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Data from Clinical and Pre-Clinical Trials Evaluating Verona Pharma’s RPL554 in Cystic Fibrosis Pres

Pre-clinical findings show RPL554 stimulates rare class III and IV CFTR mutants

Phase 2a results demonstrate RPL554 has favorable pharmacokinetic and pharmacodynamic profile in cystic fibrosis patients

LONDON, Oct. 26, 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, announce the presentation of positive data from pre-clinical and Phase 2a trials evaluating RPL554 as a potential treatment for cystic fibrosis ("CF") at the 2018 North American Cystic Fibrosis Conference in Denver, CO. Data from the trials show that RPL554 stimulates rare Class III and Class IV cystic fibrosis transmembrane conductance regulator ("CFTR") mutants and that RPL554 has a favorable pharmacokinetic ("PK") profile and increased forced expiratory volume in one second ("FEV1") among patients with CF, respectively. Top-line data from this Phase 2a trial were previously reported by Verona Pharma on March 2, 2018.

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 chronic obstructive pulmonary disease ("COPD") and for the treatment of CF. In pre-clinical studies, RPL554 has been observed to stimulate the 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.

Pre-clinical data presented at the meeting show that RPL554 significantly enhanced activity in cells that expressed T338I and R334W CFTR mutants, demonstrating that RPL554 alone positively regulates these CFTR mutants, which is consistent with previous findings in cells expressing the R117H mutation. In addition, when cells expressing S549R and G551D mutants were pretreated with VX809 (Orkambi®) for 24 hours, RPL554 further enhanced CFTR-dependent activity, indicating that RPL554 can stimulate rare Class III and Class IV mutants when administered alone or in combination with Orkambi® and has the potential to benefit patients who possess a wide range of different CFTR mutations. Results from the pre-clinical trial were presented by Mark Turner, PhD, Postdoctoral Research Fellow, Cystic Fibrosis Translational Research Centre (CFTRc), McGill University.

As part of the Phase 2a trial results presented, a single dose of nebulized RPL554 administered to 10 patients with CF demonstrated a PK profile that was consistent with that observed in patients with COPD in previous trials. Furthermore, RPL554 demonstrated a statistically significant increase in average FEV1 in patients treated with 1.5 mg (all p<0.01) and 6 mg (all p<0.05) at four, six and eight hour time points. Results from the Phase 2a trial were authored by Odiri Eneje, MD, Clinical Fellow, Department of Thoracic Medicine, Papworth Hospital NHS Foundation Trust. This 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.

Abstracts included as part of the 2018 NACFC program have been published in the September 2018 issue of the supplement to Pediatric Pulmonology (Volume 53, Issue S2), which can be found online here.

"The potential for RPL554 to stimulate numerous rare class III and IV CFTR mutations is an important advancement for CF patients as it highlights RPL554 as a novel therapeutic. Current FDA-approved therapies are limited in their ability to address this need for patients," said Dr. Turner.

"We are encouraged by the positive data being accrued from pre-clinical and clinical studies with RPL554 in both CF and COPD," said Jan-Anders Karlsson, PhD, CEO of Verona Pharma. "RPL554 has been well-tolerated and demonstrated bronchodilator and anti-inflammatory activity in our extensive COPD clinical trial program and we are encouraged that this dual effect also shows promise in CF. There remains a high unmet need among CF patients to address inflammation which is known to cause disease progression and can lead to worsening of symptoms as well as pulmonary exacerbations."

Verona Pharma has demonstrated in previous Phase 2 trials in patients with COPD that RPL554 significantly improves lung function, including improved peak lung function, reduced lung hyperinflation, and faster onset-of-action, when added to some of the most commonly used COPD treatments, including tiotropium, ipratropium, and albuterol. Verona Pharma is currently conducting a Phase 2 clinical trial to evaluate RPL554 as an add-on treatment to dual LAMA/LABA therapy and triple LAMA/LABA/ICS therapy, as part of a comprehensive clinical program to fully demonstrate the clinical utility of RPL554 in improving the standard of care for COPD. These data will also support the planning of the RPL554 Phase 3 COPD program.

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 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 treatment potential for RPL554, the results of the Phase 2a trial of RPL554 supporting the further development of RPL554 in CF, 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 CF, and the value of the data and insights that may be gathered from the Phase 2 clinical trial, including for the purpose of designing pivotal Phase 3 trials.

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 and the completion of our Phase 2 trial; we may not be successful in developing RPL554 for multiple indications; our ability to obtain regulatory approvals necessary to conduct later stage trials and to 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.

For further information, please contact:

Verona Pharma plcTel: +44 (0)20 3283 4200

Jan-Anders Karlsson, Chief Executive Officer

Stifel Nicolaus Europe Limited (Nominated Adviser and UK Broker)Tel: +44 (0) 20 7710 7600

Stewart Wallace / Jonathan Senior / Ben Maddison

FTI Consulting (UK Media and Investor enquiries)Tel: +44 (0)20 3727 1000

Simon Conway / Natalie Garland-Collins

ICR, Inc. (US Media and Investor enquiries)

James HeinsTel: +1 203-682-8251

Stephanie CarringtonTel. +1 646-277-1282

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