Our Challenge

Cardiopulmonary disease is the medical term used to describe a range of serious disorders that affect the heart (“cardio-”) and lungs (“-pulmonary”).

Cardiovascular and respiratory diseases are the leading causes of premature death worldwide. Approximately 1 in 4 of us will die from heart disease and 1 in 5 from lung disease.

 

Half of all deaths from heart disease are sudden and unexpected.

OUR INITIAL FOCUS

PULMONARY ARTERIAL HYPERTENSION

Pulmonary arterial hypertension (PAH) is a rare yet devastating cardiopulmonary disease caused by increased pressure within the blood vessels of the lungs.

 

PAH is just one of a member of a group of related cardiopulmonary diseases, which also includes conditions linked to left heart failure and other types of lung diseases.

Overview of PAH

Sorting Medicine

Treating PAH

PAH cannot be cured without lung transplantation, but treatment can reduce the symptoms and help to slow down the disease. Untreated, PAH has a mean survival of just under 3 years. Recent advances in diagnosis, management and treatment options have extended mean survival to about 4 years, with 1-, 3- and 5-year survival rates of 85%, 67% and 58%, respectively. PAH usually gets worse over time. Left untreated, it causes heart failure, which can be terminal, so it's critical that treatment is started as soon as possible.

The current treatments for PAH fall into four drug classes and mainly treat the excessive pulmonary vasoconstriction or reduced vasodilation to restore or improve basic lung (pulmonary) function. These four drug classes include:

  • Endothelin receptor (ET) antagonists (ERAs), that inhibit excessive ET-induced vasoconstriction by mainly targeting the ETA receptor.​

  • Phosphodiesterase (PDE) type 5 inhibitors that inhibit breakdown of cGMP and cAMP, prolonging the actions of nitric oxide (NO) and the prostanoid Prostacyclin, respectively.​

  • Stimulators of soluble guanylyl cyclase (sGC), that aim to enhance NO/cGMP-induced vasodilation.​

  • Prostacyclin analogues and receptor agonists, that restore Prostacyclin/cAMP-induced vasodilation.

However, these current therapies mainly treat the reduced vasodilation to lower pulmonary vascular resistance and improve exercise capacity, but do little to treat the other major clinical features of the disease or to reduce disease progression. Thus, patient outcomes remain poor. Despite several PAH therapies being made available over the past 25 years or longer, patients often comment on the downsides of current therapies, including fears of site infections and how living with an intravenous line impacts daily activities. For females with PAH, the emotional burden of monthly pregnancy testing and counselling required by some of their medications is difficult to bear. Access to therapies through specialty pharmacies only, an often high frequency of dosing and cumbersome route of administration are also noted to be major factors in poor compliance with existing treatment regimes.

 

There is an urgent unmet medical need for new targets and therapeutic drugs that offer greater tolerability/compliance and overall clnical outcome (efficacy).

Learn More About PAH