Verona Pharma plc, a biopharmaceutical company, focuses on developing and commercializing innovative therapeutics for the treatment of respiratory diseases with significant unmet medical needs.
On June 26, 2024, the U.S. Food and Drug Administration (‘FDA’) approved Ohtuvayre (ensifentrine) for the maintenance treatment of chronic obstructive pulmonary disease (‘COPD’) in adult patients, and the company launched Ohtuvayre in the U.S. through an exclusive network of accredited specialty pharmaci...
Verona Pharma plc, a biopharmaceutical company, focuses on developing and commercializing innovative therapeutics for the treatment of respiratory diseases with significant unmet medical needs.
On June 26, 2024, the U.S. Food and Drug Administration (‘FDA’) approved Ohtuvayre (ensifentrine) for the maintenance treatment of chronic obstructive pulmonary disease (‘COPD’) in adult patients, and the company launched Ohtuvayre in the U.S. through an exclusive network of accredited specialty pharmacies in August 2024. Ohtuvayre is the company’s first commercial product and the first inhaled therapy with a novel mechanism of action available for the maintenance treatment of COPD in more than 20 years.
Ohtuvayre is a first-in-class selective dual inhibitor of the enzymes phosphodiesterase 3 and 4 (‘PDE3’ and ‘PDE4’), that combines bronchodilator and non-steroidal anti-inflammatory effects in one molecule. Ohtuvayre is delivered directly to the lungs through a standard jet nebulizer without the need for high inspiratory flow rates or complex hand-breath coordination.
The company is commercializing Ohtuvayre for the maintenance treatment of COPD in the U.S. Outside the U.S., it intends to license Ohtuvayre to companies with expertise and experience in developing and commercializing products in those regions. To that end, the company has entered into a strategic collaboration with Nuance Pharma Limited, a Shanghai-based specialty pharmaceutical company (‘Nuance Pharma’), to develop and commercialize ensifentrine, including Ohtuvayre, in Greater China. In February 2025, Nuance announced that Ohtuvayre was approved in Macau, the first approval outside of the U.S., for the maintenance treatment of COPD in adult patients. In addition, in September 2024, Nuance completed enrollment in its own pivotal Phase 3 trial evaluating ensifentrine for the maintenance treatment of COPD in China, and results are expected in mid-2025.
The approval of Ohtuvayre in the U.S. was based on extensive data, including the Phase 3 ENHANCE (‘Ensifentrine as a Novel inHAled Nebulized COPD thErapy’) trials, the results of which have been published in the American Journal of Respiratory and Critical Care Medicine (‘AJRCCM’). Ohtuvayre met the primary endpoint in both the ENHANCE-1 and ENHANCE-2 trials, demonstrating statistically significant and clinically meaningful improvements in measures of lung function. In addition, other endpoint data demonstrated that Ohtuvayre substantially reduced the rate and risk of COPD exacerbations in ENHANCE-1 and ENHANCE-2. Ohtuvayre was well tolerated in both trials.
During 2024, the company presented additional analyses of data from the ENHANCE trials at international scientific conferences, and the data were published in peer-reviewed publications:
In May 2024, the company presented eight posters, including two mini oral symposia, highlighting additional pooled analyses of the ENHANCE studies at the American Thoracic Society International Conference (‘ATS’) 2024. A pooled analysis demonstrating reductions in the rate and risk of exacerbations with Ohtuvayre was presented as part of the ‘Late Breaking Mini Symposium’ focusing on new breakthroughs. In addition, the company hosted an exhibition booth exploring the role of PDE in inflammation and lung function impairment in COPD, as well as three innovation hub presentations led by clinical experts.
In September 2024, the company gave an oral presentation and presented three posters on additional analyses from the ENHANCE studies at the European Respiratory Society International Congress 2024. The analyses summarized the efficacy and safety of Ohtuvayre in subgroups of patients, and a pooled analysis of patient-reported outcomes demonstrated its effect on reducing cough and sputum. The abstracts were published in the publication, European Respiratory Journal; and
In October 2024, the company gave four oral presentations and presented two posters on analyses from the ENHANCE studies at CHEST Annual Meeting 2024 (‘CHEST’). These included subgroup data supporting improvements in lung function, symptoms, and quality of life, as well as reductions in the rate of exacerbations, regardless of COPD severity (moderate or severe), smoking status (current or former), and chronic bronchitis (with or without). An analysis of Ohtuvayre’s impact on reducing exacerbation rates and COPD-related healthcare resource utilization was also presented. The analyses were published in the CHEST Annual Meeting online supplement.
