Verona Pharma plc Verona Pharma Presented Clinical Data At Ats 2018 That Further Highlights Rpl554 As A First-in-Class Treatm...

 
TIDMVRP 
 
 
   Achieved statistically significant and clinically meaningful additional 
improvement in peak lung function and faster onset-of-action in COPD 
patients with RPL554 when added to tiotropium 
 
   LONDON, May 22, 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 presented Phase 2a 
and pharmacokinetic data from two clinical trials evaluating its lead 
product candidate, RPL554, in chronic obstructive pulmonary disease 
(COPD) at the American Thoracic Society International Conference (ATS 
2018), in San Diego. Results from these trials were previously reported 
by Verona Pharma on September 7, 2017 
https://globenewswire.com/news-release/2017/09/07/1108710/0/en/Verona-Pharma-Announces-Positive-Top-Line-Data-from-Phase-2a-Clinical-Trial-in-COPD-with-RPL554-Dosed-in-Addition-to-Tiotropium-Spiriva.html 
and September 27, 2017 
https://globenewswire.com/news-release/2017/09/27/1133508/0/en/Verona-Pharma-Reports-Positive-Top-Line-Data-from-U-S-Pharmacokinetic-Trial-Demonstrating-Nebulized-RPL554-Delivers-Optimal-Clinical-Dose-to-Patients.html 
, respectively. 
 
   RPL554 is a first-in-class, inhaled, dual inhibitor of the enzymes 
phosphodiesterase 3 and 4 designed to have anti-inflammatory as well as 
bronchodilator properties, and is currently in development for the 
maintenance treatment of COPD and for the treatment of cystic fibrosis. 
 
   The poster, titled, "RPL554, A First-In-Class Dual PDE3/4 Inhibitor, 
Causes Rapid Additional Bronchodilation When Dosed with Tiotropium in 
COPD Patients," provided a review of the positive data from Verona 
Pharma's Phase 2a clinical trial, in which RPL554 was dosed in addition 
to tiotropium (Spiriva(R) ), one of the most commonly used drugs to 
treat COPD. In summary, the data from this Phase 2a trial demonstrated 
significantly improved peak lung function when RPL554 was added to 
tiotropium in patients with moderate-to-severe COPD. 
 
   This was a double blind, placebo-controlled, three way cross-over trial 
in 30 subjects with COPD and included two different doses of RPL554, 1.5 
mg and 6 mg, or placebo, dosed twice-daily for three days, in addition 
to tiotropium, a long-acting anti-muscarinic (LAMA) bronchodilator, 
dosed once-daily (ClinicalTrials.gov Identifier: NCT03028142). The 
primary outcome measures for the trial were peak forced expired volume 
in one second (FEV(1) ) on the third day of dosing and the average 
FEV(1)  on the third day of dosing, representing measures of lung 
function and duration of effect. A number of secondary outcome measures 
were also recorded. Of note, the 6 mg dose of RPL554 achieved 
statistical significance, compared to placebo, on all primary and 
secondary outcome measures. The data confirmed dose dependency between 
the two RPL554 doses. 
 
   Highlights 
 
 
   -- Primary outcome measures1:  -- RPL554, compared to placebo, produced a 
      statistically significant (1.5 mg, p=0.002; 6 mg, p<0.001) and a 
      clinically meaningful (>100 ml) peak FEV1 on the third day of dosing 
      (additional bronchodilation) when administered on top of the standard 
      bronchodilator, tiotropium (Spiriva(R))  -- Average FEV1 on the third day 
      of dosing (0 - 12 hours) of RPL554 when added on top of tiotropium was 
      larger than that of tiotropium alone (1.5 mg, p=0.099; 6 mg, p<0.001) 
 
   -- Secondary outcome measures:  -- Both doses of RPL554 produced a 
      statistically significant faster onset of action2 (1.5 mg, 4.2 min; 6 mg, 
      4.6 min) when added to tiotropium compared to tiotropium alone (37.6 min; 
      p<0.001)  -- The administration of RPL554 as an add-on treatment to 
      tiotropium caused a marked reduction in Functional Residual Capacity (1.5 
      mg, p<0.01; 6 mg, p<0.05) and in Residual Volume (1.5 mg, p=0.07; 6 mg, 
      p<0.01), both measures of trapped air in the lung, as compared to 
      tiotropium alone     - Suggesting that RPL554 treatment may reduce 
      dyspnea, a major debilitating symptom of COPD3. 
 
   -- Both doses of RPL554 were well tolerated as add-on treatments to 
      tiotropium:  -- Adverse reactions were consistent with previous studies 
      with RPL554 and tiotropium. No cardiovascular-related or gastrointestinal 
      related adverse reactions were reported. 
 
   __________________________ 
 
   (1)  In the study, a p-value<0.05 is regarded as statistically 
significant 
 
   (2)  Defined as FEV(1)  improvement by greater than or equal to 10% 
 
   In addition, Verona Pharma presented data at ATS from its 
pharmacokinetic trial with RPL554 in a poster titled, "Low Oral 
Bioavailability of RPL554, a First-in-Class Dual PDE3/4 Inhibitor, 
Demonstrates that its Nebulized, Inhaled Formulation is Appropriate for 
Delivering Optimal Pulmonary Dose," which showed that inhaled RPL554 is 
an appropriate form of administration for patients with COPD and other 
respiratory disorders. 
 
   This complete block two-way crossover trial evaluated a single dose of 
RPL554 in 12 healthy volunteers to determine the process of bodily 
absorption, distribution, metabolism and excretion of this novel therapy, 
including the swallowed portion of the nebulized dose. The trial was 
conducted under an Investigational New Drug application accepted by the 
U.S. Food and Drug Administration in June 2017. 
 
