Aligos Therapeutics Presents Positive Data at the EASL Congress 2025

Rhea-AI Summary

Aligos Therapeutics (NASDAQ: ALGS) presented positive data from eight presentations at EASL Congress 2025, highlighting significant progress in their liver disease pipeline. The 96-week data for ALG-000184 showed remarkable results in chronic hepatitis B treatment, with 100% of subjects achieving HBV DNA viral suppression. In HBeAg+ subjects, 9/9 achieved HBV DNA suppression by Week 96, while all HBeAg- subjects (11/11) showed rapid decline and sustained suppression by Week 24.

Additionally, their THR-β agonist ALG-055009 demonstrated strong potential in MASH treatment, showing up to 46.2% placebo-adjusted median relative reductions in liver fat at Week 12. Notably, 11/14 subjects on stable GLP-1 agonists treated with ALG-055009 showed liver fat decreases, while maintaining a favorable tolerability profile with gastrointestinal-related adverse events similar to placebo.

Positive

• 100% of subjects achieved HBV DNA viral suppression with ALG-000184 by Week 96
• No viral breakthrough observed in any chronic HBV infection subjects for up to 96 weeks
• Up to 46.2% placebo-adjusted reduction in liver fat with ALG-055009
• Favorable tolerability profile demonstrated in both drug candidates
• Significant improvements in atherogenic lipids achieved with ALG-055009

Negative

• None.

Insights

Biotech Clinical Analyst

Aligos shows impressive 96-week HBV suppression data and strong MASH results, advancing two promising therapies in areas with significant unmet needs.

The 96-week data for ALG-000184 in chronic HBV infection demonstrates remarkable antiviral potency. The press release reports that 100% of both HBeAg+ and HBeAg- subjects achieved HBV DNA suppression below lower limit of quantification (10 IU/mL). This is particularly noteworthy in the HBeAg+ population, which had extremely high baseline viral loads of 8.0 log10 IU/mL - a population typically challenging to treat.

What distinguishes ALG-000184 from standard nucleoside/nucleotide analogs is the concurrent reduction in viral antigens (HBsAg, HBeAg, and HBcrAg). These reductions suggest potential impact on cccDNA (closed circular DNA), which is the persistent form of the virus in liver cells and a key barrier to achieving functional cure. Additionally, no viral breakthrough or resistance mutations were detected through 96 weeks of monotherapy, suggesting a high genetic barrier to resistance.

For ALG-055009 in metabolic dysfunction-associated steatohepatitis (MASH), the data reveals placebo-adjusted median relative reductions in liver fat of up to 46.2% as measured by MRI-PDFF at 12 weeks. Notably, the compound showed efficacy even in patients already on GLP-1 receptor agonists – 11/14 GLP-1 users receiving ALG-055009 had liver fat decreases, while 4/4 GLP-1 users on placebo saw increases. This suggests potential complementary effects beyond what GLP-1s alone can achieve.

The improvements in atherogenic lipids, including lipoprotein(a), point to potential cardiovascular benefits beyond hepatic effects. This broader cardiometabolic profile could differentiate ALG-055009 from other MASH therapies currently in development.

Hepatology Specialist

These clinical results represent significant developments for two major liver diseases with substantial unmet needs. For chronic HBV, current standard treatments rarely achieve functional cure, requiring indefinite therapy. ALG-000184, a capsid assembly modulator with enhanced mechanism (CAM-E), shows superior viral suppression characteristics compared to what we typically achieve with nucleos(t)ide analogs alone.

The complete suppression of HBV DNA in 100% of both patient populations by week 96 is clinically meaningful, but what's truly intriguing is the multi-log reductions in viral antigens. HBcrAg (hepatitis B core-related antigen) decline is particularly significant as it correlates with intrahepatic cccDNA activity. The data suggests ALG-000184 may not merely suppress viral replication but potentially interfere with the establishment of new cccDNA, which is crucial for any strategy targeting functional cure.

For MASH treatment, the THR-β agonist ALG-055009 shows robust hepatic de-fatting effects consistent with its mechanism. The 46.2% placebo-adjusted reduction in liver fat positions it among the more potent agents in development. The efficacy demonstrated on top of GLP-1 therapy is clinically relevant, as many MASH patients are increasingly being treated with GLP-1 receptor agonists for metabolic comorbidities.

