Verona Pharma Initiates Phase 2 Clinical Trial to Evaluate Dry Powder Inhaler Formulation of RPL554 for Maintenance Treatment of COPD

LONDON, Dec. 17, 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 the initiation of a Phase 2 clinical trial to evaluate the pharmacokinetic (“PK”) profile, efficacy and safety of a dry powder inhaler (“DPI”) formulation of RPL554 in patients with moderate to severe chronic obstructive pulmonary disease (“COPD”).

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 COPD, cystic fibrosis (“CF”) and asthma.

This randomized, double-blind, placebo-controlled, two-part study with the DPI formulation, being conducted at one site in the US, will enroll approximately 36 patients with COPD. The primary objective of the first part of the study is to evaluate the PK profile following a single dose of RPL554 when administered by DPI. Secondary objectives include evaluating the safety, tolerability and the bronchodilator effect of a single dose of RPL554 administered by DPI. The second part of the study, conducted as a multiple dose crossover study, will evaluate the bronchodilator effect of repeat doses of RPL554 administered by DPI in terms of peak forced expiratory volume in one second (“FEV₁”). Secondary objectives of this part of the study include evaluating the safety, tolerability and bronchodilator effect of repeat doses of RPL554 administered by DPI, as well as the PK profile, onset of action, and the amount of rescue medication use during treatment periods. Data from the single dose part of the study are expected during the first half of 2019.

RPL554 has been studied via the nebulized route of administration in 12 completed clinical trials involving more than 730 subjects. Verona Pharma has demonstrated in previous Phase 2 trials in patients with COPD that nebulized RPL554 significantly improves lung function, including improved peak FEV₁, reduced lung hyperinflation, and faster onset-of-action, when added to some of the most commonly used COPD treatments, including tiotropium, ipratropium, and albuterol. The studies also showed that RPL554 is well tolerated.

“Positive results using inhaler formulations could dramatically expand the clinical utility and commercial opportunity for RPL554 in the maintenance treatment of COPD and potentially broaden its use for other respiratory indications, such as asthma,” said Jan-Anders Karlsson, PhD, CEO of Verona Pharma. “With an estimated 5.4 million people using inhalers for the maintenance treatment of COPD in the US alone, and another one million patients using nebulized formulations, we believe it is important to understand how RPL554 works via these different delivery platforms in order to fully realize and leverage its clinical potential for patients with respiratory diseases.¹ We look forward to building upon the positive results that have been garnered to date utilizing the nebulized formulation of RPL554.”

In addition, Verona Pharma is currently conducting a Phase 2 clinical trial to evaluate nebulized RPL554 as an add-on treatment to dual LAMA/LABA therapy and triple LAMA/LABA/ICS therapy and also plans to evaluate RPL554 as a metered-dose inhaler (“MDI”) formulation as part of a comprehensive clinical program to fully demonstrate the clinical utility of RPL554 in improving the standard of care for COPD.

About Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (“COPD”) is a progressive and life-threatening respiratory disease for which there is no cure.² Although COPD is thought to be underdiagnosed, globally, around 384 million people suffer from the disease.³ 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.^2,[4] 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.² 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.⁵ 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 2020.⁶ 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.^7,8 There is an urgent need for drugs with novel mechanisms of action that can be used by these patients in addition to current therapies.

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^®), compared with such bronchodilators administered as a single agent. RPL554 improved FEV₁ 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 2b clinical trial.

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 final prospectus filed with the Securities and Exchange Commission (“SEC”) on April 28, 2017 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:

¹ Q2 2017 Verona US COPD physician survey research, Trends in COPD: Morbidity and Mortality, American Lung Association, 2013, Make et al, Intl. Journal of COPD, 2012
² World Health Organization. Chronic Obstructive Pulmonary Disease. http://www.who.int/mediacentre/factsheets/fs315/en/. Accessed September 2017.
³ 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.
⁴ World Health Organization. Burden of COPD. http://www.who.int/respiratory/copd/burden/en/. Accessed September 2017.
⁵ 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.
⁶ Centers for Disease Control. Increase Expected in Medical Costs for COPD. https://www.cdc.gov/features/ds-copd-costs/. Accessed September 2017.
7 Mullerova H., et al., Characterization of COPD Patients Treated With Inhaled Triple Therapy Containing Inhaled Corticosteroid [ICS], Long-Acting Beta2-Agonists [LABA], and Long-Acting Muscarinic Antagonists [LAMA] in the UK, American Journal of Respiratory and Critical Care Medicine 2017;195:A4986
8 Vestbo J, et al., Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINTY); a double-blind, parallel group, randomised controlled trial, The Lancet, Vol 389, p. 1919-1929; May 13, 2017.