Verona Pharma Reports Financial Results for Full Year Ended December 31, 2018 and Provides Clinical Development Update
LONDON, Feb. 26, 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 its audited results for the full year ended December 31, 2018 and provides a clinical development update.
OPERATIONAL AND DEVELOPMENT HIGHLIGHTS
Solid clinical progress with ensifentrine (RPL554) nebulizer formulation; demonstrating efficacy and tolerability in chronic obstructive pulmonary disease (COPD).
- Reported positive top-line data from a Phase 2b four-week, 403 patient clinical trial for maintenance treatment of COPD:
- ensifentrine met the primary endpoint at all doses (P<0.001), showing a clinically meaningful and statistically significant bronchodilator effect after 4 weeks of dosing;
- this peak bronchodilator effect was sustained over four weeks (p<0.001);
- ensifentrine demonstrated a clinically meaningful and statistically significant, progressive improvement in daily COPD symptoms, using the recognized patient-reported measure of COPD symptoms (E-RS) and the quality of life score St George's Respiratory Questionnaire (SGRQ-C);
- ensifentrine was well tolerated at all doses with an adverse event profile similar to placebo.
- ensifentrine met the primary endpoint at all doses (P<0.001), showing a clinically meaningful and statistically significant bronchodilator effect after 4 weeks of dosing;
Demonstrated efficacy and tolerability in CF.
- Reported positive top-line data from a Phase 2a clinical trial in CF:
- ensifentrine was well tolerated and demonstrated a statistically significant bronchodilator effect;
- PK profile was consistent with that observed in patients with COPD;
- data provides a solid foundation for further development of ensifentrine for the treatment of CF.
- ensifentrine was well tolerated and demonstrated a statistically significant bronchodilator effect;
Advanced DPI and MDI formulations of ensifentrine, with the potential to reach a substantially larger number of COPD patients.
- Selected dry powder inhaler (“DPI”) and pressured metered dose inhaler (“pMDI”) formulations of ensifentrine.
- First DPI clinical trial in COPD patients initiated in December 2018; initial results expected in the first quarter of 2019.
Scientific presentations and Investor R&D forum well received.
- Presented two posters at the American Thoracic Society 2018 International Conference, and two presentations at the NACF conference 2018.
- Published full results from two ensifentrine Phase 2 clinical studies in COPD in the high-impact, peer reviewed European Respiratory Journal.
- Presented an expanded dataset from its Phase 2b study evaluating ensifentrine as a maintenance treatment for COPD in an oral presentation at the European Respiratory Society International Congress.
- Hosted an "Investor and Analyst R&D Forum" in New York City, featuring a panel of Key Opinion Leaders in the field of COPD, as well as representatives from the COPD Foundation and a COPD patient, providing insights into the unmet medical need and the challenges of treating COPD and the need for a novel mechanism of action such as ensifentrine.
FINANCIAL HIGHLIGHTS
- Cash, cash equivalents and short-term investments at December 31, 2018 amounted to £64.7 million (December 31, 2017: £80.3 million);
- For the year ended December 31, 2018, reported operating loss of £25.6 million (full year 2017: £29.8 million) and reported loss after tax of £19.9 million (full year 2017: loss after tax of £20.5 million), reflecting the preparation and initiation of clinical trials and pre-clinical activities;
- Reported loss per share of 18.9 pence for the year ended December 31, 2018 (full year 2017: loss per share 23.4 pence);
- Net cash used in operating activities for the year ended December 31, 2018 of £18.1 million (full year 2017: £20.7 million).
POST PERIOD
Demonstrated that ensifentrine produces additional bronchodilation in patients already receiving maximum bronchodilator treatment with LAMA/LABA therapy.
- Reported top-line data from its 79 patient, three-day Phase 2a trial to explore whether nebulized ensifentrine, with its unique mechanism of action, could add further bronchodilation in patients already receiving maximum standard-of-care dual bronchodilator therapy with an inhaled LAMA/LABA for COPD maintenance treatment:
- ensifentrine demonstrated additional bronchodilation in patients already receiving maximum bronchodilator treatment with LAMA/LABA therapy;
- although the primary endpoint of improvement in peak forced expiratory volume in one second (FEV1) after morning dose on day three of treatment was not statistically significant when added on top of Stiolto® Respimat® compared to placebo, statistically significant improvements in evening peak FEV1 on the third day of dosing, and significant reductions in lung volume after the evening dose of ensifentrine were observed with both the 1.5 mg and 6 mg dose groups, compared to placebo, when administered on top of Stiolto® Respimat®;
- this improvement in FEV1 with the 1.5 mg dose was maintained throughout the 24-hour period as measured on day 3.
