Terns Pharmaceuticals to Present Data on Multiple NASH Programs at The Digital International Liver Congress™ 2020

Single doses of TERN-201 were safe and well tolerated and demonstrated potent, selective, and sustained inhibition of SSAO in a Phase 1 clinical trial, with near complete inhibition of plasma SSAO activity observed
TERN-501 demonstrated potent and selective THR-β agonism, and significantly reduced liver steatosis, fibrosis, and serum markers of liver damage in NASH preclinical rodent models

August 21, 2020 14:30

FOSTER CITY, CALIF.--(Business Wire / Korea Newswire) August 21, 2020 -- Terns Pharmaceuticals, Inc., a biopharmaceutical company focused on developing best-in-class, single-agent and combination therapies to treat liver disease, announced today three poster presentations on two lead programs at The Digital International Liver Congress™ 2020, taking place August 27-29, 2020. The presentations include clinical and preclinical data for TERN-201, a semicarbazide-sensitive amine oxidase (SSAO) inhibitor, and in vivo rodent model data for TERN-501, a preclinical thyroid hormone receptor beta (THR-β) agonist, both for the treatment of non-alcoholic steatohepatitis (NASH).

“At the upcoming Digital International Liver Congress, we are excited to share data from multiple studies of our SSAO inhibitor, TERN-201, and the first data for TERN-501, our THR-β agonist, each important mechanisms of action within our Terns' NASH combination strategy,” said Erin Quirk, M.D., President and Chief Medical Officer of Terns. “Clinical data for TERN-201 demonstrate that it has strong target engagement and is generally safe and well tolerated, and indicate that TERN-201 has the potential to impact inflammation and fibrosis in NASH. Both programs also demonstrated strong preclinical data. In rodent models of hypercholesterolemia and fibrotic NASH, TERN-501 rapidly lowered serum cholesterol, reversed liver steatosis and improved liver inflammation and fibrosis, indicating it has the potential to greatly benefit patients as a best-in-class THR-β agonist with potential for use both as a monotherapy, but perhaps more importantly, in combination with our other lead NASH candidates.”

Details of the presentations are as follows:

Presentation Title: Single doses of TERN-201, a novel selective semicarbazide-sensitive amine oxidase (SSAO) inhibitor, are safe, well-tolerated, and result in sustained reduction of SSAO activity in healthy participants
Presentation Number: FRI-088
Session: NAFLD: Therapy
Date: August 28, 2020
Presenter: Martijn Fenaux
Data Highlights:
All dose levels of TERN-201 were safe and well tolerated in healthy subjects with no clinically relevant adverse events reported when administered as a single oral dose ranging from 1 mg to 10 mg. Inhibition of plasma SSAO amine oxidase activity and dose-dependent increases in plasma methylamine (MMA) were sustained up to 1 week after single doses of TERN-201, suggesting potent, covalent target engagement and supporting once daily dosing despite a short plasma half-life.

Poster Title: Anti-inflammatory and anti-fibrotic activity of TERN-201, a semicarbazide-sensitive amine oxidase inhibitor, in a rat choline-deficient high-fat diet non-alcoholic steatohepatitis model
Presentation Number: SAT-032
Session: NAFLD: Experimental and Pathophysiology
Date: August 29, 2020
Presenter: Martijn Fenaux
Data Highlights:

· Dosing with TERN-201 resulted in significant reductions in liver inflammation (p<0.001) and gene expression associated with inflammation in a rat model of NASH.
· TERN-201 also reduced gene expression markers of fibrosis (p<0.005) and liver injury (p<0.05), supporting further development of this drug in patients with NASH.

Poster Title: TERN-501, a potent and selective agonist of thyroid hormone receptor beta, strongly reduces histological features and biomarkers of non-alcoholic steatohepatitis associated pathology in rodent models
Presentation Number: SAT-066
Session: NAFLD: Experimental and Pathophysiology
Date: August 29, 2020
Presenter: Martijn Fenaux
Data Highlights:

· TERN-501 exhibited potent and selective THR-β agonism (THR-β EC50=100nM; THR-α EC50=2,600nM) with good PK properties.
· In a rat hypercholesterolemic model, a robust and dose-dependent reduction in total cholesterol of up to 71% (p < 0.0001 vs. vehicle) was observed.
· In a mouse NASH model, TERN-501 reduced steatosis significantly when compared to control mice. Significant reductions in serum total cholesterol, triglyceride and ALT levels were also observed at all dose levels tested.
· TERN-501 also significantly modulated gene expression in multiple pro-fibrotic stellate cell pathways relevant to the progression of NASH.

About TERN-201 and Semicarbazide-Sensitive Amine Oxidase (SSAO) Inhibition

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. TERN-201 is a potent SSAO inhibitor which provides an additional treatment mechanism for NASH by reducing oxidative stress and recruitment of white blood cells to the liver. TERN-201 is highly specific for SSAO, with a preferential in vitro selectivity index to SSAO over off-target monoamine oxidases (MAO) of >7,000-fold. Certain MAOs could be associated with potential drug-drug interactions in the NASH patient population.

About TERN-501 and Thyroid Hormone Receptor Beta (THR-β)

Thyroid hormone receptor beta (THR-β) is a nuclear hormone receptor that is highly expressed in the liver and plays a central role in lipid metabolism, regulation of blood cholesterol and triglyceride levels, and prevention of steatosis caused by excess fat buildup in the liver. Steatosis is a key driver of NASH, a serious and progressive liver disease characterized by liver inflammation known as steatohepatitis. Small molecule agonists of THR-β represent a promising class of NASH therapies because of their ability to increase metabolism, normalize blood lipid parameters, and reduce steatosis. Terns is pursuing a novel therapeutic approach to selectively activate THR-β in the liver, thereby avoiding potential off-target effects in other tissues. TERN-501 is a highly potent and selective small molecule THR-β agonist.

About NASH

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD), which is caused by the accumulation of excess fat in the liver. NASH is associated with chronic liver inflammation and liver cell injury, and it can lead to fibrosis, cirrhosis, and eventually liver cancer or liver failure. Global rates of NAFLD and NASH are increasing rapidly, in tandem with rising rates of obesity. There is currently no approved medication for the treatment of NASH.

About Terns Pharmaceuticals

Terns Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on developing best-in-class single-agent and combination therapies to treat liver disease including a pipeline of orally administered drug candidates for the treatment of non-alcoholic steatohepatitis (NASH). The company’s liver-selective FXR-agonist, TERN-101, is currently enrolling a multi-center, randomized, double-blind, placebo-controlled Phase 2a clinical trial designed to evaluate efficacy, safety, and pharmacokinetics in 96 presumed NASH patients who receive placebo or TERN-101 at various dose levels for 12 weeks. Terns recently announced positive Phase 1 clinical data for its highly selective SSAO inhibitor, TERN-201, demonstrating potent and sustained target engagement. In addition, the company is actively planning to initiate clinical studies for its thyroid hormone receptor-b agonist TERN-501 as monotherapy and in combination with its other pipeline assets for NASH, as well as advancing its small molecule GLP-1R agonist program. Terns’ investors include OrbiMed, Vivo Capital, Lilly Asia Ventures, and Decheng Capital.

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Website: https://ternspharma.com/

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Contact

Terns Pharmaceuticals, Inc.
US Media Contact:
Investor Relations Contact:
Mark Vignola
investors@ternspharma.com

Media Contact:
Margaret Robinson
info@ternspharma.com

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