Verona Pharma Reports Positive Interim Data with Ensifentrine Dry Powder Inhaler Formulation in First of Two-Part Phase 2 Clinical Trial in COPD

Single dose of ensifentrine DPI formulation produced statistically significant and clinically meaningful dose-dependent bronchodilator response and was well tolerated at all doses

Data support initiation of part 2 of study to evaluate effect of ensifentrine DPI formulation over one week of treatment

First study to show efficacy of DPI formulation; Delivery via DPI could dramatically expand the clinical utility and commercial opportunity for ensifentrine in COPD and asthma

LONDON, March 04, 2019 (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 positive interim efficacy and safety data from part one of a two-part Phase 2 clinical trial of a dry powder inhaler (“DPI”) formulation of ensifentrine in patients with moderate-to-severe chronic obstructive pulmonary disease (“COPD”). The positive data support initiation of the second part of the Phase 2 trial to evaluate the ensifentrine DPI formulation in patients with moderate-to-severe COPD over one week of twice-daily treatment.

In the first part of the trial, 37 patients with moderate-to-severe COPD received a single dose of one (out of five) dosage strengths of ensifentrine (150 µg, 500 µg, 1500 µg, 3000 µg, or 6000 µg) or placebo. Interim efficacy and safety data from this single dose study showed a statistically significant and clinically meaningful increase in lung function as measured by forced expiratory volume in one second (“FEV₁”), compared to placebo.

• Peak FEV₁ increased from baseline in a dose-dependent manner (ranging from 68 mL to 333 mL, p<0.05 for doses 1500 µg and above).
• Average FEV₁ 0-4 hours and 0-12 hours also showed a dose response and demonstrated durability of effect over the dosing interval (average FEV₁ 0-4h: ranging from 68 mL to 296 mL, p<0.05 for doses 500 µg and above; average FEV₁ 0-12h: ranging from 54 mL to 254 mL, p<0.05 for doses 1500 µg and above, supporting twice-daily dosing).
• Ensifentrine DPI formulation has been observed to be well tolerated at each dose with an adverse event profile similar to placebo.

“The large bronchodilator response, 12-hour duration of action and good tolerability observed with the DPI ensifentrine formulation in the first portion of this study are very encouraging and we look forward to proceeding with the second part to evaluate treatment over a one-week period,” said Jan-Anders Karlsson, PhD, CEO of Verona Pharma. “Positive data from this and future studies with inhaler formulations could dramatically expand the clinical utility and commercial opportunity for ensifentrine not only in the treatment of COPD, but potentially in other respiratory diseases such as asthma.”

An estimated 5.5 million people in the US alone use inhalers for the maintenance treatment of COPD.¹ Delivery of a DPI formulation of ensifentrine creates exciting new opportunities for combining ensifentrine with existing therapeutics delivered by handheld inhalers. The value of the COPD maintenance market delivered via inhaler devices in the US alone was approximately $6 billion in 2017.²

The second part of this Phase 2 trial evaluating DPI ensifentrine is a randomized, double-blind, placebo-controlled, multiple dose crossover study, conducted at one site in the US. Patients will be randomized to one of four dose levels (150 µg, 500 µg, 1500 µg, or 3000 µg) or placebo, administered twice daily over one week. All patients will receive each dose level and placebo over five seven-day treatment periods. The primary endpoint of bronchodilator effect of repeat doses of ensifentrine delivered via DPI will be assessed in terms of peak FEV₁. Secondary objectives of this part of the study include evaluating the safety, tolerability and bronchodilator profile of repeat doses of ensifentrine administered by DPI, as well as the pharmacokinetic profile. The full data from parts one and two are expected to be reported in the second half of 2019.

Ensifentrine, also known as RPL554, is an investigational first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4 designed to have bronchodilator as well as anti-inflammatory properties. Verona Pharma continues to advance the nebulized formulation of ensifentrine through Phase 2b clinical development and plans to initiate a Phase 2 clinical trial of a pressurised metered-dose inhaler (“pMDI”) formulation of ensifentrine in patients with COPD in the second quarter of 2019. Ensifentrine is also in development for cystic fibrosis and asthma.

About Verona Pharma plc and ensifentrine

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, ensifentrine, is an investigational first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4 that is designed to act as both a bronchodilator and an anti-inflammatory agent in a single compound. Ensifentrine has been studied via the nebulized route of administration in 13 completed clinical trials involving more than 800 subjects. The nebulized formulation of ensifentrine has been observed to result in significantly improved lung function, including improved peak FEV₁, reduced lung hyperinflation and faster onset-of-action when used alone or as an add on treatment to some of the most commonly used COPD treatments, including tiotropium (Spiriva^®), tiotropium/olodaterol fixed-dose combination, ipratropium, and albuterol. In addition, ensifentrine has shown anti-inflammatory effects in a standard challenge study with COPD-like inflammation in human subjects. Ensifentrine has been observed to be well tolerated in these trials. Verona Pharma is developing ensifentrine for the treatment of COPD, CF, and asthma.

About Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (“COPD”) is a progressive and life-threatening respiratory disease for which there is no cure.³ Although COPD is thought to be underdiagnosed, globally, around 384 million people suffer from the disease.⁴ 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.^4,5 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.⁴ 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.6 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 2020.7 Approximately 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), worsening symptoms and exacerbations.^8,9 There is an urgent need for new treatment options with novel mechanisms of action that can be used by these patients in addition to current therapies.

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 that the interim data support selection of doses for the second part of the Phase 2 clinical trial, inhaler formulations of ensifentrine could expand the clinical utility and commercial opportunity for ensifentrine, the design of clinical trials, the timing of initiating clinical trials and receipt of results from clinical trials, the need for new treatment options for COPD, ensifentrine as a first-in-class inhibitor, and projections regarding the mortality rate of, and medical costs related to, COPD.

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 ensifentrine, 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 ensifentrine, 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 ensifentrine, which could adversely affect our ability to develop or commercialize ensifentrine; potential delays in enrolling patients, which could adversely affect our research and development efforts; we may not be successful in developing ensifentrine for multiple indications; our ability to obtain approval for and commercialize ensifentrine 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 ensifentrine; and lawsuits related to patents covering ensifentrine 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.

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¹ Verona Pharma COPD Market Survey May 2018; Trends in COPD: Morbidity and Mortality, American Lung Association, 2013, Make et al, Intl. Journal of COPD, 2012
² IQVIA MIDAS Sales ’17, excluding SABA, SAMA
³ World Health Organization. Chronic Obstructive Pulmonary Disease. http://www.who.int/mediacentre/factsheets/fs315/en/. Accessed September 2017.
⁴ 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.
⁵ World Health Organization. Burden of COPD. http://www.who.int/respiratory/copd/burden/en/. Accessed September 2017.
⁶ 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.
⁷ Centers for Disease Control. Increase Expected in Medical Costs for COPD. https://www.cdc.gov/features/ds-copd-costs/. Accessed September 2017.
⁸ 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.
⁹ 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.