- ensifentrine demonstrated additional bronchodilation in patients already receiving maximum bronchodilator treatment with LAMA/LABA therapy;
Completed enrollment in Part 1 of the Company’s two-part Phase 2 clinical study using the DPI formulation to treat approximately 30 COPD patients.
- The Company expects to report interim efficacy and safety data from Part 1 of this study in the first quarter of 2019. Part 1 of this study comprises of measurement of lung function, safety and pharmacokinetic profiling in COPD patients following a single dose of inhaled ensifentrine over a dose range.
- Part 2 of this study will comprise of a crossover study evaluating a range of ensifentrine doses in this same patient cohort dosed over 1 week. The Company expects to initiate Part 2 of the study in the first quarter of 2019, and to report data in the second half of 2019.
Strengthened the management team through the additions of Kathleen Rickard, MD, as Chief Medical Officer, and Tara Rheault, PhD, MPH, as Vice President of Research and Development Operations and Global Project Management.
For further information, please contact:
Verona Pharma plc | Tel: +44 (0)20 3283 4200 |
Jan-Anders Karlsson, Chief Executive Officer | info@veronapharma.com |
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 | veronapharma@fticonsulting.com |
ICR, Inc. (US Media and Investor enquiries) | |
Darcie Robinson | Tel: +1 203-919-7905 Darcie.Robinson@icrinc.com |
Stephanie Carrington | Tel. +1 646-277-1282 Stephanie.Carrington@icrinc.com |
An electronic copy of the annual report and accounts will be made available today on the Company's website (http://www.veronapharma.com). A copy of the Form 20-F will be filed with the SEC as soon as possible. This press release does not constitute an offer to sell or the solicitation of an offer to buy securities, and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of that jurisdiction.
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, 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. In previous clinical trials, the nebulized formulation of ensifentrine 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. Ensifentrine 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, ensifentrine has shown anti-inflammatory effects in a standard challenge study with COPD-like inflammation in human subjects. Ensifentrine has been well tolerated in these studies, having been administered to more than 800 subjects in 13 clinical trials. Verona Pharma is developing ensifentrine for the treatment of COPD, CF, and 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 that there is an opportunity for additional bronchodilator and symptomatic improvement via the novel mechanism of action of ensifentrine and Verona Pharma’s plans to carry out further long-term clinical studies of ensifentrine as an add-on to both single and dual bronchodilator therapy and the expectation that even more profound anti-inflammatory effects, leading to improvements in lung function, as well as improvements in symptoms will result.
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.
CHAIRMAN AND CHIEF EXECUTIVE OFFICER’S JOINT STATEMENT
OVERVIEW
Significant progress in development and identification of compelling market opportunities
We are initially developing ensifentrine as a nebulized formulation for the maintenance treatment of uncontrolled, symptomatic, moderate to severe COPD patients. Our market research shows that nebulized delivery is the preferred route of administration for more severe COPD patients, especially in the US, thus providing an attractive commercial opportunity. The regulatory pathway for the development of nebulized drug products is well-established.
COPD is a progressive respiratory disease with no cure. Our market research demonstrates that, in the US alone, approximately two million patients remain uncontrolled and symptomatic despite taking currently available medications. Few therapeutic alternatives are available for these patients.
Ensifentrine is potentially a treatment alternative for these symptomatic COPD patients. The past year has seen significant clinical progress with the successful completion of the first four-week phase 2b study with nebulized ensifentrine in 403 patients with COPD. Ensifentrine produced a clinically meaningful bronchodilator effect and a progressive improvement in symptoms suggesting an anti-inflammatory effect in these COPD patients. A further Phase 2 study initiated last year, and reported in January this year, demonstrated that ensifentrine provides further bronchodilation when added on top of what was formerly presumed to be maximum bronchodilator treatment with dual or triple COPD standard-of-care treatment.
In our clinical program, which to date has consisted of 13 studies which have enrolled over 800 human subjects, we have demonstrated that ensifentrine is an effective bronchodilator in COPD patients with or without concurrent bronchodilator therapy. In addition, many Key Opinion Leaders in the field of COPD support our view that the progressive improvement in COPD symptoms observed over a four-week treatment period with ensifentrine is due to an anti-inflammatory effect, attesting to its dual activity.
Taken together, these new data support the inclusion of patients on dual and triple therapy into the later stage clinical development program. Thus, we believe that nebulized ensifentrine could potentially be used to treat symptomatic COPD patients despite taking either a single bronchodilator or dual or triple therapy; an attractive market opportunity estimated to be about 2 million patients in the US alone.
The successful development of DPI and MDI formulations of ensifentrine and the initiation late last year of the DPI Phase 2 clinical trial in COPD patients is another important development milestone. In the US, our market research shows that about 5.5 million moderate to severe COPD patients currently use these types of devices. We expect the DPI formulation to produce a bronchodilator effect in COPD, which we believe would open up another attractive market opportunity. We anticipate that we would partner the DPI/MDI formulations later in development in order to realize the potential of this multi-billion dollar opportunity.
In addition to COPD, we believe ensifentrine could become an attractive development candidate also in cystic fibrosis and severe asthma.
To support the later stage development of ensifentrine, we have strengthened our team with the appointment of Kathleen Rickard, MD, as Chief Medical Officer, and Tara Rheault, PhD, MPH, as VP Research and Development Operations and Global Project Management, who together have extensive expertise in respiratory drug development, regulatory affairs and commercialization.
Ensifentrine - first-in-class bronchodilator and anti-inflammatory agent
We are a clinical-stage biopharmaceutical company focused on developing and commercializing innovative therapeutics for the treatment of respiratory diseases with significant unmet medical need. Our product candidate, ensifentrine (RPL554), is an investigational, potential first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4, or PDE3 and PDE4, that is designed to act as both a bronchodilator and an anti-inflammatory agent. We are not aware of any other product formulated in a single compound in clinical development or approved by the U.S. Food and Drug Administration, or FDA, or the European Medicines Agency, or EMA, for the treatment of respiratory diseases as both a bronchodilator and anti-inflammatory agent. We believe ensifentrine has the potential to be the first novel class of bronchodilator in over 40 years. A nebulized formulation of ensifentrine is currently in Phase 2 clinical development for the treatment of COPD. Successful Phase 1 and 2 studies have been completed with nebulized ensifentrine in healthy volunteers and in patients with cystic fibrosis, or CF, chronic asthma and allergic rhinitis, in addition to COPD. A Phase 2 study in COPD with ensifentrine formulated in a dry powder inhaler is ongoing, and a Phase 2 study in COPD with ensifentrine formulated in a pressurized metered dose inhaler is planned to commence in 2019. We intend to first develop ensifentrine as a nebulized therapy for the treatment of COPD.
For the past 40 years, the treatment of COPD has been dominated by three classes of inhaled therapies approved for use by the FDA or EMA: antimuscarinic agents and beta2-agonists, both available as either short-acting or long-acting bronchodilators, and inhaled corticosteroids, or ICS, known for their anti-inflammatory effects. However, despite existing treatment with one or multiple combinations of these therapies, and owing to the progressive and incurable nature of COPD, many COPD patients on maximum inhaled therapy still experience significant lung function impairment and symptoms for which limited further approved treatment options are available. One such treatment is an oral formulation of a PDE4 inhibitor with anti-inflammatory properties, although frequency of adverse events has limited its use in COPD patients.
