ALG-055009 / Aligos Therap - LARVOL DELTA

A Phase 1 Study in Healthy Volunteers to Evaluate the Relative Bioavailability of ALG-055009 Formulations (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Aligos Therapeutics

New P1 trial

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 study (EASL 2025) - No abstract available

Clinical • P2a data • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

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 (EASL 2025) - P2 | "12 weeks of once daily ALG-055009 treatment in MASH subjects demonstrated significant reductions in liver fat, with efficacy observed across the baseline factors evaluated. This supports evaluation of longer durations of ALG-055009 and its effects on liver histology and indicates liver fat reductions with the next generation THR-beta agonist ALG-055009 may be observed across various baseline characteristics in the MASH patient population, including those associated with a worse prognosis."

Clinical • P2a data • Diabetes • Fibrosis • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

Population pharmacokinetic/pharmacodynamic modelling of novel thyroid hormone receptor beta agonist ALG-055009 reveals statistically significant correlation between exposure and key efficacy endpoints (EASL 2025) - "Population PK and exposure-response models were developed for ALG-055009. There was a statistically significant correlation between exposure and key efficacy endpoints of change from baseline in liver fat and proportion of responders of ≥30% relative liver fat reduction. These models will be used to provide guidance for dose selection for a Phase 2b study in patients with MASH."

Clinical • PK/PD data • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

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 study (EASL 2025) - "The statistically significant improvements in atherogenic lipids achieved with 12 weeks of ALG-055009 treatment may suggest an added benefit for patients at risk for CVD in addition to the previously reported liver fat lowering properties in a MASLD/MASH population. This data supports evaluation of longer duration ALG-055009 treatment in a dedicated clinical trial of patients with dyslipidemia (including those with MASLD/MASH) to better characterize the extent of reduction in atherogenic lipids/lipoproteins."

Clinical • P2a data • Cardiovascular • Diabetes • Dyslipidemia • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus • APOB

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 (EASL 2025) - "Preclinical and clinical data demonstrate that ALG-055009 is positioned as a potential best-in-class THRbeta agonist for the treatment of MASH. Here, we offer new evidence for the compound's mechanism of action. The resulting increased Fgf21 expression, another emerging therapeutic target for MASH, suggests improved lipid metabolism and insulin sensitivity from treatment with ALG-055009."

Preclinical • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • Oncology • Solid Tumor • ENPP2 • FGF21 • LGALS1

Aligos Therapeutics Announces Eight Abstracts Accepted for Presentation at the EASL Congress 2025 (GlobeNewswire) - "Aligos Therapeutics...announced eight abstracts have been accepted for poster presentations at the European Association for the Study of the Liver (EASL) Congress 2025, being held May 7 – 10, 2025 in Amsterdam, Netherlands."

Clinical data • Preclinical • Hepatitis B • Metabolic Dysfunction-Associated Steatohepatitis

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 Randomized, Double-Blind, Placebo-controlled Phase 2a HERALD Study (APASL 2025) - P2 | "12 weeks of once daily ALG-055009 treatment in MASH subjects met the primary endpoint, demonstrating significant reductions in liver fat and was well-tolerated, with rates of GI-related TEAEs similar to placebo. Additional liver fat reduction was observed among subjects with stable GLP-1 agonist use. This data supports evaluation of longer durations of ALG-055009 and its effects on liver histology."

Clinical • P2a data • CNS Disorders • Diabetes • Endocrine Disorders • Fibrosis • Gastrointestinal Disorder • Immunology • Insomnia • Metabolic Dysfunction-Associated Steatohepatitis • Sleep Disorder • Type 2 Diabetes Mellitus • APOB

Aligos Therapeutics Presents Positive Data at APASL 2025 (GlobeNewswire) - P2 | N=102 | HERALD (NCT06342947) | Sponsor: Aligos Therapeutics | "Additionally, the third oral presentation will highlight 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....2-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."

