Aligos Therapeutics, Inc. · NASDAQ:ALGS
Aligos Therapeutics — APASL 2025
19 slides from Aligos Therapeutics's conference presentation, March 2025
Slide 1: ALG-055009, a Novel THR-β Agonist, Well-tolerated with Significant Reductions in Liver Fat
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 Rohit Loomba1, Dimple Desai2, Daniel Santillano3, Kathryn
Slide 2: Disclosure of Conflict of Interest
Disclosure of Conflict of Interest I am currently employed with Aligos Therapeutics, Inc. 2
Slide 3: Role of Hepatic Thyroid Dysfunction in MASLD/MASH Pathogenesis
Role of Hepatic Thyroid Dysfunction in MASLD/MASH Pathogenesis Healthy Liver MASH Liver IMPAIRED Lipid Metabolism NORMAL Lipid Metabolism & Fatty Acid Oxidation T4 T4 & Fatty Acid Oxidation (No lipotoxicity) Lipotoxicity T3 (active) Reverse Fibrosis T3 T3 (active) Reverse T3 (inactive) (inactive) Di
Slide 4: ALG-055009 is a Highly Potent and Selective THR-β Agonist
ALG-055009 is a Highly Potent and Selective THR-β Agonist • Thyroid hormone receptor-beta (THR-β) is the primary THR expressed in the liver and plays an important role in lipid metabolism.1,2 • THR-β agonists reduce atherogenic lipids, decrease hepatic fat, and improve liver histology in MASH.3 • AL
Slide 5: ALG-055009 Well Tolerated in Phase 1, with Favorable PK and PD
ALG-055009 was Well Tolerated in Phase 1, with Favorable Pharmacokinetics and Pharmacodynamics ALG-055009 Multiple Dose PK • In Phase 1, single (up to 4.0 mg) and multiple (up to 1.0 mg QD for 14 days) doses of ALG-0550091: – Were well-tolerated – Had dose proportional PK and low variability – Demon
Slide 6: Phase 2a HERALD Study Design: Randomized, Double-Blind, Placebo-Controlled
ALG-055009 Phase 2a HERALD Study Design: Randomized, Double-Blind, Placebo-Controlled Key Entry Criteria: • 18-75 years old Placebo (N=22) >85kg body weight • BMI ≥25 kg/m2 ≤85kg body 0.3 mg ALG-055009 (N=20) • Presumed MASH weight Randomize • Non-cirrhotic (F1-F3) 0.5 mg ALG-055009 (N=22) • MRI-PDF
Slide 7: Baseline Characteristics Generally Balanced Across Arms
HERALD: Baseline Characteristics Generally Balanced Across Arms Consistent with Today’s At-Risk MASH Population ALG-055009 Placebo (N=22) 0.3 mg 0.5 mg 0.7 mg 0.9 mg* (N=20) (N=22) (N=20) (N=18, >85 kg) Age, mean (years) 48.5 53.3 49.5 51.4 48.1 Female, n (%) 21 (95.5) 12 (60.0) 8 (36.4) 14 (70.0) 8
Slide 8: Primary Endpoint Achieved
HERALD: Primary Endpoint Achieved Placebo-Adjusted Median Relative Change in Liver Fat at Week 12 Note: Data from MRI-PDFF analysis dataset, defined as all randomized subjects who have MRI-PDFF measurements available at both baseline and Week 12; median % change in placebo was +7.2%; *p<0.05 ***p<0.
Slide 9: Significant MRI-PDFF Response Rates
HERALD: Significant MRI-PDFF Response Rates at Week 12 Up to 70% of Patients Achieved ≥30% Relative Reduction in Liver Fat 1. Loomba et al. Hepatology (2021). **p<0.01 ***p<0.001. MRI-PDFF response of ≥30% relative reduction in liver fat is predictive of histologic improvements1 9
Slide 10: Additional Fat Reduction in Subjects with Stable Use of GLP-1 Agonists
Additional Fat Reduction in Subjects with Stable Use of GLP-1 Agonists Median Relative Percent Change in Liver Fat at Week 12 Note: Subjects on GLP-1 agonists (semaglutide (n=12), liraglutide (n=4) or dulaglutide(n=2)) at baseline were required to have stable use for ≥12 weeks prior to randomization
Slide 11: No Apparent Impact of Gender on Liver Fat Reduction
No Apparent Impact of Gender on Liver Fat Reduction with ALG-055009 Median Relative Percent Change in Liver Fat at Week 12 Note: Bolded dashed line indicates 30% relative reduction in liver fat. Substantial, dose-dependent liver fat reductions observed among both males and females 11
Slide 12: ALG-055009 Demonstrated Improvements in Lipid/Lipoproteins
ALG-055009 Demonstrated Improvements in Lipid/Lipoproteins Median Percent Change from Baseline at Week 12 LDL-C = low density lipoprotein cholesterol; LpA = lipoprotein (a); ApoB = apolipoprotein B; n: number of subjects with available data at week 12; N: number of subjects in MRI-PDFF analysis set;
Slide 13: Dose-dependent Increases in Sex Hormone Binding Globulin
HERALD: Dose-dependent Increases in Sex Hormone Binding Globulin Up to ~90% Increase from Baseline in Sex Hormone Binding Globulin (SHBG) SHBG is a marker of THR-β target engagement in the liver Significant (p<0.0001) increases compared to placebo observed 13
Slide 14: Favorable Safety and Tolerability Profile
HERALD: Favorable Safety and Tolerability Profile Rates of GI-related TEAEs Similar to Placebo • No SAEs in subjects receiving ALG-055009 – One unrelated SAE (hemangioma of bone) in a subject receiving placebo • One discontinuation due to a treatment emergent adverse event (TEAE) of worsening insomn
Slide 15: Favorable Safety and Tolerability Profile
HERALD: Favorable Safety and Tolerability Profile Rates of GI-related TEAEs Similar to Placebo ALG-055009 Placebo (N=22) 0.3mg 0.5mg 0.7mg 0.9mg n, (%) (N=20) (N=22) (N=20) (N=18) Any TEAE 17 (77.3) 14 (70.0) 11 (50.0) 14 (70.0) 11 (61.1) TEAE Leading to Study Drug 0 0 1a (4.5) 0 0 Discontinuation S
Slide 16: No Treatment Emergent Changes in Vital Signs Observed
HERALD: No Treatment Emergent Changes in Vital Signs Observed Heart Rate Body Temperature Diastolic Blood Pressure Systolic Blood Pressure 16
Slide 17: ALG-055009 has no Apparent Effect on QTcF Intervals
HERALD: ALG-055009 has no Apparent Effect on QTcF Intervals No trends for QTcF prolongation across dose levels No subject receiving ALG-055009 experienced a QTcF >500 ms and/or change from 17 baseline in QTcF of >60 ms
Slide 18: HERALD Phase 2a Study Conclusions
HERALD Phase 2a Study Conclusions • Primary endpoint achieved, with robust reductions in liver fat content at Week 12 – Up to 46% placebo-adjusted median relative reductions – Up to 70% of patients with ≥30% decrease in liver fat – 11/14 subjects on stable GLP-1 treated with ALG-055009 had liver fat
Slide 19: Acknowledgements
Acknowledgements We wish to thank the patients, and the investigators and their support staff who participated in this study. We wish to thank Dr. Ira Jacobson and Dr. Brent Tetri for their independent safety oversight of this study. We would like to give a special thanks to Dr. Stephen Harrison who