Terns Pharmaceuticals, Inc. today announced presentation of preclinical data on its two lead programs at The International Liver Congress„¢ 2019, the Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria, April 10-14. TERN-101 reduced liver steatosis, inflammation, ballooning, and fibrosis in a preclinical model of non-alcoholic steatohepatitis (NASH) and TERN-201 reduced non-alcoholic fatty liver disease (NAFLD) activity score (NAS) and fibrosis in preclinical models of NASH.
We believe TERN-101 and TERN-201 have the potential to be meaningful new treatments for NASH, a condition with no existing treatment options, and the data we are presenting at EASL reinforces our confidence, said Erin Quirk, M.D., Chief Medical Officer of Terns. Both of our lead programs remain on track to generate clinical data in 2019, and we look forward to continuing our work towards our goal of developing effective and safe combination therapies for patients with NASH and liver fibrosis.
Details of the presentations are as follows:
Title: A novel farnesoid X receptor agonist, TERN-101, reduces liver steatosis, inflammation, ballooning, and fibrosis in a murine model of non-alcoholic steatohepatitis Presentation Number: FRI-313 Session: Poster: NAFLD: Experimental and pathophysiology Date / Time: Friday, April 12, 9 a.m. – 5 p.m. CEST Presenter: Dr. Kevin Klucher
Title: A novel Semicarbazide-Sensitive Amine Oxidase inhibitor, TERN-201, reduces NAS and fibrosis in rodent models of non-alcoholic steatohepatitis Presentation Number: FRI-314 Session: Poster: NAFLD: Experimental and pathophysiology Date / Time: Friday, April 12, 9 a.m. – 5 p.m. CEST Presenter: Dr. Kevin Klucher
Key highlights from the poster A novel farnesoid X receptor agonist, TERN-101, reduces liver steatosis, inflammation, ballooning, and fibrosis in a murine model of non-alcoholic steatohepatitis:
- TERN-101, when administered in diet-induced obese (DIO) models of NASH, caused a dose-dependent increase in FXR-mediated gene expression, showing on-target activity, and induced pathways that modulate lipid metabolism, inflammation, and fibrosis.
- All doses of TERN-101 markedly reduced the NAFLD activity score, demonstrating reductions in liver steatosis, hepatocellular ballooning, inflammation, and triglycerides.
- Liver fibrosis was significantly reduced by all dose levels of TERN-101.
Key highlights from the poster A novel Semicarbazide-Sensitive Amine Oxidase inhibitor, TERN-201, reduces NAS and fibrosis in rodent models of non-alcoholic steatohepatitis:
- NAFLD activity score was reduced by TERN-201 treatment, with a 42% reduction from baseline at 20 mg/kg, primarily driven by a reduction in hepatocellular ballooning (80% reduction from baseline).
- TERN-201 significantly reduced liver inflammation and fibrosis in a preclinical fibrosis model.
Farnesoid X Receptor (FXR) Agonism and TERN-101
FXR is a nuclear receptor that is highly expressed in the liver and small intestine. Bile acids (BA) are natural ligands of FXR, and their binding with and activation of FXR is critical to the regulation of cellular pathways that modulate BA synthesis, lipid metabolism, inflammation and fibrosis. It is believed by many in the scientific community that FXR agonism and activation has potential as a new treatment modality for nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). TERN-101 is a potent non-bile acid FXR agonist being developed as a therapeutic for NASH.
Semicarbazide-Sensitive Amine Oxidase (SSAO) Inhibition and TERN-201
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.
About Terns Pharmaceuticals
Terns Pharmaceuticals, Inc. is a clinical-stage pharmaceutical company that is focused on the discovery and development of medicines for chronic liver disease and cancer. Based in China and the United States, the company is advancing a pipeline of small molecule drug candidates for the treatment of non-alcoholic steatohepatitis (NASH) and cancer, across multiple modalities. Terns leverages world class expertise in disease biology, medicinal chemistry, and clinical development, in order to bring promising new therapies to patients in China and other global markets.
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