January 10, 2020
Terns Pharmaceuticals, Inc., a global biopharmaceutical company focused on discovering and developing innovative therapies to treat non-alcoholic steatohepatitis (NASH) and cancer, today announced the results from an ongoing Phase 1 clinical trial of TERN-201, a semicarbazide-sensitive amine oxidase (SSAO) inhibitor, being developed for the treatment of NASH. These findings were presented today at the NASH-TAG Conference in Park City, Utah, taking place January 9-11, 2020.
The study demonstrated that a single oral dose of TERN-201 resulted in sustained, near-complete suppression of SSAO-specific activity in the plasma. At each dose level studied (1 mg, 3 mg, 6 mg, and 10 mg) this corresponded to >90% inhibition of the SSAO activity in the plasma. These decreases were observed four hours after a single dose of TERN-201 and inhibition was detectable up to one week. No clinically relevant adverse events or laboratory abnormalities were reported.
"The data we have observed from the single-ascending dose phase of our first-in-human clinical study of TERN-201 are very encouraging and show that single doses of TERN-201 result in sustained SSAO inhibition and are very well tolerated," said Erin Quirk, M.D., Chief Medical Officer of Terns. “We remain confident in our approach to SSAO inhibition, and we look forward to sharing the results of the second phase of the study in the near future, which will evaluate the effect of repeat dosing with TERN-201.”
“These clinical data have further validated our belief that TERN-201 can become a valuable new treatment for patients with NASH, who currently have no approved treatment options,” said Weidong Zhong, Ph.D., President and CEO of Terns. “It has been demonstrated that SSAO inhibition can reduce hepatic inflammation and we believe TERN-201 has significant advantages, as it is highly selective for SSAO and which we believe could minimize off-target effects in the NASH patient population."
The first-in-human trial of TERN-201 is a multiple phase, single- and multiple-ascending dose study in healthy human participants. In the first phase, 32 study volunteers receive a single dose of TERN-201 or placebo in ascending dose cohorts. In the second phase of the study, healthy participants receive repeat doses of TERN-201 or placebo, also in ascending dose cohorts. The primary endpoint for each phase of the trial is safety and tolerability. Secondary endpoints include pharmacokinetics (PK) and pharmacodynamic (PD) biomarker assessments of SSAO target engagement.
About 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 pro-inflammatory cells to the liver, which results in increased 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 that could provide a new treatment mechanism for NASH by reducing oxidative stress and recruitment of pro-inflammatory 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.
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 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 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.