There is strong evidence from both pre-clinical models and human studies implicating elevated levels of serotonin or increased serotonin activity in the periphery in a variety of diseases such as pulmonary arterial hypertension (PAH), certain types of cancer, GI disorders, fibrosis and inflammation.
In pulmonary arterial hypertension, excess serotonin in the periphery stimulates the thickening and constriction of the pulmonary blood vessels, which leads to increased arterial blood pressure in the lungs and an increased workload for the heart.
We believe that direct inhibition of tryptophan hydroxylase (TPH), the rate-limiting enzyme in the production of serotonin, with an orally bioavailable, peripherally restricted, direct enzyme inhibitor, represents a potential novel treatment that has the potential to reverse pulmonary remodeling when used in combination with existing PAH treatments.
A phase 1 clinical study in healthy adults is completing in the near future and is designed to evaluate the safety and tolerability of rodatristat ethyl*. Phase 2 clinical trials in people living with PAH are expected to launch in 2019.