Aligos Therapeutics to Present Nonclinical Data for All Components of Chronic Hepatitis B Combination Therapy at EASL Digital International Liver Congress 2020
SOUTH SAN FRANCISCO, Calif., Aug. 27, 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 NASH, will present four abstracts highlighting nonclinical data for drug candidates in the company’s CHB portfolio at the European Association for the Study of the Liver (EASL) Digital International Liver Congress™ 2020.
“Taken together, our findings show promising progress across our chronic hepatitis B portfolio, both individually and in pairwise combinations,” said Lawrence Blatt, Ph.D., MBA, chief executive officer of Aligos. “As our lead candidates advance in the clinic, we are gratified to see that our approach of designing purpose-built drug candidates targeting clinically validated mechanisms of action have shown promising activity in our nonclinical studies to date.”
The presentations provide new information for many of the company’s classes of drug candidates designed for use in combination therapy to develop high rates of functional cure in CHB. Of note, an abstract related to Aligos’ STOPSTM program, entitled “Structural requirements for ’S-antigen transport-inhibiting oligonucleotide polymer inhibition of hepatitis B surface antigen secretion,” was selected for inclusion in the meeting’s ‘Best of ILC’ category, which highlights the most noteworthy contributions to the meeting’s scientific program. The titles of each abstract, the class(es) of candidates highlighted and the findings are as follows:
S-antigen Transport-inhibiting Oligonucleotide PolymerS (STOPSTM)
Title: Structural requirements for S-antigen Transport-inhibiting Oligonucleotide Polymer inhibition of hepatitis B surface antigen secretion
Summary: Aligos’ proprietary STOPS candidates were evaluated for S-antigen (or HBsAg) reduction and cytotoxicity in cell culture to optimize activity relative to structurally similar nucleic acid polymers (NAPs). Upon varying sequence, length, and chemical modifications of STOPS, it was found that STOPS’ activity is dependent on length, with the highest potency observed at over 34 nucleotides. Sequence was critical for STOPS activity: when the AC dinucleotide repeat was changed to AG, the antiviral activity was completely lost. However, activity was retained when the base identities were maintained, such as with a CA repeat. Site-specific incorporation of backbone chemistries such as a stereospecific phosphorothioate bond also improved potency.
Note: This abstract will be available publicly after the meeting as part of EASL’s ‘Best of ILC’ summary slide deck.
Capsid Assembly Modulators (CAMs)
Title: ALG-000184, a prodrug of capsid assembly modulator ALG-001075, demonstrates best-in-class preclinical characteristics for the treatment of chronic hepatitis B
Summary: ALG-001075 was found to be a potent inhibitor of HBV DNA production in HepG2.117 cells with EC50/EC90 values of 0.63/3.17 nM (n = 12), respectively. This level of potency exceeds that of all other known reported CAMs that have entered clinical development, efficiently blocking both HBV genome encapsidation and de novo cccDNA formation. ALG-000184, a prodrug of ALG-001075, showed improved pharmacokinetic properties, including improved aqueous solubility, stability and oral absorption across species with efficient conversion to ALG-001075 in vivo.
Antisense oligonucleotides (ASOs)
Title: Best in class hepatitis B virus anti-sense oligonucleotides: Next generation bridged nucleic acid chemistries significantly improve the therapeutic index by reducing hepatotoxicity and increasing in vivo efficacy in a mouse model
Summary: Although locked nucleic acid (LNA)-modified ASOs can cause liver toxicity, applying bridged nucleic acid and nucleobase gap modifications to LNA ASOs showed improved efficacy and reduced liver toxicity in a mouse model of hepatitis B virus (HBV) infection, suggesting that Aligos’ anti-HBV ASO candidates have potential to be best in class compounds.
STOPS in combination with other agents
Title: Combination drug interactions of hepatitis B virus (HBV) S-antigen Transport-inhibiting Oligonucleotide Polymers in vitro
Summary: STOPS in combination with nucleos(t)ides, core assembly modulators (CAMs), and HBV-specific antisense oligonucleotides (ASOs) were evaluated for inhibition of HBV replication and HBsAg release in HBV-producing hepatic cells. When tested in pairwise combinations with the other HBV inhibitors, STOPS demonstrated synergy or additivity. Overall, the activity of STOPS warrants further study as a component of a combination therapy in CHB.
About Chronic Hepatitis B (CHB)
CHB is a major cause of chronic liver disease that the World Health Organization estimates affects ~257 million people worldwide, more people than hepatitis C virus (HCV) and HIV infection combined. Serious complications of CHB include cirrhosis and liver cancer, which are associated with significant mortality. Approximately 900,000 people died from CHB-related causes in 2015 alone and the mortality rate has been rising for decades. Although current standard of care for patients with CHB is effective in suppressing HBV, it is associated with very low rates of functional cure, which is the main goal of CHB treatment.
Aligos Therapeutics, Inc., is a privately held, clinical stage 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 coronaviruses as well as leveraging its expertise in liver diseases to create targeted therapeutics for nonalcoholic steatohepatitis (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 potentially best-in-class molecules.
Please visit www.aligos.com for more information.
Amy Jobe, Ph.D.
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Corey Davis, Ph.D.
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