Compound Disease Phase
Rodatristat ethyl Pulmonary Arterial Hypertension (PAH) Phase 2
Idiopathic Pulmonary Fibrosis (IPF) Research
Sarcoidosis Research
ALTA-2530 Bronchiolitis Obliterans Syndrome IND Enabling
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)
ALTA-2530 Bronchiolitis Obliterans Syndrome
Next-Generation TPH Inhibitors Oral agents for multiple indications
Alternative routes of administration of multiple indications

Rodatristat – 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, idiopathic pulmonary fibrosis, and potentially sarcoidosis.

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

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.

ALTA-2530 as a treatment for BOS

ALTA-2530 is a novel formulation of recombinant IL-1Ra in development for bronchiolitis obliterans syndrome (BOS) in post-lung transplant patients. As an inhaled medication, ALTA-2530 can be delivered directly to the lungs to achieve higher alveolar levels of IL-1Ra than are feasible with systemic administration.

ALTA-2530 is the only inhaled IL-1Ra being developed to treat respiratory conditions. Inhaled IL1-Ra successfully mitigated BOS progression and provided long-term stabilization of lung function (FEV1) in 3 post-transplant patients with late stage disease (rescue clinical study protocol and personal communication of results: Dr. Roy Levitt, Univ Miami Health System, FL). 

ALTA-2530 is currently in preclinical development for bronchiolitis obliterans syndrome with an IND planned for 2021.  The U.S. FDA granted ALTA-2530 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.

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.