Verona Pharma Announces Publication Of Key Paper On Rpl554 In Copd In The European Respiratory Journal

 
TIDMVRP 
 
 
   Publication demonstrates RPL554's significant bronchodilation effect, in 
both large and small airways, alone and when combined with currently 
used bronchodilators in COPD patients 
 
   LONDON, Sept. 06, 2018 (GLOBE NEWSWIRE) -- Verona Pharma plc (AIM: VRP) 
(Nasdaq: VRNA) ("Verona Pharma" or the "Company"), a clinical-stage 
biopharmaceutical company focused on developing and commercializing 
innovative therapies for respiratory diseases, today announced that the 
high-impact, peer reviewed European Respiratory Journal has published  a 
paper entitled "The short term bronchodilator effects of the dual PDE3 
and PDE4 inhibitor RPL554 in COPD" that provides full results from two 
positive Phase 2 clinical studies with RPL554.(*)  Results from these 
studies were previously reported by Verona Pharma on May 10, 2016 and 
September 7, 2017. RPL554 is the Company's lead first-in-class drug 
candidate that has a dual bronchodilator and anti-inflammatory mechanism 
of action. RPL554 has potential as an add-on therapy to improve lung 
function and reduce symptom severity in chronic obstructive pulmonary 
disease (COPD) patients whose disease is not being adequately managed by 
the current standard of care. 
 
   Highlights 
 
   Publication details results from two studies demonstrating that RPL554 
combined with standard short- and long-acting bronchodilators: 
 
 
   -- Causes a pronounced additional bronchodilator effect in both large and 
      small airways. 
 
   -- Reduces lung hyperinflation, considered a cause of breathlessness in COPD 
      patients. 
 
   -- Improves speed of onset of action when combined with standard 
      bronchodilators. 
 
 
   The first study detailed in the publication compared the short-term 
bronchodilator effects of nebulized RPL554 with that of the commonly 
used bronchodilators salbutamol (a short-acting beta-agonist) and 
ipratropium (a short-acting anti-muscarinic agent), as well as placebo, 
in patients with reversible COPD.  Additional bronchodilator effects 
when adding RPL554 on top of these agents was also measured. 
 
   The second study detailed the extent of any additional bronchodilation 
that is achievable, in this patient group, when adding RPL554 to 
tiotropium (the long-acting anti-muscarinic Spiriva(R) , one of the most 
commonly used drugs to treat COPD). In both studies, peak forced 
expiratory volume in one second (FEV(1) ) lung volumes and specific 
airway conductance (sGAW) were studied as the principle measures of 
airway function. In both studies RPL554 demonstrated a placebo like 
side-effect profile. 
 
   The statistically significant results from these studies clearly 
demonstrate that the bronchodilator effect of RPL554 in patients with 
reversible COPD is, at the very least, of similar magnitude as that of 
the commonly used bronchodilators studied, and that clinically 
meaningful additional bronchodilation could be achieved by adding RPL554 
to the treatment of patients with such drugs. The paper concludes that 
"...RPL554 provided additional bronchodilation, reduced gas trapping, 
improved airway conductance, and a more rapid onset of action when 
administered in combination with either a beta-2 agonist or muscarinic 
antagonist. These short-term bronchodilator studies provide support to 
further study RPL554 in longer term COPD studies focused on other 
endpoints including symptoms and exacerbations." 
 
   Jan-Anders Karlsson, PhD, CEO of Verona Pharma, said: "The statistically 
significant results from the two Phase 2 trials detailed in this 
important paper continue to highlight the potential and differentiated 
profile of RPL554 as an add-on therapy to improve lung function and 
reduce symptom severity in COPD patients whose disease is not being 
adequately managed by the current standard of care." 
 
   Dave Singh, M.D., Professor of Clinical Pharmacology and Respiratory 
Medicine, Medicines Evaluation Unit, University of Manchester, and 
Principal Investigator in these studies, added: "The results published 
in the European Respiratory Journal not only profile the significant 
effect of RPL554 on improving lung function in COPD patients when used 
alone or in combination with commonly used bronchodilators, but also its 
rapid onset of action, especially when used in combination." 
 