We have completed 13 Phase 1 and Phase 2 clinical trials with ensifentrine which have enrolled over 800 subjects with COPD, asthma, cystic fibrosis, or allergic rhinitis or healthy volunteers. In our clinical trials, treatment with ensifentrine has been repeatedly observed to result in statistically significant improvements in lung function as compared to placebo, whether dosed alone or in combination with commonly used short- and long-acting classes of bronchodilators, with or without ICS. Statistically significant means that there is a low statistical probability, typically less than 5%, that the observed results occurred by chance alone. In our Phase 2b clinical trial of nebulized ensifentrine as a maintenance treatment for COPD, patients with moderate-to-severe COPD treated with ensifentrine showed clinically meaningful and statistically significant improvements in daily reported COPD symptom scores. In addition, our clinical trials have also shown clinically meaningful and statistically significant additional improvements in certain measures of lung function following combined treatment with ensifentrine as add-on to other approved bronchodilators; COPD patients experienced a marked reduction in residual lung volume, which is believed to be related to one of the most debilitating symptoms, breathlessness. The rapid onset of action observed when adding ensifentrine on top of tiotropium, a commonly used LAMA, was also notable, and may be particularly helpful to those patients suffering from morning breathlessness. We believe that the clinical effects observed with ensifentrine are driven by its bronchodilator, anti-inflammatory and mucociliary clearance mechanisms.
High unmet medical need in symptomatic COPD patients despite treatment with current standard-of-care
We believe there is an urgent and unmet medical need for new and more effective treatments for COPD to reduce the number and burden of symptoms, reduce acute periods of worsening symptoms, or exacerbations, and establish a consistent and durable response to treatment. In addition, in CF, a fatal inherited disease, we believe the bronchodilatory and anti-inflammatory effects of ensifentrine may be beneficial. We believe ensifentrine, if approved, has the potential to become an important and novel treatment and standard of care for COPD and CF patients. We may also explore, alone or with a collaborator, the development of ensifentrine to treat asthma and other respiratory diseases.
According to the World Health Organization (WHO), over one billion people suffer from chronic respiratory diseases. Among the most common of these afflictions is COPD, which is a progressive respiratory disease for which there is no cure. COPD damages the airways and the lungs and leads to shortness of breath, impacting a person's ability to perform daily activities. Chronic inflammation plays a central role in the pathology of the disease, and is particularly prominent in the airways of COPD patients. COPD includes chronic bronchitis, which refers to the inflammation of the lung and airways that results in coughing and sputum production, and emphysema, which refers to a destruction of distal lung tissue, or air sacs. In some cases, patients with COPD experience exacerbations, which are estimated to cause approximately 1.5 million emergency department visits, 687,000 hospitalizations and 129,000 deaths per year in the United States alone. According to the WHO, COPD is expected to become the third leading cause of death globally by 2030, with 210 million people worldwide suffering from the disease. It is estimated that there are 24 million people with COPD in the United States, only half of whom have been diagnosed. Of those diagnosed with COPD in the United States, more than 2 million suffer from severe or very severe forms of the disease. Total annual medical costs relating to COPD in the United States were estimated to be $32 billion in 2010 and are projected to rise to $49 billion in 2020. Whereas the number of patients diagnosed with COPD in the US continues to increase annually, the growth in numbers in more developing countries, like China, is significantly higher. The prevalence of COPD in China is expected to be about 8% of patients over 40 years of age and is expected to increase in coming years. Global sales of drugs currently indicated for COPD in major markets were approximately $15 billion in 2015 and are expected to grow to $20 billion by 2025.
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 phlegm, or mucus, from the lung. This condition often results in frequent exacerbations and hospitalizations. There is no cure for CF and although current therapies are leading to longer lifespans the median age of death for CF patients is still only around 40 years. CF is considered a rare, or orphan, disease by both the FDA and the EMA. 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. The FDA and the EMA provide incentives for sponsors to develop products for orphan diseases, and we plan to seek orphan drug designation for ensifentrine from both regulators in treating CF. 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. In the 12-month period ended June 30, 2016, global sales of drugs currently indicated for CF totaled $4.1 billion. The global market for CF drugs is expected to increase to $7.0 billion by 2020.
Severe asthma
Asthma is widely seen as a result of chronic inflammation in the lungs. In the United States 18 million people are diagnosed with asthma and the 2015 prescription medicine market sales totaled $13 billion. Established treatments include those adopted from the treatment of COPD (for example, bronchodilators and ICS), anti-IgE agents and leukotriene inhibitors. Approximately 1 million patients in the United States are refractory asthmatic patients who remain uncontrolled on established therapies. These patients are the target for injectable biologic anti-IL-5 agents. Sales of biologics in the United States for the treatment of asthma are forecast to exceed $1.0 billion by 2025.
