Poster Presentation at ATS

21 May 2014 Verona Pharma plc ("Verona Pharma" or the "Company") Data highlighting synergistic action of novel dual PDE3/4 inhibitor RPL554 with muscarinic receptor antagonists and beta-adrenoceptor agonists in reversing bronchoconstriction presented at ATS international conference Verona Pharma plc (AIM: VRP), the drug development company focused on"first-in-class" medicines to treat respiratory diseases, today announces thata poster was presented on Tuesday 20 May as part of the scientific programme atAmerican Thoracic Society (ATS) International Conference, San Diego, USA, 16-21May 2014. The abstract for this poster is reproduced below. [Poster Board # A52] RPL554, A Dual Phosphodiesterase (PDE) 3/4 Inhibitor ActsSynergistically With Muscarinic Receptor Antagonists And Beta-AdrenoceptorAgonists To Produce Bronchodilation In Vivo, [Publication Number: A4218] S. Keir, PhD, C. Page, PhD Introduction: RPL554 is a novel PDE3/4 inhibitor in development for thetreatment of respiratory diseases, including asthma and COPD. We have recentlyreported that RPL554 induces a synergistic interaction with muscarinicantagonists in isolated human bronchi (Calzetta et al, 2013). This studyinvestigates the ability of RPL554 to reverse the bronchoconstriction inducedby bombesin and potential synergistic effects when RPL554 is administered incombination with atropine or salbutamol. Methods: Guinea pigs were anaesthetised and ventilated. Bronchoconstriction wasinduced by the intravenous administration of bombesin (2µg/ml; 5 ml/hr).Bronchodilation was induced by the iv. administration of RPL554 alone atvarious doses, or in combination with sub maximal doses of atropine (2µg/kg) orsalbutamol (20µg/kg), doses selected following studies generating adose-response curve for both atropine and salbutamol to select a dose resultingin approximately 20% reduction in airways obstruction. Total lung resistance(RL) and mean arterial blood pressure were measured. Data are expressed as %reduction in bronchoconstriction or blood pressure. Results: RPL554 caused a dose-dependent relaxation of guinea pig airways from10-80µg/kg. In combination with 2µg/kg atropine (a dose that caused 22.3 + 4.9% reduction in RL), a submaximal dose of RPL554 (20µg/kg) caused a greaterrelaxation of the airways than this dose of RPL554 administered alone.Furthermore, in combination with 20µg/kg salbutamol (a dose that caused 34.2 +11.1 % reduction in RL), RPL554 also resulted in greater relaxation of theairways (Table 1). The iv. administration of 20µg/kg RPL554 caused a reductionin mean arterial blood pressure, a response which was not potentiated whenco-administered with either (control: 37.3 + 6.7%, + 2µg/kg atropine: 35.3 +4.3 %; + 20µg/kg salbutamol: 23.3 + 13.0%). Table 1: % Reduction in RL RPL554 control RPL554 + atropine (2µg/kg) RPL554 + salbutamol (20µg/kg) 10µg/kg 7.4 +1.9 41.7 + 1.2 63.7 + 22.4 20µg/kg 24.6 + 4.3 76.5 + 8.8 66.0 + 12.9 40µg/kg 55.2 + 6.2 84.3 +9.1 76.3 + 17.4 80µg/kg 65.1 + 5.3 81.9 + 4.7 77.6 + 6.3 Conclusions: Our results provide further evidence that RPL554 is an effectivebronchodilator, when combined with either the muscarinic receptor antagonistatropine or the β2-adrenoceptor agonist salbutamol has synergistic activitiesas a bronchodilator, but does not interact with the drug classes on bloodpressure. Given the recent report that RPL554 is an effective bronchodilator in subjectswith asthma or COPD (Francioisi et al, 2013), our results suggest that thisdrug could provide additional clinical benefit when administered with otherbronchodilators. Calzetta et al. 2013 J. Pharm. Exp. Ther. 346:414-423 Francioisi et al. 2013 AJRCCM 187:A3875 -Ends- For further information please contact: Verona Pharma plc Tel: 020 7863 3300Clive Page, ChairmanJan-Anders Karlsson, CEO WH Ireland Limited Tel: 020 7220 1666Chris FieldingNick Field FTI Consulting Tel: 020 3727 1000Julia PhillipsSimon ConwayVictoria Foster Mitchell Notes to Editors About Verona Pharma plc Verona Pharma is developing first-in-class drugs to treat respiratory disease,such as COPD, asthma and chronic, severe cough. The Company has three drugprogrammes, two of which are in Phase II. The lead programme, RPL554, is aninnovative dual phosphodiesterase (PDE) 3 and 4 inhibitor with bothbronchodilator and anti-inflammatory properties. VRP700 is an innovativeproduct for suppressing chronic, severe cough in patients with underlying lungdisease. In its third programme, Verona Pharma is investigating novelanti-inflammatory molecules, called NAIPs, for a wide range of respiratory andinflammatory 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 and asthma with bronchodilator and anti-inflammatory effects. Botheffects are essential to improve symptoms in patients with COPD or asthma.RPL554 is currently in phase II 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 market for COPD and asthma drugs is estimated to be £20 billion [source:visiongain]. About VRP700 for the treatment of Cough VRP700 is Verona Pharma's lead drug compound for the treatment of cough, havinga novel mechanism of action involving the suppression of cough initiatingsignals originating from cough sensory nerve endings located in the lungs. Aclinical trial completed at the University of Florence, Italy in September 2011clearly demonstrated significant anti-tussive effects with nebulised VRP700 inhospitalized patients with chronic severe cough. Cough can be a very debilitating comorbidity reported by patients, especiallythose with respiratory conditions such as asthma, COPD, lung cancer,interstitial lung disease, fibrosis or lung infections. It is a neglectedsymptom which is often self-medicated. Consumer spending on OTC medications,including those for cough, grew by 10% over 2005-10, to reach GBP532 million[source: Mintel]. However, there is very little clinical evidence for such OTCcough medications being really effective and it is widely recognised by themedical community that there is a large need for more effective drugs tocontrol and prevent pathologically induced coughing.