   Verona Pharma is currently conducting a Phase 2 clinical trial to 
evaluate RPL554 as an add-on treatment to dual LAMA/LABA therapy and 
triple LAMA/LABA/ICS therapy, as part of a comprehensive clinical 
program to fully demonstrate the clinical utility of RPL554 in improving 
the standard of care for COPD. These data will also support the planning 
of the RPL554 phase 3 program. 
 
   Paper Abstract in Full 
 
   Introduction: We investigated the short-term bronchodilator effects of 
RPL554 (an inhaled dual phosphodiesterase 3 and 4 inhibitor) combined 
with other bronchodilators in COPD patients with reversibility (>150 mL 
to short acting bronchodilators). 
 
   Methods: Study 1: six way placebo controlled crossover study (n=36) with 
single doses of RPL554 (6mg), salbutamol (200<MU>g), ipratropium 
(40<MU>g), RPL554 + salbutamol, RPL554 + ipratropium and placebo. Study 
2: three way crossover study (n=30) of tiotropium (18 <MU>g) combined 
with RPL554 (1.5 mg or 6mg) or placebo for 3 days. FEV(1) , lung volumes 
and sGaw were measured. 
 
   Results: Study 1; Peak FEV(1) change compared to placebo was similar 
with RPL554, ipratropium and salbutamol (means 223, 199 and 187 mL 
respectively). The peak FEV(1) was higher for RPL554 + ipratropium 
versus ipratropium (mean difference 94 mL, p<0.0001) and RPL554 + 
salbutamol versus salbutamol (mean difference 108 mL; p<0.0001). Study 2 
(day 3); both RPL554 doses caused greater peak FEV(1) effects than 
placebo. The average FEV(1) (0- 12h) increase was greater with RPL554 
6mg only versus placebo (mean difference 65 mL p=0.0009). In both 
studies, lung volumes and sGAW showed greater RPL554 combination 
treatment effects versus monotherapy. 
 
   Conclusion: RPL554 combined with standard bronchodilators caused 
additional bronchodilation and hyperinflation reduction. 
 
   About COPD 
 
   Chronic obstructive pulmonary disease ("COPD") is a progressive and 
life-threatening respiratory disease for which there is no cure.(1) 
Although COPD is thought to be underdiagnosed, globally, around 384 
million people suffer from the disease.(2) This number, according to the 
World Health Organization ("WHO"), is likely to increase in coming years, 
with estimates that COPD will become the third leading cause of death 
worldwide by 2030.(1,3) The condition damages the airways and the lungs, 
leading to persistent symptoms of breathlessness, impacting a person's 
daily life and their ability to perform simple activities such as 
walking a short flight of stairs or carrying a suitcase.(1) Many 
experience acute periods of worsening symptoms called 'exacerbations', 
often leading to emergency department visits or hospital admissions and 
are also associated with high mortality.(4) In the United States alone, 
the 2010 total annual medical costs related to COPD were estimated to be 
$32 billion and are projected to rise to $49 billion in 2020.(5) About 
30-40% of moderate to severe COPD patients on triple inhaled therapy 
(ICS/LAMA/LABA) remain uncontrolled and continue to experience airway 
obstruction (breathing difficulties), COPD symptoms and 
exacerbations.(6) There is an urgent need for drugs with novel 
mechanisms of action that can be used by these patients in addition to 
current therapies. 
 
   _______________ 
 
   (*) Singh D et al; Eur Respir J. 2018 Aug 30. pii: 1801074. 
https://doi.org/10.1183/13993003.01074-2018 
 
   About Verona Pharma plc and RPL554 
 
   Verona Pharma is a clinical-stage biopharmaceutical company focused on 
developing and commercializing innovative therapies for the treatment of 
respiratory diseases with significant unmet medical needs. Verona 
Pharma's product candidate, RPL554, is a first-in-class, inhaled, dual 
inhibitor of the enzymes phosphodiesterase 3 and 4 that acts as both a 
bronchodilator and an anti-inflammatory agent in a single compound. In 
previous clinical trials, RPL554 has been observed to result in 
bronchodilator effects when used alone or as an add-on treatment to 
other COPD bronchodilators. It has shown clinically meaningful and 
statistically significant improvements in lung function when 
administered in addition to frequently used short- and long-acting 
bronchodilators, such as tiotropium (Spiriva(R)), compared with such 
bronchodilators administered as a single agent. RPL554 improved FEV(1) 
over four weeks in patients with moderate-to-severe COPD when compared 
to placebo and improved COPD symptoms and Quality of Life in a Phase 2b 
multicenter European study performed in 403 patients. In addition, 
RPL554 has shown anti-inflammatory effects in a standard challenge study 
with COPD-like inflammation in human subjects. RPL554 has been well 
tolerated in these studies and has a favorable safety and tolerability 
profile, having been administered to more than 730 subjects in 12 
clinical trials. Verona Pharma is developing RPL554 for the treatment of 
chronic obstructive pulmonary disease ("COPD"), cystic fibrosis ("CF"), 
and potentially asthma. 
 
