Aligos Therapeutics, Inc. · NASDAQ:ALGS

Aligos Therapeutics — Investor Presentation (March 2024)

35 slides from Aligos Therapeutics's investor presentation, March 2024

  1. Slide 1: Corporate Presentation March 2024

    Corporate Presentation March 2024

  2. Slide 2: Disclosures

    Disclosures This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and f

  3. Slide 3: Investment Thesis

    Aligos Investment Thesis • The Aligos team has decades of drug development experience in medicinal chemistry and liver/viral diseases • ALG-055009 for Metabolic Dysfunction-Associated Steatohepatitis (MASH) – Thyroid hormone receptor β (THR-β) is a clinically validated mechanism (MDGL) – ALG-055009

  4. Slide 4: Aligos Development Portfolio

    Aligos Development Portfolio Multiple Milestones Anticipated in 2024 Candidate Indication MOA 2024 Clinical Trial Timelines and Data Readouts Q1 2024 Q2 2024 Q3 2024 Q4 2024 THR-β Phase 2a ALG-055009 Topline data Agonist (12 week MRI-PDFF in MASH) MASH Oligonucleotide Undisclosed Preclinical Activit

  5. Slide 5: MASH

    MASH • Epidemiology, Pathogenesis • Competitive Landscape 4

  6. Slide 6: MASLD/MASH: A Global Disease with Limited Treatment Options

    MASLD/ MASH A Global Disease with Limited Treatment Options • 1.66B people worldwide living with MASLD/MASH; the highest prevalence in East Asia/Asia Pacific and South Asia • Global prevalence is 30% and a leading cause of liver-related morbidity including cirrhosis, hepatocellular carcinoma, liver

  7. Slide 7: MASH Pathogenesis

    MASH Pathogenesis Fatty acids = primary source of excess energy supply (from de novo lipogenesis & lipolysis) Lipotoxic Species Liver Injury Endoplasmic reticulum stress Mitochondrial dysfunction Pro-inflammatory cytokines release Apoptosis MASH biology is complex with multiple therapeutic approache

  8. Slide 8: THR-β is a Differentiated Mechanism in Late-Stage Clinical Development

    THR-β is a Differentiated Mechanism in Late-Stage Clinical Development GLP-1 FGF21 PPAR FASN THR-β Pros Pros Pros Pros Pros • Demonstrated clinical • Demonstrated clinical • Demonstrated clinical • Demonstrated clinical • Demonstrated clinical success in MASH success in MASH success in MASH success

  9. Slide 9: MASLD/MASH Potential Future Treatment Paradigm

    MASLD/MASH Potential Future Treatment Paradigm MASH (F4) ~1M patients* Injection Liver Targeted Therapies MASH (F3) Oral That Treat Fibrosis Required (e.g., THR-β, FGF-21, PPAR) ~2M patients* MASH (F1-F2) ~10M patients* MASLD1/MASH (F0) GLP-1 Treatment May Be ~70M patients* Sufficient *Estimated US

  10. Slide 10: Role of Hepatic Thyroid Dysfunction in MASLD/MASH Pathogenesis

    Role of Hepatic Thyroid Dysfunction in MASLD/MASH Pathogenesis Healthy Liver Steatotic Liver IMPAIRED Lipid Metabolism NORMAL Lipid Metabolism & Fatty Acid Oxidation T4 T4 & Fatty Acid Oxidation -β (No lipotoxicity) R TH Lipotoxicity β R- TH T3 (active) Reverse T3 Fibrosis T3 (active) (inactive) Rev

  11. Slide 11: ALG-055009: Small molecule THR-β agonist

    ALG-055009: Small molecule THR-β agonist 10

  12. Slide 12: ALG-055009: A Potential Best-in-Class THR-β Agonist for MASH

    ALG-055009 A Potential Best-in-Class THR-β Agonist for MASH • Discovered by Aligos; issued US patent expires 2040 • Purpose-built with enhanced pharmacologic properties – 5-50x fold more potent vs. competitor THR-β agonists – More β selective – Optimized for PK • Phase 1 highlights – PK - dose propo

  13. Slide 13: Enhanced Potency, PK Correlated with Efficacy

    Enhanced Potency, PK Correlated with Efficacy MRI PDFF* Resmetirom TERNS-501 VK-2809 ASC41^ ALG-055009 Relative Fat Reduction (median) PK - half life (t1/2) 2370 1750 267 267 50 THR-β Potency1 (EC50 cell-based assay, nM) Short half life, Long half life, less variable PK PK highly variable PK 36% 45%

