Aligos Therapeutics Presents Strong Chronic Hepatitis B Drug Candidate Portfolio at The Liver Meeting® 2019
- Category: Small Molecules
- Published on Saturday, 09 November 2019 10:34
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Poster presentations demonstrate early preclinical successes of strategically designed, complementary therapies aimed at effecting a functional cure in chronic hepatitis B
SOUTH SAN FRANCISCO, CA, USA I November 08, 2019 I Aligos Therapeutics, Inc. (Aligos), a pre-clinical stage biotechnology company focused on the development of targeted therapies for hepatologic diseases and viral infections, including chronic hepatitis B (CHB), nonalcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC), delivered presentations detailing promising pre-clinical studies today at The Liver Meeting®, hosted annually by the American Association for the Study of Liver Disease (AASLD). The three poster presentations demonstrated promising early results from Aligos’ multi-pronged pipeline of candidates to address CHB, the most common chronic viral infection worldwide.
“Current standards of CHB care fall short of a functional cure for most patients,” explained Leo Beigelman, Ph.D., president of Aligos. “Aligos’ approach is to strategically develop potentially best-in-class drug candidates that target key clinically validated mechanisms of the hepatitis B virus (HBV) life cycle.”
Two presentations demonstrated strong pre-clinical activity for Aligos’ capsid assembly modulator (CAM) candidates—ALG-001075 and ALG-001024—that trigger HBV core proteins to assemble empty, nonviable viral capsids while also inhibiting formation and maintenance of HBV’s covalently closed circular DNA (or cccDNA). In vitro HBV DNA replication studies with the two Aligos CAM compounds demonstrate potent inhibitory activity with EC50 values of 0.54 nM and 2.07 nM for ALG-001075 and ALG-001024, respectively, making these molecules among the most potent CAMs identified to date. In murine studies, both candidates have demonstrated a high degree of efficacy consistent with the potential for once-daily dosing in humans, and warrant further development as potentially best-in-class CAMs. Aligos is developing CAM molecules in collaboration with the laboratory of Raymond Schinazi, Ph.D., D.Sc., FAASLD (Pediatrics) under a license agreement with Emory University.
A third presentation addressed Aligos’ development of proprietary oligonucleotides that inhibit the production of HBsAg (or S-antigen) by a novel mechanism targeting host proteins. HBsAg is a viral encoded protein that suppresses the immune system. Designated S-Antigen Transport-Inhibiting Oligonucleotide Polymers, or STOPs, this class of oligonucleotides is designed to address a barrier to a functional CHB cure: the standard of care targets viral DNA replication but fails to address S-antigen reduction. Preclinical profiling experiments studying the release of HBsAg from HBV-infected cells have shown potent anti-S-antigen activity for Aligos’ ALG-010093, with an EC50 value of 2.5 nM. Mechanism of action studies have demonstrated that STOPs act potentially by affecting protein trafficking from the infected cell, thereby warranting further study.
“We are pleased to be presenting the first publication of the Aligos portfolio at the annual AASLD meeting,” commented Lawrence Blatt, Ph.D., MBA, CEO of Aligos. “We believe we are building a portfolio of compounds that target key aspects of the HBV life cycle that are designed to work in concert and have the potential to benefit patients living with chronic hepatitis B. We have built a team of highly accomplished virologists, oligonucleotide and medicinal chemists, toxicologists, and clinical scientists who are directing their collective talent towards building a functional cure for chronic hepatitis B.”
Aligos Therapeutics, Inc. is a privately held biotechnology company that was founded in 2018 with the mission to become a world leader in the treatment of liver diseases. Aligos is focused on the development of targeted therapies for hepatologic diseases and viral infections, including chronic hepatitis B (CHB), nonalcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC), which collectively affect hundreds of millions of people across the world. 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.
SOURCE: Aligos Therapeutics