Ensifentrine's unique mechanism of action has the potential to have a major impact on the treatment of respiratory diseases.

Key activities

Ensifentrine combines bronchodilator and anti-inflammatory properties in one compound and has the potential to be an effective treatment for COPD and other respiratory diseases, including asthma and cystic fibrosis.

Ensifentrine has been well tolerated in clinical trials involving over 1300 people. It is designed to maximize its effectiveness and reduce adverse events through:

  • high selectivity for PDE3 and PDE4 over other enzymes and receptors to minimize off-target effects;

  • direct delivery to the lungs by inhalation to maximize pulmonary exposure to ensifentrine while minimizing systemic distribution and potential adverse events.

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Unique mechanism of action

Unique mechanism of action

Meet Ensifentrine

Ensifentrine is a first-in-class, inhaled, dual inhibitor of the phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4) enzymes. This dual inhibition enables it to combine bronchodilator and anti-inflammatory properties in one compound, differentiating it from existing drug classes used to treat COPD, including corticosteroids, beta2-agonists and anti-muscarinics.

Ensifentrine also activates the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), which is beneficial in reducing mucous viscosity and improving mucociliary clearance. This potentially makes it an attractive therapy for the treatment of cystic fibrosis.

Product Pipeline

Ensifentrine has the potential to substantially improve both lung function and quality of life of respiratory patients who are not satisfactorily treated with available drugs. We are evaluating nebulized ensifentrine in a Phase 3 clinical program ENHANCE (Ensifentrine as a Novel inHAled Nebulized COPD thErapy) for COPD maintenance treatment. Additionally, two other formulations of ensifentrine are in Phase 2 development for the treatment of COPD: dry powder inhaler (DPI) and pressurized metered-dose inhaler (pMDI).

In Phase 2 studies in patients with moderate-to-severe COPD, our lead formulation, nebulized ensifentrine, has demonstrated significant and clinically meaningful improvements in both lung function and COPD symptoms, including breathlessness. These benefits have been observed with or without background therapy. In addition, nebulized ensifentrine has further improved lung function and reduced residual lung volumes (air trapping) in COPD patients taking standard of care, short- and long-acting bronchodilator therapy, including maximum bronchodilator treatment with dual/triple therapy (LABA/LAMA +/- ICS).

We reported positive results from a Phase 2 study of the DPI formulation of ensifentrine in August 2019. Positive data with a single dose of pMDI formulation of ensifentrine in a Phase 2 trial were reported in March 2020 and with multiple doses in February 2021. Ensifentrine also has potential applications in cystic fibrosis, asthma and other respiratory diseases.


This range of Verona Pharma-supported publications provide further pharmacologic background to the research that we are engaged in.

A dose-ranging study of the novel inhaled dual PDE 3 and 4 inhibitor ensifentrine in patients with COPD receiving maintenance tiotropium therapy. Study 205.

Gary T Ferguson, Edward M Kerwin, Tara Rheault, Thomas Bengtsson, Kathleen Rickard

International Journal of Chronic Obstructive Pulmonary Disease, April 22, 2021

The phosphodiesterase inhibitor ensifentrine reduces production of pro-inflammatory mediators in well-differentiated bronchial epithelial cells by inhibiting PDE4

Mark Turner, Nurlan Dauletbaev, Larry Lands and John W. Hanrahan

Journal of Pharmacology and Experimental Therapeutics, 4 October 2020

Symptom improvement following treatment with the inhaled dual phosphodiesterase 3 and 4 inhibitor ensifentrine in patients with moderate to severe COPD – a detailed analysis

Henrik Watz, Kathleen Rickard, Tara Rheault, Thomas Bengtsson, Dave Singh

International Journal of Chronic Obstructive Pulmonary Disease, 16 September 2020

A dose-ranging study of the inhaled dual phosphodiesterase 3 and 4 inhibitor ensifentrine in COPD. Study 203.

Dave Singh, Fernando J. Martinez, Henrik Watz, Thomas Bengtsson, Brian T. Maurer

Respiratory Research, 10 February 2020

Clinical milestones of a candidate COPD treatment

Tara Rheault and Margot Macdonald-Berko

MedNous, July/August 2019

Efficacy and safety of a first-in-class inhaled PDE3/4 inhibitor (ensifentrine) vs salbutamol in asthma

Leif Bjermer, Katharine Abbott-Banner, Kenneth Newman

Pulmonary Pharmacology & Therapeutics, 14 June 2019, 101814

The short-term bronchodilator effects of the dual PDE3 and PDE4 inhibitor RPL554 in COPD

David Singh, Katharine Abbot-Banner, Thomas Bergtsson, Kenneth Newman

Eur. Respir. J. 2018

Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials

Lui G Franciosi, PhD, Prof. Zuzana Diamant, MD, Katharine H Banner, PhD, Rob Zuiker, MD, Nicoletta Morelli, MD, Ingrid M C Kamerling, PhD, Marieke L de Kam, MSc, Prof. Jacobus Burggraaf, MD, Prof. Adam F Cohen, MD, Prof. Mario Cazzola, et al.

The Lancet Respiratory Medicine, October 25 2013, http://dx.doi.org/10.1016/S2213- 2600(13)70187-5

Dual PDE3/4 and PDE4 Inhibitors: Novel Treatments For COPD and Other Inflammatory Airway Diseases

Katharine H. Abbott-Banner and Clive P. Page

Basic & Clinical Pharmacology & Toxicology Doi: 10.1111/bcpt.12209

A combined Phase I/IIa study of the safety, bronchodilator and bronchoprotective effects of nebulized RPL554, a dual PDE3/4 inhibitor, in healthy subjects and asthmatics

Franciosi L, Diamant Z, Morelli N, de Kam M, Cohen A, Walker M, Page CP.

Clin Transl Allergy. 2013; 3 (Suppl 1): O13


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