   With any inhaled or nebulized medication, a portion of the substance is 
deposited in the mouth and then swallowed by the patient. These results 
showed that in the study subjects, only 10.4 percent of the inhaled dose 
entered the bloodstream via the gastrointestinal tract. The low oral 
bioavailability of nebulized RPL554, as demonstrated in the study, is 
consistent with optimal inhaled delivery of medications for the 
treatment of COPD and asthma. Therefore, the results from this study 
confirmed that inhaled RPL554 is an appropriate form of administration 
for patients. 
 
   Dave Singh, M.D., Professor of Clinical Pharmacology and Respiratory 
Medicine, Medicines Evaluation Unit, University of Manchester, presented 
the RPL554 with tiotropium data at ATS and commented, "These encouraging 
data warrant further investigation of RPL554 to meet the urgent need for 
drugs with novel mechanisms of action that can be used in addition to 
current therapies, in order to provide further treatment of both COPD 
symptoms and exacerbations." 
 
   "These positive data are further evidence of RPL554's promising 
therapeutic potential for the treatment of COPD patients, further 
supporting Verona's ongoing clinical development program," said 
Jan-Anders Karlsson, PhD, CEO of Verona Pharma. "We look forward to 
advancing development of this first-in-class treatment this year by 
initiating in the third quarter a Phase 2a clinical trial to evaluate 
RPL554 when dosed in addition to LAMA/LABA therapy or triple therapy, 
compared to placebo. We also plan this year to complete pre-clinical 
studies for RPL554 delivered as both pressurized metered dose inhaler 
and dry powder inhaler formulations, followed by clinical trials in 
healthy subjects or patients with COPD targeted to commence in the first 
quarter of 2019." 
 
   In March 2018, the Company reported positive top-line results from a 
Phase 2b trial for the maintenance treatment of COPD. The study met its 
primary endpoint, with RPL554 producing a clinically and statistically 
significant improvement in FEV(1)  at four weeks in patients with 
moderate-to-severe COPD compared to placebo. Furthermore, the peak 
FEV(1)  was significantly improved at all time points over the four 
weeks of dosing. Secondary endpoints measuring 12 hour average FEV(1) , 
progressive improvement in COPD symptoms and Quality of Life were also 
met and support the potential clinical benefits of RPL554 for the 
treatment of COPD. RPL554 was well tolerated at all doses with an 
adverse event profile similar to placebo. 
 
   (__________________________) (3)  Dyspnea (shortness of breath) in COPD 
patients is often associated with hyperinflation of the lungs resulting 
from a higher residual volume of air 
 
   About COPD 
 
   Chronic obstructive pulmonary disease (COPD) is a progressive and 
life-threatening respiratory disease for which there is no cure.(1)  The 
condition damages the airways and the lungs, leading to persistent 
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)  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)  Current COPD therapies 
focus on reducing and controlling symptoms. Yet, despite the wide 
availability of these treatments, many patients continue to suffer acute 
periods of worsening symptoms known as exacerbations. These 
exacerbations often lead 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 Verona Pharma plc 
 
   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 
clinical trials, treatment with RPL554 has been observed to result in 
statistically significant improvements in lung function as compared to 

placebo, and has shown clinically meaningful and statistically 
significant improvements in lung function when administered in addition 
to frequently used short- and long-acting bronchodilators as compared to 
such bronchodilators administered as a single agent. 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 value of the 
results from the Phase 2a and pharmacokinetic clinical trials, RPL554 as 
a new complementary treatment for patients with COPD, projected annual 
medical costs related to COPD, the results of the Phase 2a and 
pharmacokinetic trials supporting later stage development of RPL554, the 
future clinical development and positioning of RPL554, and the treatment 
potential for RPL554. 
 
   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; we may not 
be successful in developing RPL554 for multiple indications; our ability 
to obtain approval for and 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. 
 
   __________________________ 
 
   (1)  World Health Organization. Chronic Obstructive Pulmonary Disease. 
http://www.who.int/mediacentre/factsheets/fs315/en/. Accessed September 
2017. 
 
   (2)  Adeloye D, Chua S, et al. Global and regional estimates of COPD 
prevalence: Systematic review and meta-analysis. J Glob Health 2015; 
5(2): 020415. 
 
   (3)  World Health Organization. Burden of COPD. 
http://www.who.int/respiratory/copd/burden/en/. Accessed September 2017. 
 
   (4)  COPD Foundations. Characteristics of COPD Patients Using United 
States Emergency Care or Hospitalization. 
https://journal.copdfoundation.org/jcopdf/id/1103/Characteristics-of-COPD-Patients-Using-United-States-Emergency-Care-or-Hospitalization. 
Accessed September 2017. 
 
   (5)  Centers for Disease Control. Increase Expected in Medical Costs for 
COPD. https://www.cdc.gov/features/ds-copd-costs/. Accessed September 
2017. 
 
 
 
   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             veronapharma@fticonsulting. 
                                                    com 
 
 ICR, Inc. (US Media and Investor enquiries) 
 James Heins                                        Tel: [phone] 
                                                    [e-mail] 
 Stephanie Carrington                               Tel. [phone] 
                                                    Stephanie.Carrington@icrinc 
                                                    .com 
 
 
 
   This announcement is distributed by Nasdaq Corporate Solutions on behalf 
of Nasdaq Corporate Solutions clients. 
 
   The issuer of this announcement warrants that they are solely 
responsible for the content, accuracy and originality of the information 
contained therein. 
 
   Source: Verona Pharma plc via Globenewswire 
 
 
  http://www.veronapharma.com/ 
 

(END) Dow Jones Newswires

May 22, 2018 02:03 ET (06:03 GMT)

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