Potential Therapy for IPF, PAT-1251, Seen To Be Safe and Well-Tolerated in Phase 1 Trial


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A first clinical trial of the safety and tolerability of a potential treatment for idiopathic pulmonary fibrosis (IPF) and other fibrotic diseases —  PAT-1251, being developed by PharmAkea — was successfully completed in healthy volunteers, the company announced.

PAT-1251 is an investigational small-molecule designed to specifically inhibit the LOXL2 enzyme. Patients with fibrotic illnesses, including IPF or fibrosis associated with the hepatitis B- and hepatitis C viruses, often have higher-than-normal levels of LOXL2 in the blood.

This enzyme promotes the cross-linking of collagen and elastin, making the extracellular matrix more resistant to degradation but also more stiff. Such change triggers a cascade of signals that can initiate pro-fibrotic mechanisms, and ultimately leads to scarring and destruction of normal tissue.

Given its importance in the fibrotic process, blocking LOXL2 is an attractive therapeutic strategy to diseases in which fibrosis is a main feature.

“Based on its unique mechanism of action, PharmAkea’s LOXL2 inhibitor, PAT-1251, has the potential to improve lung function in patients suffering from IPF, a debilitating lung disorder in which novel agents with improved tolerability, efficacy, and long-term safety profiles are needed,” Robert Williamson, CEO of PharmAkea, said in a press release.

The aim of the Phase 1 trial (NCT02852551) was to evaluate the safety, tolerability, stability, and distribution in the body of the inhibitor, given as an oral solution or a tablet. A total of 48 healthy volunteers received either single or multiple, ascending doses of PAT-1251 (up to 4,000 mg in the single-dose group and up to 2,000 mg over seven days in the multiple-dose group). A placebo was given to 16 people who served as controls.

Preliminary results show that PAT-1251 was safe and well-tolerated by the participants, and an assay of blood samples confirmed that PAT-1251 was able to bind as intended to LOXL2 in plasma. Ten people reported mild treatment-related side effects, primarily nausea and headaches. Further data analysis will allow determination of an optimal dose to be used in further clinical testing.

These results were presented in a poster titled “PAT-1251, a Mechanism-Based Small Molecule Inhibitor of LOXL2, as a Potential Anti-Fibrotic Treatment for IPF” during the IPF Summit, held in Boston on Aug. 21–23.

The company expects to finish an analysis of long-term toxicology data by year’s end. The results will support a Phase 2 study of PAT-1251 in IPF patients, planned for the beginning of 2018.

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