The simultaneous improvement in atherogenic lipids addresses an important aspect of MASH management – cardiovascular risk reduction. MASH patients have elevated cardiovascular mortality, and improvements in lipid profiles could translate to meaningful clinical outcomes beyond liver health.

Both compounds demonstrated favorable tolerability profiles through their respective treatment durations, which is essential for diseases requiring long-term therapy. The absence of THR-α mediated cardiac effects with ALG-055009 (implied by its described safety profile) is particularly important for this class of compounds.

SOUTH SAN FRANCISCO, Calif., May 08, 2025 (GLOBE NEWSWIRE) -- Aligos Therapeutics, Inc. (Nasdaq: ALGS), a clinical stage biopharmaceutical company focused on improving patient outcomes through best-in-class therapies for liver and viral diseases, today announced positive data from eight presentations at the European Association for the Study of the Liver (EASL) Congress 2025, being held May 7 – 10, 2025 in Amsterdam, Netherlands.

“We are pleased to have eight presentations at this year’s EASL Congress from programs across our pipeline,” stated Lawrence Blatt, PhD, MBA, Chairman, President, & CEO of Aligos Therapeutics. “In particular, we are excited to share an update on the 96-week data from the monotherapy cohort receiving 300 mg ALG-000184. All subjects in both the HBeAg⁺ and HBeAg^- cohorts have achieved HBV DNA viral suppression < LLOQ (10 IU/mL) and continue to demonstrate sustained log₁₀ reductions in viral antigens such as HBcrAg. These data further strengthen our belief that ALG-000184 is a first-/best-in-class asset with the potential to improve patient outcomes. Additionally, we will present biomarker and subgroup analyses from the Phase 2a HERALD study. These data continue to demonstrate the best-in-class potential of ALG-055009 across the cardio-metabolic space.”

Two presentations highlight the continued potent antiviral activity of ALG-000184 for chronic hepatitis B virus (HBV) infection in both untreated HBeAg⁺ and HBeAg^- subjects, demonstrating the potential for the molecule to become first-line therapy for chronic suppression and the backbone for regimens aimed at functional cure.

In HBeAg⁺ subjects with a very high mean HBV DNA level of 8.0 log₁₀ IU/mL at baseline, all experienced profound and persistent HBV DNA reductions after receiving an oral daily dose of 300 mg ALG-000184 monotherapy. At Week 48, 6 of 10 subjects (60%) achieved HBV DNA < LLOQ (10 IU/mL, target detected or target not detected). With treatment extension, this rate increased to 9 of 9 subjects (100%) at Week 96. Additionally, HBV DNA level continuously declined to < LLOQ (target not detected, <4.29 IU/mL) in 5 of 9 subjects at Week 96.

In HBeAg^- subjects, all 11 (100%) had rapid decline in HBV DNA levels and achieved sustained HBV DNA suppression (HBV DNA < LLOQ, target detected or target not detected) by Week 24. The HBV DNA suppression level was maintained in the ALG-000184 monotherapy cohort for up to 96 weeks, with further decline in HBV DNA to < LLOQ, target not detected, observed in all subjects (8/8) at Week 96.

Importantly, no viral breakthrough was observed in any chronic HBV infection subjects receiving ALG-000184 monotherapy for up to 96 weeks. The resistant analysis reported no known CAM resistant mutations had been identified with ALG-000184 monotherapy.   

HBV RNA level achieved < LLOQ (10 copies/mL) in all HBeAg⁺ and HBeAg^- subjects by Week 52 and Week 8, respectively. Furthermore, concurrent multi-log₁₀ reductions in HBV antigens (HBsAg, HBeAg, and HBcrAg) in HBeAg⁺ subjects and HBcrAg decline in HBeAg^- subjects were observed, suggesting the potential inhibition of cccDNA establishment by CAM-E 2^nd mechanism of action of ALG-000184.

A favorable tolerability profile has been demonstrated in untreated HBeAg⁺ and HBeAg^- subjects receiving 300 mg ALG-000184 for up to 96 weeks.

