ALG-055009 / Aligos Therap - LARVOL DELTA

ALG-055009 in non-cirrhotic adults with metabolic dysfunction-associated steatohepatitis (HERALD): a randomised, double-blind, placebo-controlled, phase 2a trial. (PubMed, Lancet Gastroenterol Hepatol) - P2 | "Statistically significant reductions in liver fat with ALG-055009 and no relevant safety issues suggest that ALG-055009 could offer a promising treatment approach for patients with MASH. Results support evaluating extended ALG-055009 dosing on liver histology in participants with MASH."

Journal • P2a data • Constipation • Fatigue • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Synergistic fat mass loss in diet-induced obese mice when thyroid hormone receptor-β agonist ALG-055009 was administered in combination with incretin receptor agonists (EASL 2026) - "In Phase I, mice were treated once daily with either vehicle, oral 1 mg/kg ALG-055009, subcutaneous incretin RAs, 10.0 nmol/kg semaglutide (SEMA), 3.0 nmol/kg tirzepatide (TIRZEP_lo), 10.0 nmol/kg tirzepatide (TIRZEP_hi), or combinations of ALG-055009 with incretin RAs for 4 weeks. In DIO mice, ALG-055009 in combination with incretin RAs resulted in profound, synergistic weight loss, with up to 39-40% decreases in BW within 4 weeks. Notably, the additional weight loss conferred by ALG- 055009 was from reduction in fat mass and not changes in lean mass. Initial evidence points to this synergistic response being due to increased energy expenditure via browning of WAT, a direct effect of THR-β activation."

Combination therapy • Preclinical • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

Co-Administration of Thyroid Hormone Receptor-beta Agonist ALG-055009 and Incretin Receptor Agonists Leads to Synergistic Weight Loss and Modulation of Molecular Pathways Underlying Adipocyte Dysfunction in Diet-Induced Obese Mice (ECO 2026) - "Introduction: ALG-055009 is a potent, selective thyroid hormone receptor (THR)-beta agonist that has demonstrated significant reductions in liver fat (placebo-adjusted median relative reductions up to 46.2%) and atherogenic lipids in clinical subjects with presumed metabolic dysfunction-associated steatohepatitis and stage 1-3 liver fibrosis...In Phase I, mice were treated once daily with either vehicle, oral 1 mg/ kg ALG-055009, subcutaneous incretin RAs, 10.0 nmol/kg semaglutide (SEMA), 3.0 nmol/kg tirzepatide (TIRZEP_lo), 10.0 nmol/kg tirzepatide (TIRZEP_hi), or combinations of ALG-055009 with incretin RAs for 4 weeks... In DIO mice, ALG-055009 in combination with incretin RAs resulted in profound, synergistic weight loss, with up to 39-40% decreases in BW within 4 weeks. Notably, the additional weight loss conferred by ALG-055009 was from reduction in fat mass and not changes in lean mass. Initial evidence points to this synergistic response being due to increased..."

Preclinical • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • FAM20C

ALG-055009: Potential best-in-class small molecule THR-β for obesity, MASH (GlobeNewswire) - "Additional nonclinical data demonstrating the potential synergies of ALG-055009 and incretin receptor agonists are expected to be presented at upcoming scientific conferences. Evaluation of a variety of options to fund continued development, including potential out-licensing, is ongoing."

Commercial • Preclinical • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

ALG-055009: Potential best-in-class small molecule THR-β for obesity… (GlobeNewswire) - "Recently presented in vivo data in diet induced obese (DIO) mice treated with semaglutide (SEMA), tirzepatide (TIRZEP), or a combination of ALG-055009 and SEMA or TIRZEP for 28 days demonstrated synergistic weight loss in the combination groups compared to monotherapy groups. SEMA monotherapy resulted in a maximum of 23.9 ±2.6% body weight loss, while the combination of SEMA and ALG-055009 had an additional 8.6% decrease for a maximum 33% body weight loss....Combination of TIRZEP (low) or TIRZEP (high) with ALG-055009 induced an additional 11.7% and 5.8% decrease for a maximum of 39% and 40% body weight loss respectively."

Preclinical • Obesity

ALG-055009: Potential best-in-class small molecule THR-β for obesity… (GlobeNewswire) - "Recently generated preclinical data combining ALG-055009 with incretin RAs in a diet-induced obese (DIO) mouse model exhibited profound synergistic effects in body weight loss when used in combination with semaglutide or tirzepatide. The combination therapy also demonstrated enhanced antihyperlipidemic effects as compared to monotherapy. These data are expected to be presented at a future scientific conference."

Preclinical • Obesity

A multipart phase 1 study of the safety, pharmacodynamics and pharmacokinetics of ALG-055009, a novel thyroid hormone receptor beta (THR-β) agonist for metabolic dysfunction-associated steatohepatitis (MASH), in healthy participants. (PubMed, Clin Pharmacol Drug Dev) - "Dose-dependent decreases in atherogenic lipids and increases in sex hormone binding globulin were observed. These results support further development of ALG-055009 for patients with MASH."

Journal • P1 data • PK/PD data • Dyslipidemia • Endocrine Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

ALG-055009-304: A Phase 1 Study in Healthy Volunteers to Evaluate the Relative Bioavailability of ALG-055009 Formulations (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Aligos Therapeutics | Recruiting ➔ Completed

Trial completion

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.'"