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FOSTER CITY, Calif. & SHANGHAI—Terns Pharmaceuticals Inc. began the week with the announcement of interim results from its ongoing first-in-human Phase 1 clinical trial of TERN-201 in non-alcoholic steatohepatitis. The drug candidate is a semicarbazide-sensitive amine oxidase (SSAO) inhibitor.
The trial in question is a multiple-phase, single- and multiple-ascending dose study of TERN-201 in healthy individuals, with participants receiving either TERN-201 or placebo in ascending dose cohorts. In the second phase of the study, participants will receive repeat doses of either TERN-201 or placebo in ascending dose cohorts. The primary endpoint for the study is safety and tolerability, with secondary endpoints consisting of pharmacokinetics and pharmacodynamic biomarker assessments of SSAO target engagement.
Interim data showed that single oral doses of TERN-201 were well tolerated, with no significant safety findings or adverse events observed that resulted in discontinuation. Each of the dose levels led to decreases in plasma SSAO activity from baseline, which were maintained up to one week after single dose administrations. The study will now advance to the multiple-dose phase.
"The data observed to date from the Phase 1 clinical study of TERN-201 are encouraging and show that TERN-201 has the potential to be a promising new therapy to treat NASH and liver fibrosis," said Dr. Erin Quirk, chief medical officer of Terns Pharmaceuticals. “Terns has advanced two compounds into clinical development in 2019 with both TERN-201 and TERN-101, an FXR agonist, in ongoing studies. We look forward to seeing further results from the Phase 1 studies of TERN-101 and TERN-201 later in the year as we progress toward our goal of introducing safe and effective combination therapies for NASH."
TERN-201 is one of the compounds Terns Pharmaceuticals is advancing against NASH. As described on the company's website, “SSAO, also known as VAP-1 (Vascular Adhesion Protein-1), is a dual-function amine oxidase which increases oxidative stress through the generation of H2O2 and promotes recruitment of white blood cells in the liver, which results in increased oxidative stress, inflammation and hepatic fibrosis. The level of surface SSAO is upregulated in the vasculature of inflamed tissues, and soluble SSAO levels are elevated in patients with NASH. Inhibition of SSAO is believed to have therapeutic benefit for the treatment of NAFLD, NASH and other chronic fibrotic liver diseases by reducing oxidative stress and recruitment of white blood cells to the liver. TERN-201 has demonstrated potential in a preclinical setting as an SSAO inhibitor which provides an additional treatment mechanism for NASH.”
At the recent EASL 2019 meeting, Terns Pharmaceuticals presented a poster titled “A novel semicarbazide-sensitive amine oxidase inhibitor, TERN-201, reduces NAS and fibrosis in rodent models of non-alcoholic steatohepatitis.” When tested in rat and mouse models, TERN-201 was found to be a potent and selective irreversible SSAO inhibitor in vitro and in vivo. In a rat model of liver disease, the compound suppressed liver fibrosis and inflammation, and also resulted in a dose-dependent reduction in non-alcoholic fatty liver disease activity score in a mouse model of NASH. Additionally, TERN-201 reduced an immune system RNA signature in a mouse model of NASH in a dose-dependent manner, according to the poster.
Eli Lilly and Company originally discovered and developed TERN-201, and Terns Pharmaceuticals inked an exclusive agreement with the company last year to develop, manufacture and commercialize the compound as a treatment for NASH.