DEVELOPMENT OF NEBULIZED ENSIFENTRINE
Clinical development of ensifentrine in COPD
In March 2018, which was earlier than expected, we announced top-line data from a Phase 2b four-week, double-blind, placebo-controlled, parallel group, multi-center European study, in 403 patients with moderate-to-severe COPD evaluating the efficacy, safety, and dose-response of nebulized ensifentrine administered twice-daily as a maintenance treatment for COPD.
The study met its primary endpoint, with ensifentrine producing a clinically and statistically significant improvement in peak forced expiratory volume in one second (FEV1) at four weeks in patients with moderate-to-severe COPD compared to placebo. Furthermore, the peak FEV1 was significantly improved at all time points over the four weeks of dosing. Secondary endpoints measuring 12 hour average FEV1, COPD symptoms and Quality of Life were also met and support the potential clinical benefits of ensifentrine for the treatment of COPD.
Primary endpoint:
- Ensifentrine met the primary endpoint at all doses, showing a statistically significant difference vs. placebo (p<0.001) with absolute changes from baseline >200mL in peak FEV1 after 4 weeks of dosing. No minimum effective dose could be determined.
- This peak bronchodilator effect was observed at the first dose and was sustained over four weeks (p<0.001).
Secondary endpoints include:
- Statistically significant improvements in average FEV1 over 12 hours were observed at all doses after the first administration, and this effect was sustained over four weeks.
- This study did not demonstrate consistent improvements in trough FEV1.
- Recording of daily COPD symptoms, using E-RS (EXACT-PRO), a recognized patient-reported outcome measure for use in clinical studies of COPD, demonstrated a significant improvement in total COPD symptoms (p<0.002), including improvements in breathlessness (p<0.02), chest symptoms (p<0.02), and cough and sputum (p<0.02).
- Strong trend of improvement in St. George’s Respiratory Questionnaire (SGRQ-C) designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD of >2.5 units was observed in all dose groups after four weeks.
- Patients’ Global Impression of Change, a scale reflecting the patient’s belief about the efficacy of treatment, indicates that patients felt better on ensifentrine compared to placebo (p<0.01).
- Ensifentrine was well tolerated at all doses with an adverse event profile similar to placebo.
On January 14, 2019 we announced top-line data from an exploratory Phase 2a double blind, placebo-controlled, three way cross-over trial in 79 subjects with COPD, which included two different doses of ensifentrine, 1.5 mg and 6 mg, or placebo, dosed twice-daily for three days, in addition to a dual bronchodilator therapy comprising tiotropium and olodaterol, a commonly used LAMA/LABA, dosed once daily. This clinical trial evaluated the efficacy and safety of ensifentrine dosed on top of LAMA/LABA and LAMA/LABA/ICS, a high hurdle as patients already on maximum bronchodilator treatment have very few treatment alternatives, which was conducted at sites in the United States and in the United Kingdom. We reported top-line data from this trial earlier than expected, in January 2019. The data from this Phase 2a trial demonstrated significantly improved evening peak lung function when ensifentrine was added to tiotropium and olodaterol in patients with moderate-to-severe COPD, although the data did not achieve statistical significance in respect of an improvement in the morning peak lung function.
- Improvement in average FEV1 (additional bronchodilation) following morning dose on the third day (0 - 4 hours) with 1.5 mg of ensifentrine was statistically significant when added on top of Stiolto® (tiotropium plus olodaterol or LAMA/LABA) compared to placebo (1.5 mg, p=0.039) although the improvement in morning peak FEV1 on the third day of dosing, the primary endpoint, was not statistically significant;
- Ensifentrine, compared to placebo, produced a statistically significant improvement in evening peak FEV1 on the third day of dosing (additional bronchodilation) when administered on top of the standard bronchodilator tiotropium plus olodaterol (Stiolto®) (1.5 mg, p<0.001; 6 mg p=0.002);
- Ensifentrine, compared to placebo, produced a statistically significant improvement in residual volume following the evening dose on the third day of dosing when administered on top of the standard bronchodilator tiotropium plus olodaterol (Stiolto®) (1.5 mg, p<0.002; 6 mg p<0.036).
