Aligos Therapeutics, Inc. · NASDAQ:ALGS
Aligos Therapeutics — Investor Presentation (October 2024)
43 slides from Aligos Therapeutics's investor presentation, October 2024
Slide 1: Corporate Presentation October 2024
CORPORATE PRESENTATION October 2024
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
Slide 3: Investment Thesis
Aligos Investment Thesis • Aligos has decades of drug development experience in medicinal chemistry and liver/viral diseases • ALG-055009 for Metabolic Dysfunction-Associated Steatohepatitis (MASH) – Thyroid hormone receptor beta (THR-β) is a clinically validated mechanism (MDGL) – ALG-055009 has en
Slide 4: Aligos Development Portfolio
Aligos Development Portfolio Multiple Milestones Anticipated in 2024 Candidate Indication MOA Discovery Nonclinical Phase 1 Phase 2 Phase 3 Partner ALG-055009 MASH THR-β Agonist CHB ALG-000184 Monotherapy CAM-E CHB CAM-E + PEGBING® + ETV ALG-000184 Combination1 (mipeginterferon alfa-2b) ALG-097558 C
Slide 5: MASH
MASH • Epidemiology, Pathogenesis • Competitive Landscape
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
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 Harrison, et al. Clin Gastro and Hep. 2023. MASH biology is
Slide 8: MASLD/MASH Potential Future Treatment Paradigm
MASLD/MASH Potential Future Treatment Paradigm MASH (F4) ~1M patients MASH (F3) ~2M patients Injection Liver Targeted Therapies That Treat Fibrosis Required (e.g., Oral THR-β, FGF-21) MASH (F2) ~3M patients MASH (F1) ~6M patients GLP-1 Treatment May Be MASLD1/MASH (F0) Sufficient ~71M patients Sourc
Slide 9: 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 (No lipotoxicity) Lipotoxicity T3 (active) Reverse Fibrosis T3 T3 (active) Reverse T3 (inactive) (inactiv
Slide 10: ALG-055009 Small molecule THR-β agonist
ALG-055009 Small molecule THR-β agonist
Slide 11: 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 20401 • Purpose-built with enhanced pharmacologic properties – ~5-50x fold more potent – More β selective – Optimized for PK vs. competitor THR-β agonists • Phase 1 highlights – PK - dose pro
Slide 12: Phase 1 Study: SAD, MAD, Relative BA
Study ALG-055009-301: SAD, MAD, Relative BA 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 1st Dose 14th Dose Plasma ALG-055009 Concentration (n
Slide 13: Phase 2a HERALD Study Design
ALG-055009 Phase 2a HERALD Study Design Placebo (N=22) >85kg body weight ≤85kg body 0.3 mg ALG-055009 (N=20) • Population: 102 adult subjects weight Randomize with MASH and liver fibrosis 0.5 mg ALG-055009 (N=22) (F1-F3) • Primary endpoint: Relative 0.7 mg ALG-055009 (N=20) change in liver fat conte
Slide 14: HERALD: 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 15: HERALD: Primary Endpoint Achieved
HERALD: Primary Endpoint Achieved Placebo-Adjusted Median Relative Change in Liver Fat at Week 12 Note: Only subjects weighing >85 kg were enrolled in the 0.9 mg dose group, no body weight restrictions were implemented in other dose groups. Data from MRI-PDFF analysis dataset, defined as all randomi
Slide 16: ALG-055009 Demonstrated Significant Improvements in Liver Fat
ALG-055009 Demonstrated Significant Improvements in Liver Fat Placebo-adjusted Median Relative Percent Change in Liver Fat at Week 12^ ALG-055009 resmetirom ^Includes publicly reported data from the placebo-controlled Phase 2 trial of Resmetirom in a similar patient population conducted with differe
Slide 17: HERALD: Significant MRI-PDFF Response Rates at Week 12
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. Only subjects weighing >85 kg were enrolled in the 0.9 mg dose group; no body weight restrictions were implemented in ot
Slide 18: 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 19: HERALD Topline Data: Favorable Tolerability Profile
