Cardurion logo - click to return to the homepage


PDE9 Inhibition: Potential to Address Unmet Medical Needs in People with Heart Failure

We believe PDE9 inhibition presents an opportunity to make a meaningful impact in the lives of heart failure patients. With robust scientific rationale behind our work, we are confident we’re on the right path.
Decorative image

The Problem:
Heart Failure Remains a Major Unmet Need
and Is a Leading Cause of Mortality

Heart failure is a serious condition in which the heart cannot pump blood sufficiently to meet the body’s needs. Approximately 6.5 million people in the United States have been diagnosed with heart failure and that number is growing. There are two major types of heart failure:

Heart failure with reduced ejection fraction (HFrEF) occurs when the heart becomes enlarged, with decreased heart muscle function. As a consequence, there is a decrease in the amount of blood that is ejected from the heart with each heartbeat (reduced ejection fraction), causing insufficient flow of blood to the tissues of the body.

Heart failure with preserved ejection fraction (HFpEF) occurs when the heart muscle becomes thickened and stiff. In this form of heart failure, though the ejection fraction remains normal (is preserved), the pressures in the heart are elevated, causing congestion in the lungs and the symptoms of heart failure.

Symptoms of heart failure include fatigue, shortness of breath, and swelling in the feet, ankles, and elsewhere. People with heart failure often require hospitalization and have a significantly increased risk of premature death. While certain existing therapies have been shown to reduce morbidity and mortality in both types of heart failure, a substantial unmet medical need remains.



1 in 5


25% will be readmitted within 30 days

Our Solution:
A Foundational New Treatment for Both Types of Heart Failure, with the Potential for Improved Efficacy When Added to Standard of Care

Decorative image

When the heart is under stress, it activates the beneficial natriuretic peptide signaling pathway, which relaxes heart muscles, reduces hypertrophy (thickness) and reverses excess build-up of fibrous tissue (fibrosis). The beneficial effects of the natriuretic peptide signaling pathway in the heart muscle cell are mediated by cyclic guanosine monophosphate (cGMP), the critical second messenger in this pathway. PDE9 is an enzyme that selectively degrades cGMP, and it is now understood that PDE9 is elevated in all forms of heart failure, limiting the beneficial effects of the natriuretic peptide signaling pathway.

By inhibiting PDE9, our goal is to enhance the natriuretic peptide signaling within heart muscle cells by preserving the cGMP generated by activation of the natriuretic peptide receptor. We have validated this concept extensively in preclinical models, and Cardurion is the first company to test a PDE9 inhibitor in heart failure patients, where we have observed encouraging evidence of clinical activity that supports our preclinical studies. We recently concluded a Phase 2a clinical trial of our PDE9 inhibitor in HFrEF patients who are already treated with guideline-directed medical therapies. We are launching two Phase 2b trials in 500 patients with both forms of heart failure, HFrEF and HFpEF.

The figure below illustrates how the natriuretic peptide signaling pathway impacts activity within a heart cell and how PDE9 inhibition has the potential to provide transformational benefit to patients suffering from heart failure.

This site uses cookies and third-party scripts to provide certain services. View Privacy Policy

Skip to content