  14. Slide 14: Resmetirom Data: MRI-PDFF and Liver Biopsy Correlation

    Resmetirom Phase 3 Data MRI-PDFF and Liver Biopsy Correlation Biopsy Response (%) Fibrosis Improvement (Placebo) MASH Resolution (Placebo) Change from Baseline PDFF at Week 52 (%) THR-β induced MRI-PDFF de-fatting strongly correlated with histologic improvement NR = Non-Responder. Image adapted from

  15. Slide 15: ALG-055009 Phase 1 Study Design

    ALG-055009 Phase 1 Study Design Part 1: Single Ascending Dose (SAD) Part 2: Multiple Ascending Dose (MAD) – Dosing PO QD X 14 days Part 3: Relative Bioavailability, Food Effect (Gel Cap) N = up to 64 Healthy Volunteers N = up to 80 Subjects with Hyperlipidemia N = 8 per Cohort, N = 6 ALG-055009 and

  16. Slide 16: Phase 1 Highlights: Doses Well Tolerated with Favorable PK

    Study ALG-055009-301 Phase 1 Highlights: Doses Well Tolerated with Favorable PK Single Ascending Dose - PK, Safety, Biomarkers • Oral doses evaluated: 0.1, 0.3, 0.9, 2.6, 4.0 mg • PK: dose proportional, with low variability – t1/2 = 20-24 hours (supports once daily (QD) dosing) • Safety: well tolera

  17. Slide 17: Multiple Ascending Dose - Biomarkers

    Multiple Ascending Dose - Biomarkers Part 2: Expected Thyromimetic Effects Observed Dosing Period Generally dose proportional decreases in lipids Generally dose proportional increases in SHBG (e.g., LDL, Apo-B, Triglycerides) Charfi et al., EASL 2022. clinicaltrials.gov; NCT05090111. 16

  18. Slide 18: Preliminary Phase 2a HERALD Study Design

    ALG-055009 Preliminary Phase 2a HERALD Study Design Dose #1 (low) ALG-055009 (N~20) Dose #2 ALG-055009 (N~20) Randomize Dose #3 ALG-055009 (N~20) Dose #4 (high) ALG-055009 (N~20) Placebo (N~20) Day 1 Week 12 Week 16 Treatment Period Follow-up Period (PO QD x 12 weeks) (4 weeks) • Population: 100 adu

  19. Slide 19: ALG-055009: A Potential Best-in-Class THR-β Agonist for MASH

    ALG-055009 A Potential Best-in-Class THR-β Agonist for MASH • Discovered by Aligos; issued US patent expires 2040 • Purpose-built with enhanced pharmacologic properties – 5-50x fold more potent vs. competitor THR-β agonists – More β selective – Optimized for PK • Phase 1 highlights – PK - dose propo

  20. Slide 20: Chronic Hepatitis B

    Chronic Hepatitis B • ALG-000184: Small molecule CAM-E 19

  21. Slide 21: CHB: High Unmet Need for Better Treatment Options

    CHB High Unmet Need for Better Treatment Options • 296M people worldwide living with CHB with 1.5M new infections each year • 820k deaths per year, mostly from cirrhosis and hepatocellular carcinoma • Primary cause of liver cancer worldwide 14M – Europe 116M - China & 5M – Americas1 Western Pacific

  22. Slide 22: The Dual Role of Capsid Assembly Modulators (CAMs)

    Hepatitis B Virus (HBV) Treatment The Dual Role of Capsid Assembly Modulators (CAMs) • In preclinical studies, 2 mechanisms of action (MoA): – Primary mechanism › Promotes the premature assembly of core protein, leading to the formation of empty capsids › Responsible for the deep reductions of HBV D

  23. Slide 23: ALG-000184: A Potential Best-in-Class CAM-E for CHB

    ALG-000184 A Potential Best-in-Class CAM-E for CHB • Initial IP licensed from the lab of Dr. Raymond Schinazi at Emory University; issued US patent expires in 2040 • Enhanced pharmacology – Picomolar potent – Enhanced absorption, liver targeting • Phase 1 highlights (≤300 mg ALG-000184 ± ETV x £48 w

  24. Slide 24: ALG-000184: Superior Potency and Activity vs. Competitor CAM-Es

    ALG-000184 Superior Potency and Activity vs. Competitor CAM-Es Parameter JNJ-63793,4 EDP-5145 AB-8366 ABI-43341,2 ALG-000184 Potency (cell culture HBV DNA 54 17 10 1.2 0.63 reduction, EC50 nM) Dose 250mg 800mg 100mg 200mg 10mg Mean HBV DNA decline in clinic 2.7 3.4 3.1 NA 3.7 (Log10 IU/mL) % of subj

