Verona Pharma Reports Positive Top-Line Data from Phase 2a Trial with RPL554 in Cystic Fibrosis Patients

RPL554 demonstrates a favorable pharmacokinetic and pharmacodynamic profile in cystic fibrosis patients

LONDON, March 02, 2018 (GLOBE NEWSWIRE) -- Verona Pharma plc (AIM:VRP) (Nasdaq:VRNA) (“Verona Pharma”), a clinical-stage biopharmaceutical company focused on developing and commercializing innovative therapies for respiratory diseases, announces today that top-line data from its Phase 2a trial with nebulized RPL554 demonstrate that the investigational therapy has a favorable pharmacokinetic (PK) and pharmacodynamic (PD) profile, with single doses achieving statistically significant (P<0.05) increases in average forced expiratory volume in one second (FEV1) in patients with cystic fibrosis (CF). These data provide a solid foundation for further development of RPL554 for the treatment of CF.

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 CF. RPL554 has anti-inflammatory effects, and in pre-clinical studies, has been observed to stimulate the CF transmembrane conductance regulator (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.

“Achieving a six percent sustained improvement from baseline in FEV1 after a single dose is very impressive in this group of CF patients,” according to the trial’s lead investigator, Professor Andres Floto, Wellcome Trust Senior Investigator, and Research Director of the Department of Medicine, University of Cambridge and Papworth Hospital, UK.

“These top-line findings demonstrate a favorable pharmacokinetic profile of inhaled RPL554 in CF patients, which is consistent with our earlier findings in COPD,” said Jan-Anders Karlsson, PhD, CEO of Verona Pharma. “While we believe these results support further development of the drug in CF, we await the results of our ongoing Phase 2b trial for the maintenance treatment of COPD, for which we anticipate reporting top-line data early in the second quarter of 2018, to prioritize the future therapeutic focus of RPL554 development.

Trial details

This Phase 2a trial evaluated the PK and PD profile, and tolerability of RPL554 in 10 patients with CF, at 1.5 mg and 6.0 mg doses as compared to placebo. Patients displayed a range of CF genotype mutations in the CFTR.

Primary endpoint measure:

  • Pharmacokinetics of single nebulized doses of RPL554 in 10 patients with CF:
       -  The PK profile was consistent with that observed in patients with COPD, although with lower peak serum levels of RPL554 in CF patients; and
       -  Serum half-life was dose-dependent; 7.5 to 10.1 hours for 1.5 mg and 6 mg, respectively.

Secondary endpoint measures:

  • The drug also elicited a statistically significant increase in average FEV1 in treated patients for 1.5 mg (all P<0.01) and 6 mg (all P<0.05) at 4, 6 and 8 hour time points;   
  • The drug was well-tolerated in this patient group with an adverse event profile consistent with other studies with RPL554.

The 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.

“We’re pleased to see these interesting results come through, and that our investment in this area continues to show promise. We look forward to seeing the next steps of developing RPL554 for the treatment of cystic fibrosis” said Janet Allen, Director of Strategy and Innovation at the Cystic Fibrosis Trust.

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
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 treatment potential for RPL554, the results from the Phase 2a trial of RPL554 supporting further development of RPL554 in CF, the timing of data for the Phase 2b trial of RPL554 in COPD, the ability of RPL554 to address the urgent unmet medical need for therapeutics that treat in CF.

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, 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
Jan-Anders Karlsson, Chief Executive Officer
Tel: +44 (0)20 3283 4200

Stifel Nicolaus Europe Limited (Nominated Adviser and UK Broker)
Stewart Wallace / Jonathan Senior / Ben Maddison
Tel: +44 (0) 20 7710 7600

FTI Consulting (UK Media and Investor enquiries)
Simon Conway / Natalie Garland-Collins
Tel: +44 (0)20 3727 1000

ICR, Inc. (US Media and Investor enquiries)
James Heins
Tel: +1 203-682-8251

Stephanie Carrington
Tel. +1 646-277-1282