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.

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Rodatristat Ethyl Mechanism of Action

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

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Healthy pulmonary artery in rat
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Pulmonary artery in rat with PAH
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Pulmonary artery in rat treated with rodatristat ethyl

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.

For more information, see also:

  • Publications related to rodatristat ethyl here
  • Information on rodatristat’s mechanism of action here

*Name applied for; application pending. For ease of reading, this website sometimes uses the name “rodatristat” to refer to the prodrug rodatristat ethyl in addition to the active moiety.