COPD - successful development of DPI and pMDI formulations
In addition to our nebulized formulation of ensifentrine, we have developed both pressurized metered dose inhaler, or pMDI, and dry powder inhaler, or DPI, formulations of ensifentrine for the maintenance treatment of COPD. Development of pMDI and DPI formulations could enable us to expand the ensifentrine clinical development program to include those patients with moderate to severe COPD for whom nebulizer treatment is less attractive.
Delivery of orally inhaled drugs by pMDI or DPI is a mainstay of maintenance treatment for patients with moderate to severe COPD. We believe that over 90% of patients with diagnosed COPD use inhalers, such as a pMDI or DPI, rather than a nebulizer, to administer treatment. It is estimated that, in the United States, approximately 5.5 million patients with moderate to severe COPD use inhalers for maintenance therapy. Successful development of a pMDI or DPI formulation of ensifentrine for moderate disease would greatly expand the addressable market for the drug and represents a multi-billion dollar potential opportunity.
We have completed enrollment in Part 1 of our 2-part Phase 2 clinical study using the DPI formulation to treat COPD patients, and we now expect interim efficacy and safety data from Part 1 of this study in the first quarter of 2019. Part 1 of this study comprises measurement of lung function, safety and pharmacokinetic profiling in COPD patients following a single dose of inhaled ensifentrine over a dose range. Part 2 of this study will comprise a crossover study evaluating a range of ensifentrine doses in this same patient cohort dosed over one week. We expect to initiate Part 2 of the study in the first quarter of 2019, and to report data in the second half of 2019.
We expect to initiate a Phase 2 clinical study using the pMDI formulation to treat COPD patients during the first half of 2019, with data expected in 2020; the clinical trial design will be similar to the DPI clinical trial.
We may also explore the development of ensifentrine in pMDI and/or DPI formulations for the treatment of asthma and other respiratory diseases.
Ensifentrine is effective in a short proof-of-concept study in patients with Cystic Fibrosis
In March 2018 we also announced top-line data from a Phase 2a clinical trial to study pharmacokinetic and pharmacodynamic profile of nebulized ensifentrine in CF patients:
- Ensifentrine demonstrated a statistically significant bronchodilator effect.
- PK profile was consistent with that observed in patients with COPD.
- Ensifentrine was well tolerated.
With a strong focus on moving towards Phase 3 clinical trials with nebulized ensifentrine for the maintenance treatment of COPD we are prioritizing our resources and funding initially on the maintenance market in the short term, over progressing our planned trials to evaluate nebulized ensifentrine as a treatment for acute exacerbations of COPD in hospitalized patients and as a treatment for CF patients.
CORPORATE
Ensifentrine is protected by granted and pending patents. We believe that medicinal products containing ensifentrine are protected by our IP beyond 2035. We have worldwide commercialization rights for ensifentrine. We raised £70m in gross proceeds from investors from our April 2017 global offering comprising an initial public offering (“IPO”) on the Nasdaq Global Market (“Nasdaq”), and a concurrent European private placement, together with a shareholder private placement. Members of our management team, which we have strengthened and expanded during the year, and our board of directors have extensive experience in large pharmaceutical and biotechnology companies, particularly in respiratory product development from drug discovery through commercialization and have played important roles in the development and commercialization of several approved respiratory treatments, including Symbicort, Daliresp/Daxas, Flutiform, Advair, Breo Ellipta and Anoro Ellipta.
FINANCIALS
The operating loss for the year ended December 31, 2018 was £25.6 million (2017: £29.8 million) and the loss after tax for the year ended December 31, 2018 was £19.9 million (2017: £20.5 million).
Research and Development Costs
Research and development costs were £19.3 million for the year ended December 31, 2018 as compared to £23.7 million for the year ended December 31, 2017, a decrease of £4.4 million. The cost of clinical trials reduced by £5.9 million as there were four active trials in the year ended December 31, 2017, including a four week Phase 2b trial for COPD maintenance treatment, compared to two clinical trials in the year ended December 31, 2018. Pre-clinical costs also reduced by £0.4 million. These reductions were offset by a £2.0 million increase in contract manufacturing and formulation development costs. Personnel related costs increased by £0.1 million in the year ended December 31, 2018, compared to the prior year.
