Ensifentrine delivery via MDI inhalers could dramatically expand clinical utility and commercial opportunity

Verona Pharma plc (AIM:VRP) (Nasdaq:VRNA) (“Verona Pharma”), a biopharmaceutical company focused on respiratory diseases, announces the initiation of a Phase 2 dose-ranging trial to evaluate the pharmacokinetic (“PK”) profile, efficacy and safety of a pressurized metered-dose inhaler (“MDI”) formulation of ensifentrine (RPL554) in patients with moderate-to-severe chronic obstructive pulmonary disease (“COPD”). Verona Pharma is also developing a dry powder inhaler (“DPI”) formulation of ensifentrine.

In the US, DPI/MDI handheld inhalers are the most widely used option for medication in COPD, where an estimated 5.5 million people use inhalers for COPD maintenance therapy.¹ This market was valued at approximately $6 billion in 2017.²

The Phase 2 trial using the MDI formulation has a randomized, double-blind, placebo-controlled, two-part design. The Company anticipates reporting data from the first part of the trial in the second half of 2019, with final data expected in the first quarter of 2020.

The first part of the trial will evaluate the PK profile following a single dose of ensifentrine over 5 dose cohorts (100 µg, 300 µg, 1000 µg, 3000 µg, 6000 µg) or placebo. Verona Pharma is aiming to enroll 36 patients with moderate-to-severe COPD at two sites in the UK. The safety, tolerability and the bronchodilation effect of ensifentrine will also be assessed.

The second part of the trial will be conducted as a multiple dose crossover trial. Patients will be randomized to up to 4 dose levels or placebo, with the ensifentrine MDI formulation dosed twice-daily over one week. All patients will receive each of the dose levels and placebo, over the seven-day treatment period. The primary endpoint is based on bronchodilation and will be assessed in terms of peak forced expiratory volume in one second (FEV1), a standard measure of lung function. Secondary objectives of this part of the trial include evaluating the safety, tolerability and the bronchodilator profile as well as the PK profile.

“We are excited to expand the ensifentrine portfolio with the MDI formulation for the treatment of patients with COPD. DPI and MDI inhaler formulations have the potential to expand dramatically the clinical utility and commercial opportunity of ensifentrine in the treatment of COPD,” said Jan-Anders Karlsson, PhD, CEO of Verona Pharma. “We plan to seek a strategic partner to develop and commercialize inhalers of ensifentrine to maximize the significant potential value from this opportunity.”

In addition to advancing the MDI and DPI formulations of ensifentrine into Phase 2 clinical development, Verona Pharma has also developed a nebulized formulation of ensifentrine, which is currently being evaluated in a Phase 2b clinical trial in moderate-to-severe COPD patients designed to inform dose selection for Phase 3 trials planned for 2020.

¹IQVIA Q4 2017

² Trends in COPD: Morbidity and Mortality, American Lung Association, 2013, Make et al, Intl. Journal of COPD, 2012

About COPD

COPD is a progressive and life-threatening respiratory disease without a cure. The World Health Organization estimates that it will become the third leading cause of death worldwide by 2030. The condition damages the airways and the lungs, leading to debilitating breathlessness that has a devastating impact on performing basic daily activities such as getting out of bed, showering, eating and walking. 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. About 800,000 US COPD patients on dual/triple inhaled therapy (LAMA/LABA +/- ICS) remain uncontrolled, experiencing symptoms that impair quality of life. These patients urgently need better treatments.

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, ensifentrine (RPL554), is a first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4 that has been shown to act as both a bronchodilator and an anti-inflammatory agent in a single compound. Nebulized ensifentrine is currently in Phase 2b clinical development for the maintenance treatment of COPD and is planned to enter Phase 3 trials for this indication in 2020. Verona Pharma plans a targeted US launch of the nebulized formulation, which is expected to benefit from a simplified Medicare Part B reimbursement process in the US. Verona Pharma may also develop ensifentrine for the treatment of cystic fibrosis and asthma.

Ensifentrine has shown significant and clinically meaningful improvements in both lung function and COPD symptoms, including breathlessness in prior Phase 2 clinical studies in patients with moderate-to-severe COPD. In addition, ensifentrine has further improved lung function and reduced lung volumes in patients taking standard short- and long-acting bronchodilator therapy, including maximum bronchodilator treatment with dual/triple therapy. Ensifentrine has been well tolerated in clinical trials involving more than 800 people to date.