Cary, NC — APIE Therapeutics, a preclinical pharmaceutical company pioneering novel and proprietary drugs to activate the apelin receptor (APJ), presented evidence that agonism of the apelinergic system (APJ/apelin axis) triggers the repair of damaged pulmonary vascular endothelial cells. Through this novel mechanism of action, APIE Tx’s lead experimental drug candidate, APT-101 may have therapeutic benefit in the treatment of fibrotic lung diseases caused by the breakdown of the vascular endothelial niche, an endothelial cell barrier that protects the alveoli and promotes oxygen exchange.
APIE Tx is developing APT-101, a small molecule designed to bind selectively and preferentially to APJ, for the treatment of fibrotic diseases such as systemic sclerosis-associated lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF). APT-101 was granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of IPF.
“Since the discovery of apelin in 1998, interest in the apelinergic system and its role in the repair and maintenance of vascular health has increased dramatically, stated Esther M. Alegría, Ph.D., founder and CEO of APIE Therapeutics. “We are on the leading edge of drug discovery in this therapeutic area. Our small molecule candidate, APT-101 has shown the potential to protect the vascular endothelium from damage and also regenerate damaged lung tissue in animal models of pulmonary fibrosis. We are eager to advance APT-101 into the clinic where we can assess its therapeutic impact on patients living with pulmonary fibrosis such as interstitial lung disease (ILD).”
The apelinergic system plays a key role in the maintenance of vascular health and function through regulation of fibrosis, cell proliferation and inflammation. Independent research shows that the apelin receptor, APJ is highly expressed in the pulmonary vascular endothelium and is upregulated in ILD in response to disease factors. Further, activation of the apelinergic system through APJ has been shown to regenerate the small capillary blood vessels that are damaged by inflammation and fibrosis, which are characteristic of ILD. These findings support the beneficial role of the apelinergic system in ILD and the development of an APJ agonist to activate these regenerative pathways.
APT-101 is an orally bioavailable small molecule that selectively and potently targets APJ. In animal models of pulmonary fibrosis, APIE Tx has demonstrated that APT-101 diminishes the onset of fibrosis when administered before its onset and reduces collagen buildup and fibrosis when administered following pulmonary damage. The mechanism by which APT-101 exerts its therapeutic effect is through the normalization of key pathways involved in the health of vascular endothelial cells. Preclinical data presented at IPF Summit show that APT-101 normalizes the expression of endothelial nitric oxide synthase (eNOS), which is involved in maintenance of cell permeability and vascular function, and tissue metalloproteinase (TMP1), which is involved in regulation of fibrogenesis.
|Repair and Regeneration of Vascular Endothelium as a Target for the Treatment of Lung Fibrosis
|Robert N. Willette, PhD; Scott Runyon, PhD; Ronnie Maitra, PhD; Esther Alegria, PhD
|August 30, 2022 at 3:30 pm ET
The IPF Summit is a Hanson Wade conference taking place August 29-September 1, 2022 in Boston, MA. A copy of the poster may be found on the company website following the conclusion of the conference.
About APIE TherapeuticsAPIE Therapeutics is a preclinical stage pharmaceutical company pioneering the development of a portfolio of small-molecule therapeutic drugs that target the apelinergic signaling pathway to repair and regenerate, post injury, the vasculature niche, which is associated with the pathophysiology of many chronic fibrotic diseases. APIE Therapeutics licensed a portfolio of compounds from RTI International, a well-known nonprofit research institute and inventors of commercial drugs such as Taxol®, Camptothecin®, EllaOne® and Esmya®.
The company’s lead candidate, APT-101 was granted Orphan Drug Designation (ODD) by the U.S. FDA as a potential treatment of idiopathic pulmonary fibrosis (IPF). The company is on track to file an IND application with the U.S. FDA to commence a clinical program for the treatment of patients with systemic sclerosis (SSc), including those who have progressed to interstitial lung disease (SSc-ILD). Systemic sclerosis, sometimes referred to as systemic scleroderma, is a progressive systemic disease of unknown cause characterized by fibrotic scaring in major organ systems including the skin and kidneys. Patients often progress to develop ILD, which is the leading cause of early death for patients with SSc. Currently there are no disease-modifying treatments for these patients, representing a critical unmet medical need for this orphan disorder.