General and Administrative Costs
General and administrative costs were £6.3 million for the year ended December 31, 2018 as compared to £6.0 million for the year ended December 31, 2017, an increase of £0.3 million. The increase was primarily attributable to a £0.3 million increase in the non-cash share-based payment charge, a £0.2 million increase in personnel related costs and a £0.4 million increase in other overhead costs. This was offset by a £0.6 million decrease in commercial research costs and a decrease in professional fees related to the global offering and shareholder private placement, which occurred in 2017.
Finance Income and Expense
Finance income was £2.8 million for the year ended December 31, 2018 and £7.0 million for the year ended December 31, 2017. The decrease was primarily due to an increase in the fair value of the warrant liability in the year ended December 31, 2018 (which is a non-cash item, recorded as a finance expense) compared to a decrease in the liability in the year ended December 31, 2017, which resulted in a non-cash gain (recorded as finance income) of £6.7 million in 2017. There was a foreign exchange gain on cash and short term investments of £1.9 million in the year ended December 31, 2018, and a loss in the prior year (recorded in finance expense). Furthermore, £0.9 million of interest was received in the year ended December 31, 2018 (2017: £0.3 million).
Finance expense was £1.3 million for the year ended December 31, 2018 as compared to £2.5 million for the year ended December 31, 2017. The movement was due to an increase in the fair value of the warrant liability of £1.2 million, recorded in finance expense, compared to a reduction in the value of the liability in 2017 (recorded in finance income), both non-cash items. In addition, there was a foreign exchange loss on cash and short-term investments in 2017 of £2.4 million. In the year ended December 31, 2018, there was a foreign exchange gain (recorded in finance income).
As at December 31, 2018, there was approximately £19.8 million in cash and cash equivalents (2017: £31.4 million) and £44.9 million in short-term investments (2017: £48.8 million).
Taxation
Taxation for the year ended December 31, 2018 amounted to a credit of £4.2 million as compared to a credit of £4.7 million for the year ended December 31, 2017, a decrease in the credit amount of £0.5 million. The credits are obtained at a rate of 14.5% of 230% of our qualifying research and development expenditure, and the decrease in the credit amount was primarily attributable to our reduced expenditure on research and development.
OUTLOOK AND STRATEGY
We intend to become a leading biopharmaceutical company focused on the treatment of respiratory diseases with significant unmet medical needs. The key elements of our strategy to achieve this goal include:
- Rapidly advance the development of nebulized ensifentrine for the maintenance treatment of COPD in moderate and severe patients.
- For the maintenance treatment of COPD patients, we plan to conduct a further four-week dose-range finding Phase 2b clinical trial to evaluate ensifentrine when dosed in addition to LAMA therapy, compared to placebo. We expect to commence this study in the second quarter of 2019, with top-line data expected by the end of 2019. We will discuss the outcome with the FDA prior to the planned initiation of Phase 3 clinical trials in 2020.
- Ensifentrine for nebulized administration is currently presented in a glass vial with a flip, tear-up cap. This format is adequate for clinical trials but patient acceptance in a commercial setting is expected to be improved by a switch to presenting the suspension formulation of ensifentrine in plastic ampules, which is also more cost effective for manufacturing in larger volumes. This development work is ongoing.
- For the treatment of COPD patients who may prefer the more convenient administration of an inhaler device, we are developing ensifentrine in inhaler formulations. We have commenced a clinical trial in COPD patients with a DPI formulation of ensifentrine and in the first half of 2019 we plan to commence a clinical trial in COPD patients with a pMDI formulation of ensifentrine.
- Proceeding more rapidly towards Phase 3 clinical trials with nebulized ensifentrine for the maintenance treatment of COPD may require us to focus our financial and other resources on maintenance treatment of COPD with nebulized and inhaled formulations of ensifentrine in the short term, which may alter our timing to commence further trials using ensifentrine in other indications.
- Advance the development of nebulized ensifentrine for the treatment of acute exacerbations of COPD. We are developing ensifentrine as an add-on therapy to short acting bronchodilators and other commonly used therapies for the treatment of hospitalized patients with acute exacerbations of COPD. The timing for future studies in this indication will remain subject to our decision to move more rapidly towards Phase 3 clinical trials with nebulized ensifentrine for the maintenance treatment of COPD.