HERALD Topline Data: Favorable Tolerability Profile • Generally well tolerated, with no dose reductions • No serious adverse events • One discontinuation due to a treatment emergent adverse event (TEAE) of worsening insomnia in a subject with pre-existing insomnia • Majority of the TEAEs (98%) were
Slide 20: HERALD Phase 2a Study Summary
HERALD Phase 2a Study ALG-055009 Continues to Demonstrate the Potential to be the Best-in-class THR-β Agonist • 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 live
Slide 21: Chronic Hepatitis B
CHRONIC HEPATITIS B ALG-000184: Small molecule CAM-E
Slide 22: CHB: High Unmet Medical Need
CHB High Unmet Medical Need • 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 • Market opportunity estimated at $6.2B by 20312; Gilead HBV sales of $1B in 202
Slide 23: Therapeutic Goals of HBV Antiviral Drugs
Therapeutic Goals of HBV Antiviral Drugs Current treatment options Nucleoside/Nucleotide analogs (NAs): Interferon alfa (IFNα) • Oral • Injectable • For use in chronic DNA suppression • For use in functional cure – HBV DNA <LLOQ after 48 weeks on treatment – HBsAg < LLOQ ~6 months after a finite • L
Slide 24: Rethinking CHB Treatment: A New Era
Rethinking CHB Treatment: A New Era The industry has learned from the issues associated with first-generation investigational mechanisms such as siRNA, ASO, NAPs, CAMs, immunomodulators, and therapeutic vaccines. Functional cure is a difficult pathway The DNA suppression observed with ALG-000184 to
Slide 25: ALG-000184 Small molecule CAM-E
ALG-000184 Small molecule CAM-E
Slide 26: MOA: ALG-000184 (CAM-E) vs. Nucleos(t)ide Analogs
MOA: ALG-000184 (CAM-E) vs. Nucleos(t)ide Analogs Suppressing the Entire HBV Lifecycle Key Attributes Nucleos(t)ide Blocks the conversion of pgRNA to rcDNA Analogs • Reduces viral secretion 1st MOA • Causes the formation of empty capsids — Reduces viral secretion (HBV DNA/RNA) 2nd MOA • Prevents cap
Slide 27: 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 1 • Enhanced pharmacology – Picomolar potent – Enhanced absorption with high liver uptake • Phase 1 highlights (≤300 mg ALG-000184 ± ETV
Slide 28: 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 HVs • Part 2 (MAD): 7 QD oral doses (150 and 250 mg) in HVs • Part 3: QD oral doses (10-300 mg) x 28 days in treatment naïve (TN)/currently not treated (CNT) CHB sub
Slide 29: ALG-000184-201 – Long Term Dosing in CHB Subjects
ALG-000184-201 – Long Term Dosing in CHB Subjects Part 4 Cohort Designs China Randomize ALG-000184 300 mg + ETV x ≤96 weeks Follow-up (ETV only) 4 active:1 placebo x 8 weeks Cohort 2 N = 15 E+ Placebo + ETV Follow-up (ETV only) x 12 weeks ALG-000184 300 mg + ETV x ≤96 weeks x 8 weeks ROW Cohort B AL
Slide 30: Antiviral Effect in CHB Subjects (HBeAg+): HBV DNA
Antiviral Effect in CHB Subjects (HBeAg+) Mean HBV DNA Change from Baseline Mean HBV DNA Change from Baseline (log10 IU/ml) ALG-000184 Add on Time (week) Number of subjects at each timepoint Aligos oral, The Science of HBV Cure Meeting 2024. 300 mg ALG-000184±ETV Showed greater HBV DNA reduction tha
Slide 31: 300mg ALG-000184 Monotherapy (HBeAg+): Individual HBV DNA Decline
300mg ALG-000184 Monotherapy (HBeAg+) Individual HBV DNA Decline HBV DNA (log10 IU/ml) 300 mg monotherapy 72 weeks HBV DNA Baseline (log10 IU/ml) Visit (week) Visit (week) Yuen, M-F. et al; EASL 2024. No viral breakthrough during ALG-000184 monotherapy x ≤72 weeks 60% (6/10) of subjects achieved H
Slide 32: Antiviral Effect in CHB Subjects (HBeAg+): HBV RNA
Antiviral Effect in CHB Subjects (HBeAg+) Mean HBV RNA Change from Baseline Mean HBV RNA Change from Baseline ALG-000184 Add on (log10 IU/ml) Time (week) 3 Number of subjects at each timepoint Aligos oral, The Science of HBV Cure Meeting 2024. At Week 12, there was a >3 log10 copies/mL RNA decline w