P2 data • Metabolic Dysfunction-Associated Steatohepatitis

ALG-055009 in Non-cirrhotic Adults With MASH (HERALD) (clinicaltrials.gov) - P2 | N=102 | Completed | Sponsor: Aligos Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Sep 2024 | Trial primary completion date: Nov 2024 ➔ Aug 2024

Trial completion • Trial completion date • Trial primary completion date • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

A Phase 1 Study to Evaluate the Drug-Drug Interaction Potential Between ALG-055009 and Statin Therapy(Ies) (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Aligos Therapeutics | Active, not recruiting ➔ Completed | N=27 ➔ 14

Enrollment change • Trial completion

Aligos Therapeutics Announces Acceptance of…Late-Breaker Oral Presentation of Data from the Phase 2a HERALD Study of ALG-055009 in MASH Subjects at The Liver Meeting (TLM) 2024 (GlobeNewswire) - "Aligos Therapeutics, Inc...today announced four abstracts have been accepted, including one late-breaker oral presentation 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 abstracts released today can be found on the AASLD website at https://www.aasld.org/the-liver-meeting. Late-breaker abstracts will be available on November 15, 2024."

P2a data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

NONCLINICAL TOXICOLOGY PROFILE OF ALG-055009, A NOVEL AND POTENT THYROID HORMONE RECEPTOR Β AGONIST, FOR THE TREATMENT OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS (MASH) (AASLD 2024) - "Recently, RezdiffraTM (resmetirom) was approved to treat MASH, demonstrating the utility of thyroid hormone receptor β (THRβ) agonists in MASH. ALG-055009 is a potent and selective THR-β agonist with favorable in vitro safety and ADME properties and repeat-dose toxicity profile in rats and dogs. ALG-055009 also dose-dependently reduced levels of atherogenic lipids. Combined, this profile indicates ALG-055009 has the potential to be a best-in-class THR-β agonist for the treatment of MASH."

Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Aligos Therapeutics Announces Positive Topline Results from the Phase 2a HERALD Study of ALG-055009 for the Treatment of MASH (GlobeNewswire) - P2a | N=100 | NCT06342947 | Sponsor: Aligos Therapeutics | "Aligos Therapeutics, Inc...today announced positive topline results from the Phase 2a HERALD study of ALG-055009, a thyroid hormone receptor beta (THR-β) agonist, in metabolic-dysfunction associated steatohepatitis (MASH) subjects....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....Treatment with ALG-055009 resulted in significant reductions in atherogenic lipids, including LDL-C, lipoprotein (a) (LpA), and apolipoprotein B (ApoB). In addition, dose dependent increases in sex hormone binding globulin (SHBG), a marker of THR-β target engagement in the liver, were observed."

P2a data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Discovery and Preclinical Profile of ALG-055009, a Potent and Selective Thyroid Hormone Receptor Beta (THR-β) Agonist for the Treatment of MASH. (PubMed, J Med Chem) - "The authors present the highly potent and selective compound ALG-055009 (14) as a potential best in class THR-β agonist. The high metabolic stability and good permeability translated well in vivo to afford a long in vivo half-life pharmacokinetic profile with limited liability for DDI, and it overcomes certain drawbacks seen in recent clinical candidates."

Journal • Preclinical • Dyslipidemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

ALG-055009 in Non-cirrhotic Adults With MASH (HERALD) (clinicaltrials.gov) - P2 | N=100 | Active, not recruiting | Sponsor: Aligos Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Aligos Therapeutics Announces the Completion of Enrollment in the ALG-055009 Phase 2a HERALD Study for the Treatment of MASH (Yahoo Finance) - "'We thank the patients, their families and our investigators for their efforts. In addition, I'd like to welcome Dr. Rohit Loomba as our Principal Investigator for the HERALD study. Dr. Loomba has a broad track record of contributions to the MASH field, having pioneered the use of MRI-PDFF as a noninvasive test to assess liver steatosis. We look forward to his insights and contributions to the HERALD study and beyond.'"

