Aligos Therapeutics, Inc. · NASDAQ:ALGS
Aligos Therapeutics — Technical Presentation (November 2024)
19 slides from Aligos Therapeutics's technical presentation, Nov 1, 2024
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: Disclosures
Disclosures I disclose the following financial relationship(s) with a commercial interest: • Scientific advisor or consultant for: Eli Lilly & Co., 89bio, Aardvark, Aligos, Altimmune, Alnlyam/Regeneron, Amgen, Arrowhead, AstraZeneca, Bristol Myers Squibb, CohBar, Galmed, Gilead, Glympse Bio, Hightid
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 was Well Tolerated in Phase 1, with Favorable Pharmacokinetics and Pharmacodynamics
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 with ALG-055009
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 would like to give a special thanks to Dr. Stephen Harrison who played a pivotal role in the design of the HERALD study 19
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