|Rodatristat ethyl||Pulmonary Arterial Hypertension (PAH)||Phase 2|
|Idiopathic Pulmonary Fibrosis (IPF)||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|
|Compound||Disease||Research||IND Enabling||Phase 1||Phase 2||Phase 3|
|Rodatristat Ethyl||Pulmonary Arterial Hypertension (PAH)|
|Idiopathic Pulmonary Fibrosis (IPF)|
|ALTA-2530||Transplant-associated bronchiolitis obliterans syndrome|
|Chemical-induced bronchiolitis obliterans syndrome|
* Partnered with BARDA
|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
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 and Chemical Lung Injury
ALTA-2530 is a novel inhaled formulation of recombinant IL-1Ra in development for bronchiolitis obliterans syndrome (BOS), which can arise following lung transplant or as a result of inhaled exposure to noxious chemicals. As an inhaled medication, ALTA-2530 can be delivered directly to the lungs to achieve higher levels of IL-1Ra in bronchioles than are feasible with systemic administration.
ALTA-2530 is the only inhaled IL-1Ra being developed to treat respiratory conditions. Inhaled IL1-Ra has been used in a small human study with positive results. Data from this study will be shared at a future medical meeting.
Altavant anticipates submitting an IND in 2023 to commence a clinical study with ALTA-2530 in post-lung transplant patients suffering from bronchiolitis obliterans syndrome. In addition, the company has partnered with the Biomedical Advanced Research and Development Authority (BARDA) and the National Institute of Allergy and Infectious Diseases (NIAID) at the US Department of Health and Human Services (HHS) to investigate the utility of ALTA-2530 for the treatment of acute and chronic chemical lung injuries caused by the inhalation of sulfur mustard. This research is funded under the government’s Chemical Countermeasures Research Program (CCRP). The CCRP is responsible for overseeing the research and development of medical countermeasures that could prevent lethality and/or treat injuries resulting from toxic chemical exposure. The U.S. FDA granted ALTA-2530 orphan status for bronchiolitis obliterans syndrome 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.