Terns Pharmaceuticals Highlights TERN-501 Phase 1 Clinical Trial Results at AASLD The Liver Meeting® 2022 | small molecules

Terns Pharmaceuticals Highlights TERN-501 Phase 1 Clinical Trial Results at AASLD The Liver Meeting® 2022 |  small molecules

Terns Pharmaceuticals Highlights TERN-501 Phase 1 Clinical Trial Results at AASLD The Liver Meeting® 2022

The data demonstrated that treatment with TERN-501 resulted in time- and dose-dependent increases in sex hormone binding globulin (SHBG), a key marker related to the histological efficacy of NASH.

Phase 2a DUET trial evaluating TERN-501 alone and in combination with TERN-101, the first trial evaluating both THR-β and FXR agonists in NASH, is ongoing

FOSTER CITY, CA, USA I November 04, 2022 I Terns Pharmaceuticals, Inc. (“Terns” or the “Company”) (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small molecule product candidates to treat serious diseases, including oncology, obesity and non-alcoholic steatohepatitis. (NASH), today announced that the company is reporting positive clinical data from its Phase 1 study of TERN-501, a thyroid hormone receptor beta agonist (THR-β) in development for the treatment of NASH. Results are highlighted in a poster presentation at The Liver Meeting®the annual meeting of the American Association for the Study of Liver Diseases (AASLD), which will take place from November 4 to 8, 2022.

The poster presentation, by Cara Nelson, Ph.D., senior director of clinical pharmacology at Terns, highlights the results of 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. The results showed that among the 24 treated participants, TERN-501 was generally well tolerated and exhibited dose-dependent pharmacokinetics with low variability. Participants treated with TERN-501 also experienced time-dependent increases in sex hormone binding globulin (SHBG), a key pharmacodynamic marker of THR-β compromise related to decreases in atherogenic lipid levels and histologic efficacy of NASH. and dose and highly associated with exposure to TERN-501. 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 increases in SHBG ≥ 75% at day 15 compared to baseline.

In TERN-501 recipients, results also showed dose-dependent decreases in total cholesterol, LDL cholesterol, and apolipoprotein-B levels, with greater mean percent decreases at day 15 in recipients who had SHBG increases ≥ 75 % than those who had < 75% Increases in SHBG and placebo recipients.

“The presented data from our Phase 1 study reiterate that TERN-501 has a predictable pharmacokinetic profile with low variability and treatment results in robust increases in SHBG and lipid-lowering effects. TERN-501 is a promising candidate for the treatment of NASH, either as a monotherapy or in combination with other agents,” said Kerry Russell, MD, Ph.D., medical director of Terns. “We look forward to continuing evaluations of TERN-501, including our ongoing phase 2a DUET trial of TERN-501, alone and in combination with our FXR agonist TERN-101, with first-line data expected in the second half of 2023. ”.

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 to evaluate the safety and efficacy of a THR-β agonist and farnesoid X receptor (FXR) agonist combination regimen in patients with NASH. 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 over 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.

About Terns Pharmaceuticals
Terns Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing a portfolio of small molecule product candidates to address serious diseases including oncology, obesity and NASH. Terns’ pipeline includes four clinical-stage development programs including a BCR-ABL allosteric inhibitor, a THR-β agonist, an FXR agonist, a VAP-1 inhibitor, and a receptor agonist preclinical program. small molecule GLP-1. For more information please visit: www.ternspharma.com.

About TERN-501
TERN-501 is a thyroid hormone receptor beta (THR-β) agonist with high metabolic stability, improved hepatic distribution, and higher selectivity for THR-β compared to other THR-β agonists in development. THR-β agonism increases fatty acid metabolism through mitochondrial oxidation and affects cholesterol synthesis and metabolism. As a result, THR-β stimulation has the ability to reduce hepatic steatosis and improve serum lipid parameters, including LDL cholesterol and triglycerides. Terns reported single ascending and multiple ascending positive dose (SAD/MAD) data of phase 1 proof-of-concept clinical trial in November 2021. Phase 2a clinical trial of DUET of TERN-501 alone and in combination with TERN-101 is ongoing, with first-line data expected in the second half of 2023.

About TERN-101
TERN-101 is a non-bile acid-containing, liver-distributing FXR agonist that has demonstrated a differentiated tolerability profile and better target interaction, likely due to its sustained activation of FXR in the liver, but only because of its sustained activation of FXR in the liver. a transient activation of FXR in the intestine. FXR is a nuclear receptor that is expressed primarily in the liver, intestine, and kidneys. FXR regulates the hepatic expression of several genes involved in lipid metabolism, inflammation, and fibrosis. Clinical studies of other FXR agonists have shown significant histologic improvements in NASH, but have also resulted in pruritus, adverse lipid changes, and discontinuations. Terns reported positive results results of the Phase 2a LIFT study of TERN-101 in June 2021.

FONT: Pharmaceutical Terns

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