FOCUSED ON THE DEVELOPMENT OF TRANSFORMATIVE THERAPIES FOR THE TREATMENT OF :
Worsening heart failure
Hyponatremic acute heart failure
Worsening heart failure
Worsening heart failure
Worsening heart failure
Biology
CRF2 (Corticotropin-releasing hormone receptor 2) is a plasma membrane receptor widely expressed in the cardiovascular, renal and metabolic systems.
In proof of concept studies in heart failure patients and in preclinical heart failure models, CRF2 agonists :
- Improve cardiac function and reduce pulmonary congestion
- Promote diuresis/natriuresis on top of standard of care without triggering a neurohumoral response
In right heart failure patients or models, CRF2 agonists:
- Reduce the left ventricular filling pressure
- Improve the right cardiac function and pulmonary arterial resistance
- Improve the cardiac remodeling
In sarcopenia patients or sarcopenia models, CRF2 agonists :
- Increase the skeletal muscle mass
- Improve skeletal muscle function
In obese patients or preclinical models, CRF2 agonists :
- reduce body weight and % of fat mass
- preserve the lean mass
CRF2
Strategy
Endogenous ligands for CRF2 (urocortin 2 or stresscopin) have a very short half-life which makes them unsuitable for sub-chronic administration in an outpatient setting. Our strategy is to develop two potent, long acting and selective CRF2 agonists, one suitable for once daily subcutaneous administration for the treatment of worsening heart failure, and a second for a once monthly administration for the treatment of right heart failure and potentially other indications such as obesity or sarcopenia.