  25. Slide 25: ALG-000184-201 Phase 1 Study in HV and CHB Subjects

    ALG-000184-201 Phase 1 Study in HV and CHB Subjects Parts 1-3: Complete • Part 1 (SAD): single oral doses (40, 100, 250 and 500 mg) in HV • Part 2 (MAD): 7 QD oral doses (150 and 250 mg) in HV • Part 3: QD oral doses (10-300 mg) x 28 days in treatment naïve (TN)/currently not treated (CNT) CHB Multi

  26. Slide 26: Antiviral Activity Data in CHB Subjects

    ALG-000184-201 Antiviral Activity Data in CHB Subjects Mean (SEM) Serum HBV DNA* and HBV RNA** Levels Change from Baseline Through the End of Study HBV DNA HBV RNA HBeAg- CHB subjects: Similar HBV DNA reduction for 10, 50 and 100 mg (~3-4 log10 IU/mL) HBV DNA, HBV RNA <LLOQ in ≥75% and 100% of subje

  27. Slide 27: HBsAg Reductions Observed in 28-Day Monotherapy (HBeAg+)

    ALG-000184 HBsAg Reductions Observed in 28-Day Monotherapy (HBeAg+) Subject 1 (100 mg) Subject 2 (300 mg) Subject 3 (300 mg) Subject 4 (300 mg) Subject 5 (300 mg) 300 mg ALG-000184 x 28 days results in 0.2-0.8 log10 IU/mL HBsAg decline in 50% of subjects Best-in-class activity Longer duration cohort

  28. Slide 28: Long Term Dosing in CHB Subjects Cohort Designs

    ALG-000184-201 – Long Term Dosing in CHB Subjects Cohort Designs Randomize N=8 Follow-up 3 active:1 placebo ALG-000184 100 mg + ETV x 24 weeks (ETV only) x 8 weeks ALG-000184 + Follow-up Placebo + ETV Cohort 1 ETV (ETV only) x 12 weeks N=11 E+ x 12 weeks x 8 weeks China N=8 Randomize Follow-up 3 act

  29. Slide 29: Antiviral Effect in CHB Subjects

    Antiviral Effect in CHB Subjects HBV DNA Change from Baseline Mean Change Individual changes of ALG-000184 monotherapy Number of subjects at timepoint • 300 mg ALG-000184±ETV • - Showed greater HBV DNA reduction than ETV monotherapy • - Achieved similar DNA reductions • No viral breakthrough was obs

  30. Slide 30: Chronic Suppression: Well Defined, Validated Approval Pathway

    Chronic Suppression Well Defined, Validated Approval Pathway Pathway endorsed by FDA, EMEA, and China FDA (CDE). Definition: HBV DNA <LLOQ at Week 48 Pathway was used to get tenofovir alafenamide (TAF; Gilead) approved in all 3 regions HBV Guidance from: FDA 2022; EMEA 2006; China 2023. 29

  31. Slide 31: Antiviral Effect in CHB Subjects: HBV Antigen Change

    ALG-000184-201 - Antiviral Effect in CHB Subjects HBV Antigen Change from Baseline Treatment (300 mg ALG-000184 ± ETV x ≤96 weeks) Number of subjects at timepoint • Substantial HBsAg, HBeAg, and HBcrAg reductions seen with combo Max declines: 2.0, 2.1 and 2.5 log10, respectively Graph plots subjects

  32. Slide 32: Safety Overview

    Safety Overview Treatment Emergent Adverse Events Part 4 Cohort 2 Part 4 Cohort B 300 mg ALG-000184 +/- ETV (n=15) (n=10) Serious Adverse Events (SAEs) None Treatment emergent AEs (TEAEs) leading to study drug discontinuation None 2 3 Subjects with Grade ≥3 TEAEs ALT/AST↑ (n=2) ALT/AST↑ neutropenia↑

  33. Slide 33: ALG-000184: A Potential Best-in-Class CAM-E for CHB

    ALG-000184 A Potential Best-in-Class CAM-E for CHB • Initial IP licensed from the lab of Dr. Raymond Schinazi at Emory University; issued US patent expires in 2040 • Enhanced pharmacology – Picomolar potent – Enhanced absorption, liver targeting • Phase 1 highlights (≤300 mg ALG-000184 ± ETV x £48 w

  34. Slide 34: Our Focused Approach Will Drive Value

    Our Focused Approach Will Drive Value ALG-055009 for MASH • First 2a HERALD patient dosed anticipated in Q2 2024 • Phase 2a HERALD topline safety and MRI-PDFF data expected Q4 2024 ALG-000184 for CHB • Phase 1b study is ongoing with interim data readouts expected at APASL, EASL, AASLD • Phase 2 enab

  35. Slide 35: Aligos Therapeutics

    ALIGOS THERAPEUTICS

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