Aligos Therapeutics Announces the Completion of Enrollment in the ALG-055009 Phase 2a HERALD Study for the Treatment of MASH (GlobeNewswire) - "Aligos Therapeutics...announced that it has completed enrollment in the ALG-055009 Phase 2a HERALD study for metabolic dysfunction-associated steatohepatitis (MASH) with topline safety and efficacy data anticipated in early Q4 2024. The company also announced that Dr. Rohit Loomba will serve as Principal Investigator for the study.....HERALD (NCT06342947) is a randomized, double-blind, placebo-controlled trial that has enrolled approximately 100 subjects with presumed MASH and stage 1-3 liver fibrosis (F1-F3)."

Enrollment closed • P2a data • Metabolic Dysfunction-Associated Steatohepatitis

ALG-055009 in Non-cirrhotic Adults With MASH (HERALD) (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Aligos Therapeutics

New P2 trial • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Pharmacodynamics of multiple oral doses of ALG-055009, a THRβ agonist, in hyperlipidemic subjects (APASL 2024) - P1 | "Favorable, dose-dependent pharmacodynamic effects on atherogenic lipids and SHBG were observed with multiple dosing of ALG-055009 in HL subjects."

Clinical • PK/PD data • Dyslipidemia • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • APOB

Aligos Therapeutics Virtual KOL Event – Phase 2a HERALD Study of ALG-055009 in MASH (LifeSci Events) - "Join Aligos Therapeutics for a virtual KOL event featuring Stephen Harrison, MD...who will discuss the unmet need and current treatment landscape for patients with metabolic dysfunction-associated steatohepatitis (MASH, previously known as NASH). Dr. Harrison will also discuss the potentially differentiating features of ALG-055009, a next generation thyroid hormone beta agonist, and the Phase 2a HERALD study, which is evaluating the safety and efficacy of ALG-055009."

Live event

A Phase 1 Study to Evaluate the Drug-Drug Interaction Potential Between ALG-055009 and Statin Therapy(Ies) (clinicaltrials.gov) - P1 | N=27 | Active, not recruiting | Sponsor: Aligos Therapeutics

New P1 trial

NONCLINICAL EFFICACY, PHARMACOKINETIC/PHARMACODYNAMIC (PK/PD), AND TOXICOLOGY PROFILE OF ALG-055009, A NOVEL AND POTENT THYROID HORMONE RECEPTOR Β AGONIST, FOR THE TREATMENT OF NON-ALCOHOLIC STEATOHEPATITIS (NASH) (AASLD 2023) - "ALG-055009 is a potent and selective THR-β agonist with favorable in vitro safety and ADME properties and repeat-dose toxicity profile in rats and dogs. ALG-055009 also dose-dependently reduced levels of atherogenic lipids. Combined, this profile indicates ALG-055009 has the potential to be a best-in-class THR-β agonist for the treatment of NASH."

Clinical • PK/PD data • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Non-alcoholic Steatohepatitis • Obesity

A Study of ALG-055009 in Healthy Volunteers and Subjects With Hyperlipidemia (clinicaltrials.gov) - P1 | N=98 | Completed | Sponsor: Aligos Therapeutics | Active, not recruiting ➔ Completed | N=152 ➔ 98

Enrollment change • Trial completion • Dyslipidemia • Hepatology • Non-alcoholic Steatohepatitis

Aligos Therapeutics Announces IND Clearance for NASH lead, ALG-055009 (GlobeNewswire) - "Aligos Therapeutics, Inc...today announced it has received clearance of its Investigational New Drug (IND) application from the US Food and Drug Administration (FDA) for ALG-055009, it’s thyroid hormone receptor beta agonist (THR-β), intended for the treatment of nonalcoholic steatohepatitis (NASH)....'Equally important, we remain on track to submit the Phase 2a protocol to the IND in Q4 2023 and expect to initiate enrollment in Q1 2024. We look forward to sharing topline proof of concept data from the study in Q4 2024'....The study is designed to evaluate the safety and efficacy of up to 4 dose levels of ALG-055009, compared to placebo, over a 12-week treatment period in presumed NASH patients. As is typical for studies at this phase of development, the study’s primary endpoint will be change in MRI-PDFF, which has been shown to correlate with liver histology with other THR-β agonists in development."

Clinical protocol • IND • New P2a trial • P2a data • Metabolic Disorders • Non-alcoholic Steatohepatitis