ATS Tuesday Presentation

VERONA PHARMA PLC - ATS Tuesday Presentation

PR Newswire

London, May 21

Further clinical data highlighting the significant bronchodilator activity of

novel dual PDE3/4 inhibitor RPL554 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 further poster was presented on Tuesday 21 May as part of the scientificprogramme at American Thoracic Society (ATS) International Conference,Philadelphia, USA, 17-22 May 2013. The abstract for this poster is reproducedbelow.

[Poster Board # 315] RPL554, A Dual PDE3/4 Inhibitor, Is Well Tolerated AndMaintains Bronchodilator Activity When Administered By Inhalation ToMild-To-Moderate Allergic Asthmatics On 6 Consecutive Days, [Publication Page:A3875]

L. Franciosi, PhD1, R. Zuiker, MD, MBA2, I.M. Kamerling, MD2, J. Burgraaf, MD,PhD2, A. Cohen, MD, PhD2, M. Walker, PhD1, C. Page, PhD1

1London/UK, 2Leiden/NL

Rationale: RPL554, an inhaled dual phosphodiesterase 3/4 inhibitor, hasbronchodilator, bronchoprotective and anti-inflammatory properties inpre-clinical models of allergen-induced asthma. Single doses of nebulizedRPL554 in healthy subjects and allergic asthmatics were well tolerated andinduced substantial bronchodilation and bronchoprotection in the asthmatics.The present study assessed tolerability and consistency of bronchodilatorresponses to inhaled RPL554 given on 6 consecutive days.

Methods: In a single-blind randomised placebo study, 12 clinically stablemild-to-moderate allergic asthmatics males (age: 19-52 years; BMI: 20-27 kg/m2;FEV1: 2.9-5.1 Litres; FEV1: 75-104% pred. FVC: 4.2-7.0 Litres; FEV1/FVC:56-90%; PEF: 7.1-13 Litres; PC20Mch: 0.10-6.1 mg/mL) not requiring controllernor regular bronchodilator therapy were studied. The tolerability andbronchodilator effects of inhaled RPL554 given daily at 0.018 mg/kg for 6 dayswas investigated using standard safety measures (i.e., heart rate, bloodpressure and ECG), pharmacokinetics (i.e., Cmax, AUC, T1/2), and spirometry(i.e., FEV1, PEF) on days 1, 3 and 6 at the same time and compared to placebomeasured at day -1 only. Study medication was administered over a 10 minuteperiod by a calibrated electronic nebuliser and oro-nasal mask.

Results: The 6 days of treatment were well-tolerated with a few mild and shortlasting minor adverse events reported. The most frequent were headache,irritation of the larynx and dryness of the throat. Heart rate and bloodpressure did not change consistently with minor changes in heart rate anddiastolic blood pressures at day 6. RPL554 drug retained its effect on FEV1 andPEF over the whole treatment period. The maintained effectiveness of RPL554 wasshown by the maximum increases in FEV1, as compared with day-1 responses, werewhich were 555, 505 and 485 mL, respectively for days 1, 3 and 6. The onlystatistical difference was between days 1 and 6 (p=0.031 by Least SquaresMean), but the overall pattern was for a clearly maintained effect. The PEFvalues remained comparable over study days 1, 3 and 6. Pharmacokineticevaluation of concentrations of RPL554 in plasma showed limited, non-consistentchanges in terms of Cmax, AUC, T1/2, indicating no major changes in systemicaccumulation or metabolism.

Conclusions: In mild-to-moderate allergic asthmatics, daily doses of nebulisedRPL554 for 6 consecutive days were well-tolerated and produced consistentbronchodilation without any accumulation or altered systemic metabolism.

Am J Respir Crit Care Med 187;2013:A3875

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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.