Terns Pharmaceuticals, Inc. announced that the company is presenting positive clinical data from its Phase 1 study of TERN-501, a thyroid hormone receptor beta (THR-ß) agonist in development for the treatment of NASH. The results are being highlighted in a poster presentation at The Liver Meeting®, the annual meeting of the American Association for the Study of Liver Diseases (AASLD), taking place November 4-8, 2022. The poster presentation, delivered by Cara Nelson, Ph.D., senior director of clinical pharmacology at Terns, highlights results from a Phase 1 study in which healthy participants with low-density lipoprotein (LDL) cholesterol levels of 100-190 mg/dL were randomized (3:1) to receive TERN-501 (1, 3, 6, or 10 mg) or placebo once daily for 14 days.

Results showed that among the 24 treated participants TERN-501 was generally well tolerated and exhibited dose-dependent pharmacokinetics with low variability. TERN-501-treated participants also experienced increases in sex-hormone binding globulin (SHBG), a key pharmacodynamic marker of THR-ß engagement linked to decreases in levels of atherogenic lipids and NASH histologic efficacy, which were time- and dose-dependent and highly associated with TERN-501 exposure. Results showed that 0%, 0%, 33.3%, 83.3%, and 100% of subjects in the placebo, TERN-501 1, 3, 6, and 10 mg groups, respectively, had = 75% SHBG increases at Day 15 compared to baseline.

In TERN-501 recipients, results also showed dose-dependent decreases in levels of total cholesterol, LDL cholesterol and apolipoprotein-B, with greater median percent decreases at Day 15 in recipients who had = 75% SHBG increases than those who had < 75% SHBG increases and placebo recipients. Terns will review the ongoing Phase 2a DUET trial (NCT05415722) design and objectives in a second presentation at The Liver Meeting. DUET is the first trial assessing the safety and efficacy of a THR-ß agonist and a farnesoid X receptor (FXR) agonist combination regimen in NASH patients.

The DUET trial will evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of TERN-501 administered alone and in combination with TERN-101 in approximately 140 non-cirrhotic NASH patients for 12 weeks. The primary endpoint will be the relative change in liver fat content as measured by MRI protein density fat fraction (PDFF) at Week 12 for TERN-501 monotherapy compared to placebo.