Pipeline
In Phase 2 clinical trials, ensifentrine has demonstrated positive results in patients with COPD, asthma, and cystic fibrosis (‘CF’). Two additional formulations of ensifentrine have been evaluated in Phase 2 trials for the treatment of COPD: dry powder inhaler (‘DPI’), and pressurized metered-dose inhaler (‘pMDI’).
In addition, in the third quarter of 2024, the company initiated two Phase 2 clinical trials: a dose-ranging trial with glycopyrrolate, a Long-Acting Muscarinic Antagonist (‘LAMA’), supporting a fixed-dose combination program with ensifentrine for the maintenance treatment of COPD via delivery in a nebulizer, and a trial assessing the efficacy and safety of nebulized ensifentrine in patients with non-cystic fibrosis bronchiectasis (‘bronchiectasis’).
Ensifentrine
Ensifentrine is a first-in-class, inhaled, small molecule and selective, dual PDE3 and PDE4 inhibitor. This dual inhibition enables it to act as a bronchodilator and a non-steroidal anti-inflammatory agent in a single compound. Importantly, ensifentrine’s therapeutic profile differentiates it from existing classes of bronchodilator and anti-inflammatory treatments. The company is not aware of any other single compound in clinical development in the U.S. or Europe, or approved by the FDA or the European Commission for the treatment of respiratory diseases that acts both as a bronchodilator and anti-inflammatory agent. Ensifentrine is the first novel inhaled mechanism approved for the maintenance treatment of COPD in over 20 years, and the only bronchodilator option that can be added to existing classes of inhaled therapies, including LAMA, LABA, and ICS.
Phase 3 ENHANCE program
The U.S. approval of Ohtuvayre was based on extensive data, including the Phase 3 ENHANCE trials, the results of which were published in the American Journal of Respiratory and Critical Care Medicine.
The company reported positive top-line results from ENHANCE-2 and ENHANCE-1 in August and December 2022, respectively. Ohtuvayre successfully met the primary endpoints in both trials, demonstrating statistically significant and clinically meaningful improvements in measures of lung function in moderate to severe COPD patients. Improvements in symptoms and quality of life measures were shown in both trials, which reached statistical significance in ENHANCE-1. Other endpoint data showed Ohtuvayre substantially reduced the rate and risk of moderate to severe COPD exacerbations, and was well tolerated in both trials.
The ENHANCE trials were designed to evaluate Ohtuvayre as monotherapy and added onto a single bronchodilator. Each trial enrolled approximately 800 subjects, for a total of approximately 1,600 subjects, at sites primarily in the U.S. and Europe. The two trials provided replicate evidence of efficacy and safety data over 24 weeks, and ENHANCE-1 also evaluated longer-term safety in approximately 400 subjects over 48 weeks.
Subject demographics and disease characteristics were well balanced between treatment groups in both trials.
In ENHANCE-1, approximately 69% of subjects received background COPD therapy, either a LAMA or a LABA. Additionally, approximately 20% of all subjects received ICS with concomitant LAMA or LABA.
In ENHANCE-2, approximately 55% of subjects received background COPD therapy, either a LAMA or a LABA. Additionally, approximately 15% of all subjects received ICS with concomitant LAMA or LABA.
The totality of data from clinical trials, in particular the top-line results from the ENHANCE program, including improvements in measures of lung function, symptoms, quality of life measures, and exacerbation reductions, coupled with the consistent safety results, support the company’s belief.
Formulations
The company has developed formulations of ensifentrine for the three most widely used inhalation devices: nebulizer, DPI, and pMDI. The nebulized formulation of ensifentrine is designed for use in a standard jet nebulizer, not a proprietary device.
In February 2021, the company reported positive results from the second, multiple dose part of a Phase 2 trial with pMDI ensifentrine in patients with moderate to severe COPD. Ensifentrine delivered by pMDI met all of the primary and secondary lung function endpoints. The improvement in lung function was dose-ordered and statistically significant at peak and over the 12-hour dosing interval compared with placebo, and supports twice-daily dosing of ensifentrine via pMDI for the treatment of COPD. Data from the single dose part of the study were reported in March 2020.
