Rodatristat Ethyl – a Peripherally Acting TPH Inhibitor
Altavant’s lead candidate is rodatristat ethyl*, a prodrug of a tryptophan hydroxylase (TPH) inhibitor designed to block peripheral serotonin production. By lowering circulating levels of the hormone, rodatristat may represent a disease-modifying treatment in diseases characterized by excessive production of serotonin. These diseases include pulmonary arterial hypertension and idiopathic pulmonary fibrosis.
Rodatristat, delivered as a prodrug (rodatristat ethyl), is an orally bioavailable direct and reversible TPH inhibitor. Its molecular structure was designed to prevent it from crossing the blood-brain barrier, thereby restricting its effect to peripheral serotonin. Indeed, in nonclinical studies rodatristat did not lower CNS levels of serotonin. By lowering only circulating serotonin, rodatristat may treat diseases characterized by excessive production of peripheral serotonin without the liability of impacting the CNS.
Altavant’s initial focus is pulmonary arterial hypertension (PAH), a rare disease characterized by a thickening and constriction of the smooth muscle layer of pulmonary arteries that is in part driven by excess serotonin signaling. Altavant believes that this novel treatment mechanism has potential to reverse pulmonary remodeling when used in combination with existing PAH treatments.
Preclinical Results Presented at PVRI 2019
Data from preclinical and Phase 1 clinical studies were presented at the Pulmonary Vascular Research Institute (PVRI) 13th Annual World Congress on Pulmonary Vascular Disease. The preclinical results provided evidence that treatment with rodatristat reduces the extent of vascular remodeling in animal models of PAH. In Phase 1 studies in healthy adults, rodatristat was generally well tolerated and lowered serotonin production to levels comparable to those associated with efficacy in preclinical studies.
The U.S. FDA and EU EMA granted rodatristat ethyl orphan status under the Orphan Drug Designation program.