Verona Pharma plc Data From Clinical And Pre-Clinical Trials Evaluating Verona Pharma's Rpl554 In Cystic Fibrosis Presented A...

 
TIDMVRP 
 
   Pre-clinical findings show RPL554 stimulates rare class III and IV CFTR 
mutants 
 
   Phase 2a results demonstrate RPL554 has favorable pharmacokinetic and 
pharmacodynamic profile in cystic fibrosis patients 
 
   LONDON, Oct. 26, 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, announce the presentation 
of positive data from pre-clinical and Phase 2a trials evaluating RPL554 
as a potential treatment for cystic fibrosis ("CF") at the 2018 North 
American Cystic Fibrosis Conference in Denver, CO. Data from the trials 
show that RPL554 stimulates rare Class III and Class IV cystic fibrosis 
transmembrane conductance regulator ("CFTR") mutants and that RPL554 has 
a favorable pharmacokinetic ("PK") profile and increased forced 
expiratory volume in one second ("FEV1") among patients with CF, 
respectively. Top-line data from this Phase 2a trial were previously 
reported by Verona Pharma on March 2, 2018 
https://www.globenewswire.com/Tracker?data=vhfDfMySvp6Jew3jB8yyKCRtogdF82p6Mgabwf8NLcjPvCly-xFcQHDzEMcfRT-57BXMxONw4ZFSjXeQqFfE233qiJoJSJMUr1pwsIpeFqWj9ffcEp9Gea3XhQyodBeshUTPh5hVrah_4dvQBG22WOZFd-oZ-tSWVIyphgISXzbo1oLWQRRCrZM6ZmGZ4qw7VCpBqylVI9ZBYC2-IJOuIbybj0r5xm-MP1_05lyoRMSSJp3MyGs7lTz7pyVG-SuDc8VzY6McWHqNZvgompeAmw== 
. 
 
   RPL554 is a first-in-class, inhaled, dual inhibitor of the enzymes 
phosphodiesterase 3 and 4 designed to have bronchodilator as well as 
anti-inflammatory properties, and is currently in development for the 
maintenance treatment of chronic obstructive pulmonary disease ("COPD") 
and for the treatment of CF. In pre-clinical studies, RPL554 has been 
observed to stimulate the CFTR, a protein whose mutation results in 
dysfunctional ion channels in epithelial cells, leading to CF. Based on 
available data, RPL554 has the potential to enhance mucociliary 
clearance (reduce phlegm in the airways), reduce airway obstruction and 
inhibit inflammation. 
 
   Pre-clinical data presented at the meeting show that RPL554 
significantly enhanced activity in cells that expressed T338I and R334W 
CFTR mutants, demonstrating that RPL554 alone positively regulates these 
CFTR mutants, which is consistent with previous findings in cells 
expressing the R117H mutation. In addition, when cells expressing S549R 
and G551D mutants were pretreated with VX809 (Orkambi(R) ) for 24 hours, 
RPL554 further enhanced CFTR-dependent activity, indicating that RPL554 
can stimulate rare Class III and Class IV mutants when administered 
alone or in combination with Orkambi(R) and has the potential to benefit 
patients who possess a wide range of different CFTR mutations. Results 
from the pre-clinical trial were presented by Mark Turner, PhD, 
Postdoctoral Research Fellow, Cystic Fibrosis Translational Research 
Centre (CFTRc), McGill University. 
 
   As part of the Phase 2a trial results presented, a single dose of 
nebulized RPL554 administered to 10 patients with CF demonstrated a PK 
profile that was consistent with that observed in patients with COPD in 
previous trials. Furthermore, RPL554 demonstrated a statistically 
significant increase in average FEV(1) in patients treated with 1.5 mg 
(all p<0.01) and 6 mg (all p<0.05) at four, six and eight hour time 
points. Results from the Phase 2a trial were authored by Odiri Eneje, MD, 
Clinical Fellow, Department of Thoracic Medicine, Papworth Hospital NHS 
Foundation Trust. This trial was conducted at Papworth Hospital, UK, one 
of the largest specialist cardiothoracic hospitals in Europe, and was 
supported by the UK Cystic Fibrosis Trust pursuant to the second Venture 
and Innovation Award received by Verona Pharma in October 2016. 
 
   Abstracts included as part of the 2018 NACFC program have been published 
in the September 2018 issue of the supplement to Pediatric Pulmonology 
(Volume 53, Issue S2), which can be found online 
https://www.globenewswire.com/Tracker?data=Mj_jhi3izX5Ix-KTgWpA3WpKMQUAnh3qPnCbaQ3DbqKRTFaq90gpcS8r5B09-O-_yRl80almfbeltqgFtjbEzl7HkdojIcVO17IUleQntImr5N1GD9ljhf4XMVejvJx2 
here. 
 
   "The potential for RPL554 to stimulate numerous rare class III and IV 
CFTR mutations is an important advancement for CF patients as it 
highlights RPL554 as a novel therapeutic. Current FDA-approved therapies 
are limited in their ability to address this need for patients," said 
Dr. Turner. 
 
   "We are encouraged by the positive data being accrued from pre-clinical 
and clinical studies with RPL554 in both CF and COPD," said Jan-Anders 
Karlsson, PhD, CEO of Verona Pharma. "RPL554 has been well-tolerated and 
demonstrated bronchodilator and anti-inflammatory activity in our 
extensive COPD clinical trial program and we are encouraged that this 
dual effect also shows promise in CF. There remains a high unmet need 
among CF patients to address inflammation which is known to cause 
disease progression and can lead to worsening of symptoms as well as 
pulmonary exacerbations." 
 
   Verona Pharma has demonstrated in previous Phase 2 trials in patients 
with COPD that RPL554 significantly improves lung function, including 
improved peak lung function, reduced lung hyperinflation, and faster 
onset-of-action, when added to some of the most commonly used COPD 
treatments, including tiotropium, ipratropium, and albuterol. 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 COPD program. 
 
   About Cystic Fibrosis 
 
   CF is the most common fatal inherited disease in the United States and 
Europe. CF causes impaired lung function and is commonly associated with 
repeat and persistent lung infections due to the inability to clear 
thickened mucus from the lung. This condition often results in frequent 
exacerbations and hospitalizations. There is no cure for CF and the 
median age of death for CF patients is around 40 years. CF is considered 
a rare, or orphan, disease by both the U.S. Food and Drug Administration 
and the European Medicines Agency. According to the Cystic Fibrosis 
Foundation, more than 30,000 people in the United States and more than 
70,000 people worldwide are living with CF and approximately 1,000 new 
cases of CF are diagnosed each year. CF patients require lifelong 
treatment with multiple daily medications, frequent hospitalizations and, 
ultimately, lung transplants in some end-stage patients. The quality of 
life for CF patients is compromised as a result of spending significant 
time on self-care every day and frequent outpatient doctor visits and 
hospitalizations. CF patients take an average of seven medications 
daily. 
 
   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 treatment 
potential for RPL554, the results of the Phase 2a trial of RPL554 
supporting the further development of RPL554 in CF, 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 CF, 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: +44 (0) 20 
 and UK Broker)                                     7710 7600 
Stewart Wallace / Jonathan Senior / Ben Maddison 
 
FTI Consulting (UK Media and Investor enquiries)   Tel: [phone] 
                                                    1000 
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] 
 
 
 
 
 
 

(END) Dow Jones Newswires

October 26, 2018 05:12 ET (09:12 GMT)

Copyright (c) 2018 Dow Jones & Company, Inc.