The company has successfully demonstrated proof of concept in Phase 2 COPD trials with all three formulations. In addition, the data from Phase 2 trials were consistent across the three formulations. All three dosage forms have demonstrated statistically significant and clinically meaningful improvements in lung function and duration of action, supporting twice-daily dosing and a safety profile similar to placebo.
Ensifentrine / Long-Acting Muscarinic Antagonist fixed-dose combination
Fixed-dose combination therapies, such as LABA / LAMA, LABA / ICS, and LABA / LAMA / ICS, are commonly used in the treatment of COPD, and, based on the company’s market research, an unmet need exists for a nebulized fixed-dose combination therapy.
The company is developing a fixed-dose combination formulation with ensifentrine and glycopyrrolate, a LAMA, for the maintenance treatment of patients with COPD via delivery in a nebulizer. It has filed patent applications in multiple jurisdictions, including the U.S.
In November 2024, the company completed enrollment in a Phase 2 dose-ranging trial with glycopyrrolate, a LAMA, supporting a fixed-dose combination program for the maintenance treatment of COPD via a nebulizer. The glycopyrrolate dose-ranging trial has successfully completed, and the company plans to initiate a Phase 2b trial with a fixed-dose combination of ensifentrine and glycopyrrolate in the second half of 2025.
In the third quarter of 2024, the company began enrollment in a Phase 2 clinical trial to assess the efficacy and safety of nebulized ensifentrine in patients with bronchiectasis.
In a Phase 2a clinical trial, a single dose of nebulized ensifentrine demonstrated an improvement in lung function in patients with CF. In addition, in preclinical studies, ensifentrine activated the cystic fibrosis transmembrane conductance regulator (‘CFTR’), which is beneficial in reducing mucous viscosity and improving mucociliary clearance.
Intellectual Property
As of December 31, 2024, the company’s patent portfolio included twelve issued U.S. patents, sixteen pending U.S. patent applications (including three U.S. provisional patent applications), ninety-seven issued foreign patents, and eighty-three pending foreign applications (including eight international PCT applications). These patents and patent applications include claims directed to certain respirable formulations comprising ensifentrine, a crystalline form of ensifentrine, combinations of ensifentrine with certain respiratory drugs, certain salts, and other solid forms of ensifentrine, and ensifentrine for use in certain treatments of particular respiratory disorders, with expected expiry dates up to 2045.
The company has registered ‘Verona Pharma’ and its associated logo as trademarks in the U.S. and certain other key jurisdictions, including the EU and UK. It has also registered ‘Ohtuvayre’ and ‘Verona Pathway Plus’, including their respective logos, in the EU and UK, and has made applications to register in the U.S. and certain other key jurisdictions.
License agreement with Ligand
In February 2005, Rhinopharma Limited (‘Rhinopharma’) entered into an assignment and license agreement with Ligand UK Development Limited (‘Ligand’), which, since October 2018, has been a wholly owned subsidiary of Ligand Pharmaceuticals, Inc. In 2006, the company acquired Rhinopharma and all its rights and liabilities under the assignment and license agreement. On March 24, 2022, it entered into an agreement with Ligand to amend the assignment and license agreement. The company refers to the assignment and license agreement and the amendment agreement together as the Ligand Agreement. Pursuant to the Ligand Agreement, Ligand has assigned to the company all its rights to certain patents and patent applications relating to ensifentrine and related compounds, or the Ligand Patents.
The Ligand Agreement expires on March 24, 2042, unless terminated earlier by either party in accordance with its terms. Either party may terminate the Ligand Agreement for bankruptcy or insolvency of the other party, or for an uncured material breach of the other party, conditional upon the party seeking to terminate obtaining a final judgment of the English High Court declaring that the other party is in material breach of its obligations under the Ligand Agreement.
Government Regulation
The FDA and comparable regulatory authorities in state and local jurisdictions, and in other countries, impose substantial and burdensome requirements upon companies involved in the clinical development, manufacture, marketing, and distribution of drugs, such as those the company is developing.
In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservation and Recovery Act, and the Toxic Substances Control Act, affect the company’s business.
Research and Development
The company’s research and development costs were $44.6 million for the year ended December 31, 2024.
History
Verona Pharma plc was founded in 2005. The company was incorporated in 2005 under the laws of England and Wales.
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