- Develop ensifentrine for the treatment of CF. The timing for future studies in this indication will remain subject to our decision to move more rapidly towards Phase 3 clinical trials with nebulized ensifentrine for the maintenance treatment of COPD.
- Pursue development of ensifentrine for other respiratory diseases. We believe that ensifentrine’s properties as an inhaled, dual inhibitor of PDE3 and PDE4 give it broad potential applicability in the treatment of other respiratory diseases, such as severe asthma. We may explore development of ensifentrine to treat other forms of respiratory disease following development of ensifentrine for the treatment of COPD and CF.
- Seek strategic collaborative relationships. We may seek strategic collaborations with market leading biopharmaceutical companies to develop and commercialize ensifentrine. We believe these collaborations could provide significant funding to advance the development of ensifentrine while allowing us to benefit from the development or commercialization expertise of our collaborators.
- Acquire or in-license product candidates for the treatment of respiratory diseases. We plan to leverage our respiratory disease expertise to identify and in-license or acquire additional clinical stage product candidates that we believe have the potential to become novel treatments for respiratory diseases with significant unmet medical needs.
We would like to thank the staff and Board members for all their contributions and shareholders for their continued support during a successful year.
Dr. David Ebsworth Chairman February 26, 2019 | Dr. Jan-Anders Karlsson Chief Executive Officer February 26, 2019 |
VERONA PHARMA PLC
CONSOLIDATED STATEMENT OF COMPREHENSIVE INCOME
FOR THE YEAR ENDED DECEMBER 31, 2018
Notes | Year ended December 31, 2018 | Year ended December 31, 2017 | |||||
£'000s | £'000s | ||||||
Research and development costs | (19,294 | ) | (23,717 | ) | |||
General and administrative costs | (6,297 | ) | (6,039 | ) | |||
Operating loss | 7 | (25,591 | ) | (29,756 | ) | ||
Finance income | 9 | 2,783 | 7,018 | ||||
Finance expense | 9 | (1,325 | ) | (2,465 | ) | ||
Loss before taxation | (24,133 | ) | (25,203 | ) | |||
Taxation — credit | 10 | 4,232 | 4,706 | ||||
Loss for the year | (19,901 | ) | (20,497 | ) | |||
Other comprehensive income / (loss): | |||||||
Items that might be subsequently reclassified to profit or loss | |||||||
Exchange differences on translating foreign operations | 38 | (29 | ) | ||||
Total comprehensive loss attributable to owners of the Company | (19,863 | ) | (20,526 | ) | |||
Loss per ordinary share — basic and diluted (pence) | 5 | (18.9 | ) | (23.4 | ) |
The accompanying notes form an integral part of these consolidated financial statements.
VERONA PHARMA PLC
CONSOLIDATED STATEMENT OF FINANCIAL POSITION
AS OF DECEMBER 31, 2018
Notes | As of December 31, 2018 | As of December 31, 2017 | |||||
£'000s | £'000s | ||||||
ASSETS | |||||||
Non-current assets: | |||||||
Goodwill | 11 | 441 | 441 | ||||
Intangible assets | 12 | 2,134 | 1,969 | ||||
Property, plant and equipment | 13 | 21 | 16 | ||||
Total non-current assets | 2,596 | 2,426 | |||||
Current assets: | |||||||
Prepayments and other receivables | 15 | 2,463 | 1,810 | ||||
Current tax receivable | 4,499 | 5,006 | |||||
Short term investments | 44,919 | 48,819 | |||||
Cash and cash equivalents | 19,784 | 31,443 | |||||
Total current assets | 71,665 | 87,078 | |||||
Total assets | 74,261 | 89,504 | |||||
EQUITY AND LIABILITIES | |||||||
Capital and reserves attributable to equity holders: | |||||||
Share capital | 16 | 5,266 | 5,251 | ||||
Share premium | 118,862 | 118,862 | |||||
Share-based payment reserve | 7,923 | 5,022 | |||||
Accumulated loss | (69,117 | ) | (49,254 | ) | |||
Total equity |
By: Nasdaq / GlobeNewswire
- 26 Feb 2019
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