Terns Reports Positive Top-line Results from Phase 1 Proof of Concept Clinical Trial of THR-β agonist TERN-501

TERN-501 demonstrated significant effects on key pharmacodynamic marker of THR-β engagement linked to NASH histologic efficacy

TERN-501 was generally safe and well-tolerated with predictable pharmacokinetic profile with low variability

Terns plans to initiate first FXR/THR-β agonist combination trial in NASH in 1H 2022

FOSTER CITY, Calif., Nov. 09, 2021 (GLOBE NEWSWIRE) -- Terns Pharmaceuticals, Inc. (“Terns” or the “Company”) (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule single-agent and combination therapy candidates for the treatment of non-alcoholic steatohepatitis (NASH) and other chronic liver diseases, today reported positive top-line results from a Phase 1 clinical trial of TERN-501, a thyroid hormone receptor beta (THR-β) agonist in development for the treatment of patients with NASH.

The Phase 1 clinical trial includes single ascending dose (SAD), multiple ascending dose (MAD) and drug-drug interaction (DDI) cohorts evaluating the safety, tolerability, pharmacodynamics (PDs) and pharmacokinetics (PKs) of TERN-501. Healthy volunteers with mildly elevated low-density lipoprotein (LDL) cholesterol were randomized to placebo (n=2) or TERN-501 (n=6) in each cohort. Volunteers randomized to TERN-501 received single doses of 3, 10, 30 or 60 mg of TERN-501 in the SAD portion of the study or multiple doses of 3, 6 or 10 mg of TERN-501 once daily for 14 days in the MAD portion of the study. In the DDI portion of the study, volunteers received open label TERN-501 co-administered with TERN-101, the Company’s liver-distributed farnesoid X receptor (FXR) agonist also in development for the treatment of NASH.

TERN-501 was generally safe and well-tolerated in the SAD and MAD cohorts with a similar incidence of adverse events (AEs) across all TERN-501 treatment groups and placebo. All AEs were mild to moderate with no apparent dose relationship. There were no treatment-emergent serious AEs (SAEs) and no volunteer discontinued TERN-501 or the study due to any AE. There were no cardiac safety signals, no incidence of diarrhea and no differences between TERN-501 dose groups and placebo in change from baseline in heart rate, blood pressure or other vital signs. Thyroid function test results were consistent with other THR-β agonists currently in clinical development, and there were no findings of clinical hyper- or hypo-thyroidism. There were no clinically meaningful differences between placebo and any TERN-501 dose group in liver function abnormalities or mean change from baseline in liver transaminases at Day 15 in the MAD cohorts.

In the SAD and MAD cohorts, TERN-501 demonstrated a predictable PK profile with low variability. Study drug plasma exposures were linear and approximately dose-proportional with no overlap between dose strengths. There was no significant accumulation of drug over 14 days of dosing. TERN-501 plasma half-life was greater than 13 hours in all single and repeat dose cohorts, supporting once-daily dosing. The overall PK profile indicates TERN-501 is well-suited for co-formulation with other small molecule NASH agents as an oral, once-daily fixed dose combination.

Significant effects on sex hormone binding globulin (SHBG), a key PD marker of THR-β engagement linked to NASH histologic efficacy, were observed following treatment with TERN-501. As further described in the table below, SHBG increases observed with 14 days of TERN-501 treatment were significant, dose dependent, and have been associated with robust reductions in MRI proton density fat fraction (MRI-PDFF) and NAFLD Activity Score in a precedent late-stage clinical NASH trial.

In addition, significant reductions were observed in atherogenic lipids including LDL cholesterol and apolipoprotein B (Apo-B), comparable to or greater than those observed in Phase 1 studies of other THR-β agonists being studied in late-stage clinical trials. All TERN-501 dose groups demonstrated significant decreases in LDL cholesterol compared to placebo during the dosing period. The maximum mean LDL cholesterol decreases over the treatment period were -22%, -28% and -27% for 3, 6 and 10 mg doses, respectively, compared to placebo (-8%).

The PD results from these MAD cohorts are summarized below:

Note: Day 15 represents 24 hours following the last dose of TERN-501* p-value vs. placebo: