Cardiff –
Verona Pharma plc (AIM: VRP.L), the drug development company
focused on first-in-class medicines to treat respiratory diseases,
announces that a paper examining the effect of Verona Pharma’s dual
PDE3/4 inhibitor, RPL554, on the Cystic Fibrosis Transmembrane
conductance Regulator (CFTR), an anion channel that is mutated in
cystic fibrosis (CF), has been published. The paper, entitled: “The
dual phosphodiesterase 3 and 4 inhibitor RPL554 stimulates CFTR and
ciliary beating in primary cultures of bronchial epithelia” was
published on-line in the peer reviewed Journal “American Journal of
Physiology - Lung Cellular and Molecular Physiology” on
6 November 2015.
In pre-clinical models of CF, RPL554 was shown to have
CFTR-stimulatory properties and that CFTR activation by RPL554 is
mediated by its inhibition of PDE4 in cells from CF patients with
the R117H/F508del mutation. RPL554-induced CFTR activity was
further increased by the CFTR potentiator Kalydeco (ivacaftor,
VX770) suggesting additional potential benefit by the drug
combination.* The work was partly funded through the Venture and
Innovation Award which Verona Pharma received from the UK CF Trust
in November 2014.
RPL554 is Verona Pharma’s lead pipeline asset. It is a
first-in-class drug initially being evaluated in Phase II clinical
trials as a nebulised treatment for acute exacerbations of COPD in
the hospital setting.
Dr Jan-Anders Karlsson, the CEO
of Verona Pharma, said:
“The results of this research further
support our view that RPL554 has potential in a number of discrete
indications. This peer-reviewed paper suggests that the drug could
be a novel therapeutic option for the treatment of patients with
cystic fibrosis. The data demonstrate that inhaled RPL554 activates
CFTR, and stimulates an increase in ciliary beat frequency, thus
having the potential to increase mucociliary clearance and as a
consequence the ability to help to reinstate a central function
impaired in this disease. We look forward to further exploring the
possible use of RPL554 in cystic fibrosis, as well as reporting
data from our Phase II trials of RPL554 in COPD and asthma in the
first half of 2016.”
The full abstract for this paper is reproduced below.
* This paper extends the research presented at the 2014 and 2015
North American Cystic Fibrosis Conference in the USA, announced in Company press releases on
29 September 2014 and 8 October 2015 respectively.
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
Title: The dual phosphodiesterase 3 and 4 inhibitor RPL554
stimulates CFTR and ciliary beating in primary cultures of
bronchial epithelia
Mark John Turner, Elizabeth Matthes, Arnaud Billet, Amy J.
Ferguson, David Y. Thomas,
Scott H Randell, Lawrence E.
Ostrowski, Kathy
Abbott-Banner, John W.
Hanrahan
American Journal of Physiology - Lung Cellular and Molecular
Physiology
Published 6 November 2015
DOI: 10.1152/ajplung.00324.2015
Cystic fibrosis (CF), a genetic disease caused by mutations in
the CFTR gene, is a life-limiting disease characterized by chronic
bacterial airway infection and severe inflammation. Some CFTR
mutants have reduced responsiveness to cAMP/PKA signalling, hence
pharmacological agents that elevate intracellular cAMP are
potentially useful for the treatment of CF. By inhibiting cAMP
breakdown, phosphodiesterase (PDE) inhibitors stimulate CFTR in
vitro and in vivo. Here, we demonstrate that PDE
inhibition by RPL554, a drug which has been shown to cause
bronchodilation in asthma and COPD patients, stimulates
CFTR-dependent ion secretion across bronchial epithelial cells
isolated from patients carrying the R117H/F508del CF genotype.
RPL554-induced CFTR activity was further increased by the
potentiator VX-770, suggesting additional benefit by the drug
combination. RPL554 also increased cilia beat frequency in primary
human bronchial epithelial cells. The results indicate RPL554 may
increase mucociliary clearance through stimulation of CFTR and
increasing ciliary beat frequency and thus could provide a novel
therapeutic option for CF.
-Ends-
For further information please
contact:
Verona Pharma plc |
Tel: +44 (0)20 3283 4200 |
Jan-Anders Karlsson, Chief Executive
Officer |
|
|
|
N+1 Singer |
Tel: +44 (0)20 7496 3000 |
Aubrey Powell / Jen Boorer |
|
|
|
FTI Consulting |
Tel: +44 (0)20 3727 1000 |
Simon Conway /
Stephanie Cuthbert /
Natalie Garland-Collins |
|
Notes to Editors
About Verona Pharma plc
Verona Pharma plc is a UK-based clinical stage biopharmaceutical
company focused on the development of innovative prescription
medicines to treat respiratory diseases with significant unmet
medical needs, such as chronic obstructive pulmonary disease
(COPD), asthma and cystic fibrosis.
Verona Pharma's lead drug, RPL554, is a first-in-class drug
currently in Phase II trials as a nebulised treatment for acute
exacerbations of COPD in the hospital setting. The drug is a
dual phosphodiesterase (PDE) 3/4 inhibitor and therefore has both
bronchodilator and anti-inflammatory effects, which are essential
to the improvement of patients with COPD and asthma.
Verona Pharma is also building a broader portfolio of
RPL554-containing products to maximise its benefit to patients and
its value. This includes the very significant markets for
COPD and asthma maintenance therapy. The Company is also
exploring the potential of the drug in different diseases, such as
cystic fibrosis, where it is in pre-clinical testing and has
received a Venture and Innovation Award from the Cystic Fibrosis
Trust.