Additionally, two presentations will showcase the best-in-class potential of ALG-055009, a purpose built THR-β agonist discovered by Aligos scientists. As previously presented at AASLD’s The Liver Meeting in 2024, 12-weeks of once daily ALG-055009 treatment in MASH patients met the primary endpoint, with robust reductions in liver fat content at Week 12. Doses of 0.5 mg to 0.9 mg ALG-055009 demonstrated statistically significant reductions in liver fat at Week 12, with placebo-adjusted median relative reductions up to 46.2% as measured by MRI-PDFF. Eighteen subjects who were on stable GLP-1 agonist therapy qualified for enrollment in the study, with liver fat content meeting the inclusion criteria of ≥10% at baseline as measured by MRI-PDFF. Notably, 11/14 subjects on stable GLP-1 agonists treated with ALG-055009 had liver fat decreases, whereas 4/4 subjects on stable GLP-1 agonists treated with placebo had increases in liver fat over the 12-week dosing period. Treatment with ALG-055009 was well-tolerated, with rates of gastrointestinal-related AEs similar to placebo.

New data being presented at the EASL congress will demonstrate substantial, dose-dependent reductions in liver fat were observed across all key subgroups with 12 weeks of once daily ALG-055009 treatment. In addition, statistically significant improvements in atherogenic lipids were achieved with 12 weeks of ALG-055009 treatment. Reductions in lipids/lipoproteins were observed even in the context of stable GLP-1 agonist or statin use. This data suggests an added benefit of ALG-055009 for patients at risk for cardiovascular disease in addition to the previously reported liver fat lowering properties in a MASLD/MASH population.

Details of the presentations are as follows:

ALG-000184: Potential first-/best-in-class small molecule CAM-E for chronic hepatitis B virus (HBV) infection

Poster #: THU-261
Title: Monotherapy with the Novel Capsid Assembly Modulator ALG-000184 for up to 96 Weeks Results in Profound and Sustained HBV DNA Suppression in Untreated Subjects with Chronic HBV Infection
Presenter: Professor Man-Fung Yuen, MBBS, MD, PhD, DSc, Chair and Chief of the Division of Gastroenterology and Hepatology, University of Hong Kong
Date/Time: May 8, 2025 at 4:15pm – 5:00pm CET; May 8, 2025 at 8:30am – 5:00pm CET
Session: Poster Tour; Poster - Viral Hepatitis B and D: New therapies, unapproved therapies or strategies

Poster #: THU-256
Title: The Safety and Antiviral Effect of Oral Daily 300 mg ALG-000184 in Combination with Entecavir for up to 96 Weeks in Untreated HBeAg-Positive Subjects with Chronic Hepatitis B Virus Infection
Presenter: Professor Jinlin Hou, MD, Chairman and Professor of the Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University
Date/Time: May 8, 2025 at 8:30am – 5:00pm CET
Session: Poster - Viral Hepatitis B and D: New therapies, unapproved therapies or strategies

Poster #: THU-242
Title: Viral kinetics and sequence analysis of a phase I monotherapy study in subjects with chronic hepatitis B reveals a high barrier of resistance to the capsid assembly modulator ALG-000184
Presenter: Andreas Jekle, PhD
Date/Time: May 8, 2025 at 8:30am – 5:00pm CET
Session: Poster - Viral Hepatitis B and D: New therapies, unapproved therapies or strategies

ALG-055009: Potential best-in-class small molecule THR-β for Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Poster #: SAT-451
Title: ALG-055009, a novel thyroid hormone receptor beta agonist, demonstrated significant reductions in atherogenic lipids/lipoproteins, including lipoprotein (a), in patients with presumed metabolic dysfunction-associated steatohepatitis in the Phase 2a HERALD
Presenter: Stanley Wang, MD, PhD
Date/Time: May 8, 2025 at 9:45am – 10:30am CET; May 10, 2025 at 8:30am – 4:00pm CET
Sessions: Poster tour; Poster - MASLD: Therapy

Poster #: SAT-450
Title: ALG-055009, a novel thyroid hormone receptor beta (THR-beta) agonist, demonstrated robust reductions in liver fat at Week 12 across subgroups including glucagon-like peptide-1 (GLP-1) receptor agonist users in non-cirrhotic MASH patients in the Phase 2a HERALD study
Presenter: Megan Fitzgerald, PhD
Date/Time: May 10, 2025 at 8:30am – 4:00pm CET
Session: Poster - MASLD: Therapy

