RPL554 demonstrates airway anti-inflammatory activity

VERONA PHARMA PLC - RPL554 demonstrates airway anti-inflammatory activity

PR Newswire

London, March 5

Verona Pharma plc (VRP: London Stock Exchange) ("Verona Pharma", or the"Company"), the biotechnology company focused on developing novel treatmentsfor chronic respiratory diseases today announces the results of an exploratory,placebo-controlled, double-blind clinical trial designed to specificallyevaluate the anti-inflammatory properties of RPL554 in healthy subjectschallenged with an inhaled irritant. This dual PDE3/4 inhibitor is underdevelopment as a novel, first-in-class, inhaled treatment for COPD (chronicobstructive pulmonary disease) and asthma.

This exploratory study showed a statistically significant reduction of totalcells as well as in various types of inflammatory cells entering the airways inRPL554 treated, compared to placebo treated, subjects. The primary end pointchosen for this exploratory trial was a reduction in the proportion ofneutrophil cells, an inflammatory cell type recognised for its central role inCOPD and severe asthma, to total inflammatory cells in the sputum and secondaryendpoints included reductions in total inflammatory cell numbers. While therewas a strong trend in favour of the primary endpoint, the study narrowly missedreaching statistical significance even though there was a highly significantreduction in the absolute number of neutrophils. Importantly, there were alsostatistically highly significant reductions in various types of inflammatorycells entering the airways in RPL554 treated subjects, providing positiveevidence of the drug's anti-inflammatory effects.

The study also showed that the drug was well tolerated with adverse eventsbeing mild and not significantly different to placebo. Consistent with earlierclinical studies with RPL554, there was no evidence of cardiovascular orgastrointestinal side effects.

Verona Pharma is currently developing RPL554, in a nebulised form, as a novelbronchodilator to treat patients with severe COPD, a significant unmet medicalneed. Previous clinical trials conducted by the Company have demonstrated thatRPL554 is a potent bronchodilator with fast onset of action in both COPD andasthma patients. Near- to mid-term clinical development will focus on itsbronchodilator properties in more severe patients. The Board believes that thisfocussed development will accelerate shareholder value growth. It is intendedthat the drug's anti-inflammatory activity will be explored more fully in laterstudies to examine further the drug's potential as a dual bronchodilator andanti-inflammatory treatment for patients with respiratory disease.

Professor Dave Singh of the Medicines Evaluation Unit, University ofManchester, who was the Principal Investigator, commented, "RPL554 reduced thenumber of inflammatory cells in the airways of healthy volunteers, suggestingthat the drug may have important anti-inflammatory effects in patients withCOPD or asthma. Encouragingly, daily treatment with RPL554 for a week was verywell tolerated and continued to show significant bronchodilator activity".

Jan-Anders Karlsson, CEO of Verona Pharma, commented, "We are very excited bythe outcome of this trial. The demonstration of significant anti-inflammatoryactivity with RPL554, coupled with its pronounced bronchodilator effects, makesthis a unique drug with significant promise as a new treatment for patientswith COPD or asthma. Our near-term focus for the further development of RPL554is on exploring the drug's significant bronchodilator properties in treatingairway obstruction in patients with severe COPD, a disease with a significantunmet medical need. This promises to be the fastest way to bring RPL554 tomarket."

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About the anti-inflammatory trial

The clinical trial was conducted at the Medicines Evaluation Unit ("MEU") inManchester, UK. It was designed to test the anti-inflammatory properties ofRPL554 in healthy subjects in an experimental model of relevance to COPD. Thestudy was a randomised, double-blind, placebo-controlled study in which 21subjects were treated once daily for 6 consecutive days with inhaled RPL554before being challenged on the last day by an irritant agent that provokes aninflammatory response in their airways. The ability of RPL554 to reduce theamount of inflammation in the airways was measured. The primary endpoint of thetrial was a reduction in the percentage of neutrophils in sputum. Secondaryendpoints were a reduction in the absolute number of inflammatory cells. Thisparticular test resembles certain aspects of the airway inflammation inpatients with COPD and is a common step in the development of newanti-inflammatory medicines for this disease.

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[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.

About The Medicines Evaluation Unit

The Medicines Evaluation Unit ("MEU") is one of the UK's leading contractresearch organisations, working in collaboration with the University Hospitalof South Manchester. The MEU specialises in performing clinical trials (fromPhase I through to IV) in respiratory/inflammatory medicine and related areas.The MEU has an outstanding reputation for performing high quality clinicalresearch complying with UK Clinical Trials legislation and EU Directives.