Verona Pharma PLC Positive results from RPL554 dose-finding study

 
TIDMVRP 
 
Verona Pharma plc 
 
                      ("Verona Pharma" or the "Company") 
 
     Verona Pharma reports positive results from RPL554 dose-finding study 
 
  Study demonstrates drug has substantial bronchodilator effect and excellent 
                     tolerability at broad range of doses 
 
 Data continues to suggest drug could be meaningful new addition, alone or in 
                    combination, for the treatment of COPD 
 
15 March 2016, Cardiff - Verona Pharma plc (AIM: VRP.L), the drug development 
company focused on first-in-class medicines to treat respiratory diseases, 
today announces positive headline data from a Phase IIa dose-finding clinical 
study using the Company's new proprietary nebulised formulation of RPL554. 
RPL554 is a novel inhaled PDE3/PDE4 inhibitor with both bronchodilator and 
anti-inflammatory properties in the same molecule, currently in development as 
a nebulised treatment for acute exacerbations in chronic obstructive pulmonary 
disorder (COPD) patients in a hospital or home-care setting. Such patients 
typically require additional bronchodilation as well as anti-inflammatory 
treatment despite being on maximum doses of approved COPD medications (which 
often contain salbutamol). 
 
Highlights 
 
  * Primary objective of study met 
 
      + Nebulised RPL554 demonstrated a dose-dependent bronchodilator response 
        in asthma patients; the response was highly statistically significant 
        (p<0.0001) at all doses tested1 
 
  * The maximum bronchodilator effect of RPL554 in this study was comparable to 
    the effect observed with the supramaximal dose (7.5mg) of nebulised 
    salbutamol used in this study2 
 
  * RPL554 did not elicit any serious adverse events or adverse events of 
    concern at any dose 
 
      + Large dose range (0.4 to 24mg) examined; suggests RPL554 potentially 
        has a very large safety margin 
 
      + Fewer adverse events recorded with RPL554 than with nebulised 
        salbutamol 
 
      + No gastro-intestinal adverse events or cardiovascular events of concern 
 
  * We continue to expect a Phase II clinical study examining nebulised RPL554 
    as an add-on treatment to standard bronchodilators to report top-line data 
    in Q2 2016 
 
Dr Jan-Anders Karlsson, the CEO of Verona Pharma, said: 
 
"We are very excited by the results from our dose-finding study for RPL554. It 
is very pleasing that the maximum bronchodilator effect of RPL554 is comparable 
to that seen with the highest dose of salbutamol used in the study - a dose 
equivalent to the highest dose of salbutamol used to treat acute exacerbations 
of COPD in the emergency department - it is noteworthy that this was achieved 
with fewer adverse events. The data generated in this study emphasises its 
pronounced bronchodilator effect, and combined with its unique 
anti-inflammatory effects, we continue to believe that RPL554 could be an 
important, and much needed, new treatment option, either alone or as an add-on 
to existing drugs, for patients with COPD." 
 
Professor Leif Bjermer of Skane University, Lund, Sweden, lead investigator on 
this study, commented: 
 
"This well-designed and successfully executed dose-ranging study of nebulised 
RPL554 in moderate asthmatics demonstrated the drug has a linear and thus 
predictable pharmacokinetic profile, and produced similar bronchodilation but 
with less side effects compared to a very high dose of salbutamol, used as a 
comparator. The drug was well tolerated, and few adverse events were recorded. 
Together, this suggests that the drug could have a large therapeutic index. 
With further clinical testing, RPL554 could become an important, and much 
needed novel treatment option, for patients with COPD and other airway's 
disease." 
 
The intent of the study was to demonstrate a dose-dependent bronchodilator 
effect of RPL554 and compare to nebulised salbutamol. In the hospital setting, 
the usual starting nebulised dose of salbutamol is 2.5mg but occasionally up to 
3 times this dose (7.5mg) is used to produce additional bronchodilation in 
severely ill patients. We compared RPL554 to both the standard dose and the 
very high dose of salbutamol to evaluate maximum bronchodilator effects and 
tolerability. 
 
In this randomised, double-blind, placebo-controlled, seven way crossover Phase 
IIa study, 29 patients with mild to moderate persistent asthma each received 
four doses of nebulised RPL554 (0.4 to 24 mg), as well as two doses of 
nebulised salbutamol (2.5mg and 7.5mg), or placebo. In addition to the largest 
dose tested in previous studies (24mg), lower doses of the new proprietary 
nebulised formulation of RPL554 than had been used before, were explored to 
identify a minimally effective dose. The study was performed at Celerion 
(Belfast, Ireland) and Skane University Hospital (Lund, Sweden). 
 