Poster #: SAT-430
Title: Population pharmacokinetic/pharmacodynamic modelling of novel thyroid hormone receptor beta agonist ALG-055009 reveals statistically significant correlation between exposure and key efficacy endpoints
Presenter: Kha Le, PhD
Date/Time: May 10, 2025 at 8:30am – 4:00pm CET
Session: Poster - MASLD: Therapy

Poster #: FRI-450
Title: ALG-055009, a potent and selective thyroid hormone receptor beta agonist for the treatment of metabolic dysfunction-associated steatohepatitis, induces pro-metabolic and anti-fibrotic gene expression in the liver of diet-induced obese mice
Presenter: Xuan Luong, PhD
Date/Time: May 9, 2025 at 8:30am – 5:00pm CET
Session: Poster - MASLD: Experimental and pathophysiology

Preclinical

Poster #: FRI-257
Title: Next generation hepatitis B virus antisense oligonucleotides incorporating novel chemistries demonstrated significantly improved properties compared to current clinical candidates
Presenter: Jin Hong, PhD
Date/Time: May 9, 2025 at 8:30am – 5:00pm CET
Session: Poster - Viral Hepatitis: Experimental and pathophysiology

About Aligos

Aligos Therapeutics, Inc. (NASDAQ: ALGS) is a clinical stage biotechnology company founded with the mission to improve patient outcomes by developing best-in-class therapies for the treatment of liver and viral diseases. Aligos applies its science driven approach and deep R&D expertise to advance its purpose-built pipeline of therapeutics for high unmet medical needs such as chronic hepatitis B virus infection, metabolic dysfunction-associated steatohepatitis (MASH), and coronaviruses.

For more information, please visit www.aligos.com or follow us on LinkedIn or X.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release that are not historical facts may be considered “forward-looking statements,” including without limitation, statements regarding Aligos’ financial results and performance as well as research and development activities, including regulatory status and the timing of announcements and updates relating to our regulatory filings and clinical trials. Such forward looking statements are subject to substantial risks and uncertainties that could cause our development programs, future results, performance, or achievements to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties inherent in the drug development process, including Aligos’ clinical-stage of development, the process of designing and conducting clinical trials, the regulatory approval processes, and other matters that could affect the sufficiency of Aligos’ capital resources to fund operations. For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Aligos in general, see Aligos’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 6, 2025 and its future periodic reports to be filed or submitted with the Securities and Exchange Commission. Except as required by law, Aligos undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances, or to reflect the occurrence of unanticipated events.  

Investor Contact
Aligos Therapeutics, Inc.
Jordyn Tarazi
Vice President, Investor Relations & Corporate Communications
+1 (650) 910-0427
jtarazi@aligos.com

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Inizio Evoke
Jake Robison
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FAQ

What were the key results from Aligos Therapeutics' ALG-000184 96-week trial for HBV?

ALG-000184 achieved 100% HBV DNA viral suppression in both HBeAg+ and HBeAg- subjects by Week 96, with no viral breakthrough observed and a favorable tolerability profile.

How effective was ALGS's ALG-055009 in treating MASH patients?

ALG-055009 demonstrated up to 46.2% placebo-adjusted median relative reductions in liver fat at Week 12, with significant improvements even in patients on GLP-1 agonists.

What was the safety profile of Aligos Therapeutics' ALG-000184 and ALG-055009?

Both drugs showed favorable tolerability profiles, with ALG-055009 showing gastrointestinal-related adverse events similar to placebo, and ALG-000184 being well-tolerated for up to 96 weeks.

How did ALG-055009 perform in patients already on GLP-1 agonists?

11 out of 14 subjects on stable GLP-1 agonists treated with ALG-055009 showed liver fat decreases, while all 4 subjects on GLP-1 agonists with placebo showed increases.

What were the HBV DNA suppression rates for ALG-000184 in different patient groups?

In HBeAg+ subjects, 9/9 achieved suppression by Week 96, while all HBeAg- subjects (11/11) showed rapid decline and sustained suppression by Week 24.