Compound Disease Phase
Rodatristat Ethyl Pulmonary Arterial Hypertension (PAH) Now Enrollling Phase 2
Idiopathic Pulmonary Fibrosis (IPF) Phase 2 Ready
Sarcoidosis Phase 2 Ready
Next-Generation TPH Inhibitors Oral agents for multiple indications Research
Alternative routes of administration for multiple indications Research
CompoundDiseaseResearchIND EnablingPhase 1Phase 2Phase 3
Rodatristat Ethyl Pulmonary Arterial Hypertension (PAH)
Idiopathic Pulmonary Fibrosis (IPF)
Next-Generation TPH Inhibitors Oral agents for multiple indications
Alternative routes of administration of multiple indications

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, idiopathic pulmonary fibrosis, and potentially sarcoidosis.

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.

Rodatristat – a Peripherally Acting TPH Inhibitor

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 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

Healthy pulmonary artery in rat
Pulmonary artery in rat with PAH
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.

Next – Generation TPH Inhibitors

Altavant has an active preclinical research program to discover and develop 3rd generation TPH1 inhibitors that have different product profiles or that feature different routes of administration. Potential improvements to the 3rd generation compounds include increasing potency against TPH1 and modification of the molecules’ physiochemical properties to increase bioavailability of the drug. With this program, we believe Altavant can harness the full potential of TPH1 inhibitors in treating human disease.

You can learn more about our Elevate 1 clinical trial now enrolling by visiting our study website. Additional study details can be found on our posting

For references related to experimental approaches to treat PAH and clinical articles specifically related to rodatristat, please visit our Publications page. *For ease of reading, this website sometimes uses the name “rodatristat” to refer to the prodrug rodatristat ethyl in addition to the active moiety.