The study met its primary objective, with nebulised RPL554 demonstrating a 
dose-dependent bronchodilator response in asthma patients. RPL554 
pharmacokinetics were linear across the whole dose range. At the highest doses 
of both compounds, RPL554 produced the same maximum bronchodilator effect as 
salbutamol. Even the lowest RPL554 dose of 0.4mg was significantly superior (p 
<0.0001) to placebo as a bronchodilator. All doses of RPL554 were found to be 
well tolerated and the data supports the use of RPL554 in a twice daily dosing 
regimen. There were no reports of serious adverse events and fewer adverse 
events were seen with RPL554 than with salbutamol. Salbutamol produced 
well-acknowledged adverse events for this drug including tremor, tachycardia, 
palpitations, and a reduction in blood potassium levels. The large dosing range 
(60 fold) of RPL554 suggests a potentially large therapeutic index. 
 
RPL554 is currently in development as a nebulised treatment for acute 
exacerbations in COPD patients in a hospital or home-care setting. The data 
from the study reported today will help inform dose selection in the Phase IIb 
trial, which it is currently expected to commence in early 2017. 
 
The nebuliser bronchodilator market was worth about $1 billion in 2014 in the 
US.3 RPL554 has potential as a novel drug for the maintenance therapy of COPD, 
and for patients with asthma and cystic fibrosis. 
 
References 
 
1 The study was carried out in asthmatics as typically a dose response 
relationship to bronchodilators can be more accurately established in this 
group of patients, compared to COPD patients 
 
2 Salbutamol is probably the most effective and widely used bronchodilator in 
asthma and COPD patients. The typical nebulised salbutamol dose range is 2.5mg 
and sometimes 5mg. A 7.5mg dose of nebulised salbutamol is sometimes used to 
treat acute exacerbations of COPD or asthma in the emergency department = a 
supramaximal dose 
 
3 IMS Consulting Group market research 2014 
 
                                    -Ends- 
 
For further information please contact: 
 
Verona Pharma plc                      Tel: +44 (0)20 7863 3300 
 
Jan-Anders Karlsson, CEO 
 
N+1 Singer                             Tel: +44 (0)20 7496 3000 
 
Aubrey Powell / Jen Boorer 
 
FTI Consulting                         Tel: +44 (0)20 3727 1000 
 
Simon Conway / Julia Phillips 
 
Notes to Editors 
 
About Verona Pharma plc 
 
Verona Pharma plc is a UK-based clinical stage biopharmaceutical company 
focused on the development of innovative prescription medicines to treat 
respiratory diseases with significant unmet medical needs, such as chronic 
obstructive pulmonary disease (COPD), asthma and cystic fibrosis. 
 
Verona Pharma's lead drug, RPL554, is a first-in-class drug currently in Phase 
2 trials as a nebulised treatment for acute exacerbations of COPD in the 
hospital setting. The drug is a dual phosphodiesterase (PDE) 3/4 inhibitor and 
therefore has both bronchodilator and anti-inflammatory effects, which are 
essential to the improvement of patients with COPD and asthma. 
 
Verona Pharma is also building a broader portfolio of RPL554-containing 
products to maximise its benefit to patients and its value.  This includes the 
very significant markets for COPD and asthma maintenance therapy.  In addition, 
the Company is exploring the potential of the drug in different diseases, such 
as cystic fibrosis, where it is in pre-clinical testing and has received a 
Venture and Innovation Award from the UK Cystic Fibrosis Trust. 
 
About Lung and Allergy, Clinical Trial Unit (CTU), Skane University Hospital, 
Lund, Sweden 
 
The Lung and Allergy clinical trial unit at Skane (http://www.akcsyd.se/ 
forskning/provningsenheten) has been working mainly with early phase II and III 
studies in Asthma and or COPD for 10 years. The CTU is a part of an academic 
respiratory research network group run by Professor Leif Bjermer, a recognised 
expert in this field. The scientific work is focused on disease mechanisms in 
asthma and COPD, identifying and validating potential new treatment targets by 
means of invasive and non-invasive techniques, advanced histology, cell and 
molecular biology. The CTU is equipped with a complete respiratory physiology 
lab with a special focus on techniques that can address small airway pathology. 
Biomarkers, biogenetics and functional imaging is also part of the explorative 
profile. Invasive studies with bronchoscopy, biopsies, brushing and lavage are 
also performed. 
 
About Celerion Belfast- Center of Excellence for Respiratory (www.celerion.com) 
 
Celerion is a member of the UK's Translational Research Partnership in 
Respiratory which is a unique cooperative of internationally leading clinicians 
and scientists whose aim is to improve the speed of developing innovative 
therapies for respiratory diseases by working in collaboration with research 
groups of the pharmaceutical industry. They have been recognized for their 
excellence in basic and translational research in respiratory medicine. 
 
About Chronic Obstructive Pulmonary Disease (COPD) 
 
Sixty-five million people worldwide suffer from moderate to severe COPD and the
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