RPL554 clinical studies published in The Lancet RM

25 October 2013 Verona Pharma plc ("Verona Pharma" or the "Company") Clinical studies published in The Lancet Respiratory Medicine highlight RPL554 as a promising novel potential treatment for asthma and COPD Verona Pharma plc (AIM: VRP), the drug development company focused on"first-in-class" medicines to treat respiratory diseases, announces that a newresearch paper entitled "Efficacy and safety of RPL554, a dual PDE3 and PDE4inhibitor, in healthy volunteers and in patients with asthma or chronicobstructive pulmonary disease: findings from four clinical trials" is nowavailable on-line in The Lancet Respiratory Medicine.1 The peer-reviewed paperhighlights the potential of Verona Pharma's lead pipeline drug, RPL554, toreverse the narrowing and reduce the inflammation of airways quicker and withfewer side effects compared to current treatments. In summary, the results from four proof-of-concept clinical trials with RPL554showed that this novel dual PDE 3/4 inhibitor was well tolerated by healthysubjects, allergic asthmatics and patients with chronic obstructive pulmonarydisease (COPD). The drug showed a rapid and sustained bronchodilator activityat least as effective as the benchmark therapy salbutamol across a range ofdoses, along with a highly significant anti-inflammatory activity. Thesestudies demonstrate the importance of PDE3 in regulating airways tone inhealthy and diseased airways and the role of PDE4, possibly together with PDE3,in regulating airways inflammation. Verona Pharma is initially pursuingdevelopment of the drug in a nebulized format suitable for the treatment ofsevere COPD patients, a significant unmet medical need with few novelapproaches in clinical development. RPL554 is also suitable for incorporationinto dry powder inhaler (DPI) and pressurised metered dose inhaler (pMDI)devices, likely to be part of long-term development plans for the agent. Professor Clive Page, King's College London, study lead and Non-executiveChairman of Verona Pharma said, "These studies give us a glimpse into thepotential bronchodilator, bronchoprotective, and anti-inflammatory effects ofthis drug. So far trials have run for seven days or less and there is a need tolook at longer-lasting effects. Further studies are needed to better understandthe full potential of this new therapy for COPD and asthma." Dr Jan-Anders Karlsson, CEO of Verona Pharma commented, "The results detailedin The Lancet Respiratory Medicine, a highly respected medical journal,describe the large volume of clinical data that supports our furtherdevelopment of RPL554 as an effective new treatment option for patients withobstructive and inflammatory airways diseases. To the best of our knowledge,this drug is the first novel class of potent bronchodilator since the advent ofβ2-agonists and anti-cholinergic agents several decades ago. This, togetherwith its anti-inflammatory activity, confirms our intended initial positioningas a drug for severe COPD, a significant unmet medical need". In addition, a linked Comment will be published alongside the paper on Friday25 October. An audio interview with Professor Clive Page will appear on TheLancet Respiratory Medicine homepage, http://www.thelancet.com/journals/lanres/issue/current, on Monday 4 November. The full abstract of the paper can be accessed by following this weblink: http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(13)70187-5/abstract. Reference 1. Lui.G Franciosi, PhD, Prof. Zuzana Diamant, MD, Katharine H Banner, PhD,Rob Zuiker, MD, Nicoletta Morelli, MD Ingrid Kamerling, PhD, Marieke L. de Kam MSc, Prof. Jacobus Burggraaf, MD, Prof. Adam.F.Cohen, MD Prof. Mario Cazzola, MD, Luigino Calzetta, PhD, Prof.Dave Singh, MD, Domenico Spina, PhD, Prof Michael J.A. Walker, PhD and Prof.Clive P Page, PhD. Published Online in The Lancet Respiratory Medicine, October 25, 2013, http:// dx.doi.org/10.1016/S2213-2600(13)70187-5. For further information please contact: Verona Pharma plc Tel: 020 7863 3300 Clive Page, Chairman Jan-Anders Karlsson, CEO Richard Bungay, CFO WH Ireland Limited Tel: 020 7220 1666 Chris Fielding Nick Field FTI Consulting Tel: 020 7831 3113 Julia Phillips Simon Conway Notes to Editors About The Lancet Respiratory Medicine The Lancet Respiratory Medicine publishes news, views, research, and reviews inrespiratory medicine and critical care. The journal, which launched in March2013, offers fast track publication of selected research papers which can bepublished online within 8 weeks of submission. The Lancet Respiratory Medicinecovers a wide breadth and diversity of topics of interest to clinicians,specialists, and researchers in the field of respiratory and critical caremedicine. See http://www.thelancet.com/respiratory for more details. 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 currently estimated to be GBP20 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 inUK [source: Mintel]. However, there is very little clinical evidence for suchOTC cough 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.