Aligos Therapeutics to Present Nonclinical NASH Update at EASL Digital International Liver Congress 2020
SOUTH SAN FRANCISCO, Calif., Aug. 26, 2020 (GLOBE NEWSWIRE) -- Aligos Therapeutics, Inc. (Aligos), a private biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in viral and liver diseases, including chronic hepatitis B (CHB), COVID-19 and therapeutics for nonalcoholic steatohepatitis (NASH), will present nonclinical data related to the company’s thyroid hormone receptor-beta (THR-B) therapeutic program for NASH on August 27 at the European Association for the Study of the Liver (EASL) Digital International Liver Congress™ 2020.
The data, summarized in an abstract titled “Molecular, cellular, and pharmacological characterization of beta-selective partial agonists of human thyroid hormone receptor for the treatment of nonalcoholic steatohepatitis,” will be presented as part of a poster session. Data details a novel series of B- selective THR partial agonists targeting NASH by reducing harmful levels of liver fat without causing the side effects associated with non-selective THR agonists, which can activate the THR-alpha (A) isoform in the heart.
“Following profiling in a panel of in vitro assays, our team assessed the THR activation of several small molecule THR-B agonists in hepatic cells. Promising compounds were then evaluated for efficacy in rats fed with a high fat diet,” said Jerome Deval, Ph.D., senior director of biochemistry at Aligos and lead author of the study. “In contrast to currently known THR-B agonists, the compounds tested show potential for cholesterol reduction in vivo without detectable activation of THR-A.”
In vitro, Aligos’ compounds activated THR-B with an EC50 of approximately 40-60 nM, with a maximum effective amplitude (Emax) of approximately 25-50% relative to the natural thyroid hormone T3. At much higher concentrations (up to 10 µM), the same compounds did not significantly activate THR-A. Further, reporter assays in hepatic (HEK293T) cells demonstrated an Emax value of approximately 55% relative to T3 with no measurable THR-A activation. Aligos’ compounds yielded a >90-fold THR-B/THR-A selectivity index, relative to indices of 1- to 3.4-fold among three existing THR-B agonists. In a diet-induced obese (DIO) rat efficacy model, single doses of B-selective THR partial agonists induced cholesterol reduction, albeit at lower levels compared with full THR agonists.
“Current NASH treatments lack selectivity, supporting our conclusion that there is significant value in pursuing improved candidates as part of Aligos’ portfolio in highly prevalent liver diseases,” said Lawrence Blatt, Ph.D., MBA, chief executive officer of Aligos. “We believe that these compounds warrant further study.”
Aligos Therapeutics, Inc. is a privately held biopharmaceutical company that was founded in 2018 with the mission to become a world leader in the treatment of viral infections and liver diseases. Aligos is focused on the development of targeted antiviral therapies for chronic hepatitis B (CHB) and COVID-19 as well as leveraging its expertise in liver diseases to create targeted therapeutics for NASH. Aligos’ strategy is to harness the deep expertise and decades of drug development experience its workforce has in liver disease, particularly viral hepatitis, to rapidly advance its pipeline of best-in-class molecules.
Please visit www.aligos.com for more information.
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