   Forward-Looking Statements 
 
   This press release contains forward-looking statements. All statements 
contained in this press release that do not relate to matters of 
historical fact should be considered forward-looking statements, 
including, but not limited to, statements regarding the design of the 
Phase 2 clinical trial of RPL554, the timing of availability of top-line 
data for the Phase 2 clinical trial, the importance of the Phase 2 
clinical trial to our development plans for RPL554, the potential of 
RPL554 as a promising first-in-class treatment option for COPD, and the 
value of the data and insights that may be gathered from the Phase 2 
clinical trial, including for the purpose of designing pivotal Phase 3 
trials. 
 

   These forward-looking statements are based on management's current 
expectations. These statements are neither promises nor guarantees, but 
involve known and unknown risks, uncertainties and other important 
factors that may cause our actual results, performance or achievements 
to be materially different from our expectations expressed or implied by 
the forward-looking statements, including, but not limited to, the 
following: our limited operating history; our need for additional 
funding to complete development and commercialization of RPL554, which 
may not be available and which may force us to delay, reduce or 
eliminate our development or commercialization efforts; the reliance of 
our business on the success of RPL554, our only product candidate under 
development; economic, political, regulatory and other risks involved 
with international operations; the lengthy and expensive process of 
clinical drug development, which has an uncertain outcome; serious 
adverse, undesirable or unacceptable side effects associated with 
RPL554, which could adversely affect our ability to develop or 
commercialize RPL554; potential delays in enrolling patients, which 
could adversely affect our research and development efforts and the 
completion of our Phase 2 trial; we may not be successful in developing 
RPL554 for multiple indications; our ability to obtain regulatory 
approvals necessary to conduct later stage trials and to commercialize 
RPL554 in multiple major pharmaceutical markets; misconduct or other 
improper activities by our employees, consultants, principal 
investigators, and third-party service providers; material differences 
between our "top-line" data and final data; our reliance on third 
parties, including clinical investigators, manufacturers and suppliers, 
and the risks related to these parties' ability to successfully develop 
and commercialize RPL554; and lawsuits related to patents covering 
RPL554 and the potential for our patents to be found invalid or 
unenforceable. These and other important factors under the caption "Risk 
Factors" in our Annual Report on Form 20-F filed with the Securities and 
Exchange Commission ("SEC") on February 27, 2018 relating to our 
Registration Statement on Form F-1, and our other reports filed with the 
SEC, could cause actual results to differ materially from those 
indicated by the forward-looking statements made in this press release. 
Any such forward-looking statements represent management's estimates as 
of the date of this press release. While we may elect to update such 
forward-looking statements at some point in the future, we disclaim any 
obligation to do so, even if subsequent events cause our views to 
change. These forward-looking statements should not be relied upon as 
representing our views as of any date subsequent to the date of this 
press release. 
 
   For further information, please contact: 
 
 
 
 
 
Verona Pharma plc                                  Tel: [phone] 
Jan-Anders Karlsson, Chief Executive Officer       [e-mail] 
 
Stifel Nicolaus Europe Limited (Nominated Adviser  Tel: [phone] 
 and UK Broker) 
Stewart Wallace / Jonathan Senior / Ben Maddison 
 
FTI Consulting (UK Media and Investor enquiries)   Tel: [phone] 
Simon Conway / Natalie Garland-Collins             [e-mail] 
 
ICR, Inc. (US Media and Investor enquiries) 
James Heins                                        Tel: [phone] 
                                                    [e-mail] 
Stephanie Carrington                               Tel. [phone] 
                                                    [e-mail] 
 
 
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