Verona Pharma PLC RPL554 paper published in American Journal of Physiology

 
TIDMVRP 
 
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. 
 
 
 
END
(END) Dow Jones Newswires
November 11, 2015 02:00 ET (07:00 GMT)
Verona Pharma (LSE:VRP)
Historical Stock Chart
From Jun 2024 to Jul 2024