Slide 33: Antiviral Effect in CHB Subjects (HBeAg-): HBV DNA
Antiviral Effect in CHB Subjects (HBeAg-) Mean HBV DNA Change from Baseline Mean HBV DNA Change from Baseline (log10 IU/ml) Time (week) Number of subjects at each timepoint Data on file. 300 mg ALG-000184 showed rapid and sustained DNA reductions 33 with no viral breakthrough
Slide 34: 300mg ALG-000184 Monotherapy (HBeAg-): Individual HBV DNA Decline
300 mg ALG-000184 Monotherapy (HBeAg-) Individual HBV DNA Decline HBV DNA Baseline (log10 IU/ml) HBV DNA (log10 IU/ml) Visit (week) Visit (week) Agarwal, K. et al. EASL 2024. 100% (11/11) of subjects achieved HBV DNA < LLOQ (10 IU/mL) by Week 20 34 91% (10/11) of subjects achieved HBV DNA < LLOD (<
Slide 35: 300mg ALG-000184 Monotherapy (HBeAg-): Individual HBV RNA Decline
300 mg ALG-000184 Monotherapy (HBeAg-) Individual HBV RNA Decline HBV RNA (log10 copies/ml) HBV RNA Baseline (log 10 copies/ml) Visit (week) Agarwal, K. et al. EASL 2024. Visit (week) ^Liu et al., J Infect Dis, 2022. Mak et al., J Gastroenterology, 2021. Ding et al. Hepatology, 2021. 100% (11/11) of
Slide 36: Chronic DNA Suppression vs. Standard of Care
ALG-000184 Chronic DNA Suppression vs. Standard of Care % Patients < LLOQ at Week 48 % Patients < LLOQ at Week 96 CHB (by HBV DNA Assay Sensitivity) (by HBV DNA Assay Sensitivity) HBeAg Drug Status % < LLOQ % < LLOQ % < LLOQ % < LLOQ 29 IU/mL 10 IU/mL 29 IU/mL 10 IU/mL TDF (n=140)a 93% 17% 91% 31% E
Slide 37: Chronic Suppression: Well Defined, Validated Approval Pathway
Chronic Suppression Well Defined, Validated Approval Pathway • Regulatory pathway for chronic suppressive therapy endorsed by FDA, EMEA, and China FDA (CDE) • Primary endpoint: Subjects with HBV DNA <LLOQ (10 IU/mL) at Week 48 following treatment with investigational agent versus standard of care (n
Slide 38: ALG-000184 Phase 2 Chronic Suppression Study
ALG-000184 Phase 2 Chronic Suppression Study Planned Efficacy Endpoints Primary endpoint (approvable endpoint*) • Proportion of subjects with HBV DNA < 10 IU/mL at W48 for both HBeAg+/- CHB subjects Secondary endpoints (clinically meaningful and/or corroborative) • HBeAg seroconversion in HBeAg+ CHB
Slide 39: Antiviral Effect in HBeAg+ CHB Subjects: HBV Antigens
ALG-000184-201 - Antiviral Effect in HBeAg+ CHB Subjects Mean HBV Antigen Change from Baseline HBV Antigen Change from Baseline (log 10 ) Visit (week) Number of subjects at each timepoint Graph plots subjects initially randomized to ALG-000184 + ETV and were compliant (confirmed by PK). Yuen, M-F. e
Slide 40: Mean HBeAg and Anti-HBe Antibody Level Over Time
300 mg ALG-000184±ETV Mean HBeAg and Anti-HBe Antibody Level Over time Mean HBeAb level over time Mean HBeAb level over time (PEI U/mL)) (COI) Visit (week) Yuen, M-F. et al.,; EASL 2024. Anti-HBe antibody (HBeAb) level showed positive trend with decline of HBeAg 40
Slide 41: Safety Overview – 300 mg ALG-000184 ± ETV
Safety Overview – 300 mg ALG-000184 ± ETV Treatment Emergent Adverse Events HBeAg-Positive Population HBeAg-Negative Population ALG-000184 Regimen 300mg QD + ETV 300mg QD 300mg QD N of subjects N=15 N=10 N=11 Serious Adverse Events (SAEs) None Treatment emergent AEs (TEAEs) leading to None study dru
Slide 42: Our Portfolio of Potential Best-in-Class Drug Candidates Will Drive Value
Our Portfolio of Potential Best-in-Class Drug Candidates Will Drive Value ALG-055009 for MASH ✓ Positive Phase 2a HERALD topline safety and MRI-PDFF data readout ahead of schedule in Q3 2024 • Phase 2b enabling activities underway; expected completion middle of 2025 • Assessing potential Phase 2b cl
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