Aligos Therapeutics announces positive data on chronic hepatitis B and MASH treatments at AASLD 2024

Aligos Therapeutics, Inc. a clinical stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in liver and viral diseases, today announced positive data from one late-breaker oral and three poster presentations at the American Association for the Study of Liver Disease’s (AASLD) The Liver Meeting (TLM) 2024, being held November 15 – 19, 2024 in San Diego, CA.

The clinical poster presentation highlighted the continued potent antiviral activity of ALG-000184 for chronic hepatitis B (CHB) virus infection in both HBeAg-positive and HBeAg-negative subjects, demonstrating the potential for the molecule to become first-line therapy for chronic suppression and the backbone for regimens aimed at functional cure.

Data from ≤84 weeks following an oral daily dose of 300 mg ALG-000184 monotherapy demonstrated sustained HBV DNA suppression (<LLOQ <10 IU/mL) in 7/7 (100%) HBeAg-positive CHB subjects. All HBeAg- subjects achieved sustained HBV DNA suppression by Week 24 and 11/11 (100%) subjects achieved sustained HBV DNA <LLOQ at Week 48 with 10/11 (91%) subjects further achieving HBV DNA below the lower limit of detection (LLOD <4.92 IU/mL). Importantly, no subject demonstrated viral resistance to ALG-000184 monotherapy and suppression was maintained throughout the dosing period.

All subjects achieved sustained HBV RNA < LLOQ by Week 44 in HBeAg+ subjects and Week 8 in HBeAg- subjects. Multi-log₁₀ reductions in HBsAg, HBeAg, and HBcrAg were observed in HBeAg+ subjects, and HBcrAg decline was observed in HBeAg- subjects. In both patient populations, ALG-000184 continues to be well tolerated with no viral breakthrough observed and no known CAM resistant mutations identified with monotherapy treatment.

Additionally, the late-breaker oral presentation highlighted the best-in-class potential of ALG-055009, a purpose built THR-β agonist discovered by Aligos scientists. 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. Up to 70% of subjects achieved ≥30% relative reduction in liver fat compared to baseline, a positive prognostic indicator of histological improvements in MASH resolution and fibrosis reduction. 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.

Significant reductions in atherogenic lipids, including LDL-C, lipoprotein (a) and apolipoprotein B and dose-dependent increases in SHBG were observed. In particular, ALG-055009 demonstrated a dose-dependent reduction from baseline of up to 26.8% at Week 12 for lipoprotein (a), which is an established risk factor for cardiovascular disease that has been resistant to treatment with statin therapy. Treatment with ALG-055009 was well-tolerated, with rates of gastrointestinal-related AEs similar to placebo.

“The presentation of longer duration dosing of ALG-000184 in CHB patients strengthens our belief that this therapy will become both first-line for chronic suppression as well as the backbone of next generation HBV treatments aimed at functional cure,” stated Lawrence Blatt, PhD, MBA, Chairman, President, & CEO of Aligos Therapeutics. “Additionally, we are pleased to have presented the HERALD data, showing robust reductions in liver fat for patients treated with ALG-055009. The subgroup analysis in patients enrolled in the study on stable GLP-1 agonist therapy suggests a role for ALG-055009 to augment liver fat reductions in patients receiving incretin therapy.”

 

Details of the presentations are as follows:

 

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

Abstract #: 1213

Title: Monotherapy with the Capsid Assembly Modulator, ALG-000184, Results in High Viral Suppression Rates in Untreated HBeAg+ and HBeAg- Subjects with Chronic Hepatitis B Virus 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: November 15, 2024, 8:00am – 5:00pm PT

Abstract #: 1266

Title: Capsid Assembly Modulators Such as ALG-001075 Induce Profound HBV DNA Knockdown and Directly Target HBeAg In Vitro

Presenter: Cheng Liu, PhD

Date/Time: November 15, 2024, 8:00am – 5:00pm PT

 

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

Format: Oral presentation

Title: ALG-055009, a Novel Thyroid Hormone Receptor Beta (THR-β) Agonist, was Well-tolerated with Significant Reductions in Liver Fat at Week 12 in Non-cirrhotic MASH Patients in the Ongoing Randomized, Double-Blind, Placebo-controlled Phase 2

Presenter: Rohit Loomba, MD, MHSc, Chief, Division of Gastroenterology and Hepatology, University of California, San Diego

Date/Time: November 19, 2024 at 10:30am – 10:40am PT

Abstract #: 3226

Title: Nonclinical Toxicology Profile of ALG-055009, a Novel and Potent Thyroid Hormone Receptor β Agonist, for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Presenter: Dinah Misner, PhD

Date/Time: November 17, 2024, 8:00am – 5:00pm PT