New data supports RPL554 as a potential CF therapy

Verona Pharma plc ("Verona Pharma" or the "Company") New data supports RPL554 as a potential novel cystic fibrosis therapy 29 September 2014, Cardiff - Verona Pharma plc (AIM: VRP), the drug developmentcompany focused on first-in-class medicines to treat respiratory diseases,reports that RPL554, the Company's lead molecule, currently in phase 2 clinicaldevelopment for the treatment of acute COPD, may also be a novel treatment forcystic fibrosis ("CF"), based on data that will be presented at The 28th AnnualNorth American Cystic Fibrosis Conference (NACFC), Atlanta, Georgia, USA,October 9-11, 2014. This is the first time these data will be presented in apeer-reviewed public forum. The presentation, entitled "CFTR activation by the dual phosphodiesterase 3/4inhibitor RPL554 and the MRP4 inhibitor MK571", reports data demonstrating theability of RPL554 to activate the cystic fibrosis transmembrane conductanceregulator ("CFTR"), an ion channel in cells lining the airways, which isdefective in CF patients1. Genetic mutations that reduce the function of CFTRare responsible for the symptoms experienced by CF patients. CFTR activationmay also contribute to the efficacy of inhaled RPL554 already observed in COPDand asthma. An abstract for the poster can be found on the conference website,https://www.nacfconference.org/. A manuscript describing the full results fromthese studies is being prepared for publication by the end of 2014 in anappropriate peer-reviewed scientific journal. Cystic fibrosis is an orphan disease with about 70,000 people afflictedworldwide2. It is one of the most common life-threatening genetic conditionsaffecting humans. There is currently no cure available and there is significantdemand for novel treatments. Verona Pharma will now further evaluate thepotential of RPL554 as a treatment for CF with academic collaborators inrelevant pre-clinical model systems. Prof John Hanrahan, Director, CF Translational Research centre at McGillUniversity commented: "In our experiments, RPL554 increased the activity of CFTR, ion channels on thesurface of cells obtained from the lining of the airway. In cystic fibrosispatients it is the dysfunction of these ion channels, as a result of geneticmutations, that is responsible for the symptoms of the disease. We willcontinue to examine this effect of RPL554 in further studies. Ultimately, iffound effective and safe in cystic fibrosis patients, RPL554 could emerge as anew 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 inother respiratory diseases in addition to COPD and asthma, such asbronchiectasis 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 RPL554in patients with this orphan disease." "We are currently focused on progressing RPL554 in phase 2 clinical trials forCOPD, initially positioning it as a novel treatment for acute exacerbations ofthe disease. We are also building a broader franchise around this drug tomaximise its value, both to patients and to investors. We are thereforeexploring the potential of the drug in different diseases as well as in themulti-blockbuster markets for COPD and asthma maintenance therapy. The resultsoutlined in this NACFC presentation suggest another tangible opportunity for usto explore." The NACFC is held under the auspices of the Cystic Fibrosis Foundation (CFF), anon-profit organisation. The CFF is the world's leader in the search for a curefor cystic fibrosis. They fund more CF research than any other organisation,and nearly every CF drug available today was made possible because of CFFsupport. The Foundation's focus is to support the development of new drugs tofight the disease, improve the quality of life for those with CF, andultimately 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. www.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 ofwhich is in Phase 2 trials for two diseases. The lead programme, RPL554, is aninnovative dual phosphodiesterase (PDE) 3 and 4 inhibitor with bothbronchodilator 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 inhibitorbeing developed as a novel treatment for chronic obstructive airways diseasesuch as COPD (chronic obstructive pulmonary disorder) and asthma, withbronchodilator and anti-inflammatory effects. Both effects are essential toimprove symptoms in patients with COPD or asthma. RPL554 is currently in Phase2 for both diseases. COPD is a chronic lung disease with significant unmet need for which currenttreatment is far from optimal, as it often has unwanted side-effects and/orlimited effectiveness. COPD is most commonly characterised by fixed airflowobstruction and chronic airways inflammation resulting from exposure toirritants like tobacco smoke. Asthma, which remains one of the most commonchronic diseases in the world, is characterised by recurrent breathing problemsand symptoms such as breathlessness, wheezing, chest tightness, and coughing.The combined market for COPD and asthma drugs is currently estimated to beGBP20 billion (source: visiongain). About the Cystic Fibrosis Translational Research centre (CFTRc) The CFTRc was established in the Faculty of Medicine at McGill University in2011 with $5.5M of infrastructure funding from the Canada Foundation forInnovation. It comprises 28 researchers at McGill and other institutions fromQuebec to British Columbia. It provides core facilities and other resources forCF research at the level of cells, tissues, and whole animals, integratingphysiological studies with chemical and structural biology and biochemical andcell biological studies of the rescued mutant protein. It fosters interactionwith industry, advises members concerning technology transfer and commercialagreements, and promotes preclinical and clinical studies of potentialtherapeutics. About Cystic Fibrosis Cystic fibrosis (CF) is an orphan disease that afflicts approximately 70,000people worldwide. The disease affects mostly the lungs, and also the pancreas,liver, and intestine. Difficulty breathing is the most serious symptom andresults from frequent lung infections. CF is caused by one of many differentmutations in the gene for the protein cystic fibrosis transmembrane conductanceregulator (CFTR). This protein is required to regulate the components of sweat,digestive fluids, and mucus. Healthy people have two working copies of the CFTRgene. Carriers have one working copy. People with CF have no working copy. CFtherefore has autosomal recessive inheritance. The underlying mechanism isabnormal transport of chloride and sodium across the epithelium, which is thecell layer that covers membranes over organs. This leads to thick, viscoussecretions. Individuals with cystic fibrosis can be diagnosed before birth bygenetic testing or by a sweat test in early childhood. The name cystic fibrosisrefers to the characteristic scarring (fibrosis) and cyst formation within thepancreas, first recognised in the 1930s.