Aligos Therapeutics, Inc. · NASDAQ:ALGS
Aligos Therapeutics — Investor Presentation (August 2024)
41 slides from Aligos Therapeutics's investor presentation, August 2024
Slide 1: Corporate Presentation
Corporate Presentation August 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 2024 Clinical Trial Timelines and Data Readouts Q1 2024 Q2 2024 Q3 2024 Q4 2024 THR-β Phase 2a Topline data ALG-055009 Agonist (12 week MRI-PDFF in MASH) MASH Oligonucleotide Undisclosed Preclinical Activit
Slide 5: MASH
MASH • Epidemiology, Pathogenesis • Competitive Landscape 4
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 MASH biology is complex with multiple therapeutic approache
Slide 8: MASLD/MASH Potential Future Treatment Paradigm
MASLD/MASH Potential Future Treatment Paradigm MASH (F4) ~1M patients Injection MASH (F3) Liver Targeted Therapies ~2M patients Oral That Treat Fibrosis Required (e.g., THR-β, FGF-21, PPAR) MASH (F2) ~3M patients MASH (F1) ~6M patients MASLD1/MASH (F0) GLP-1 Treatment May Be Sufficient ~71M patients
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 -β (No lipotoxicity) R TH Lipotoxicity β R- TH T3 (active) Reverse T3 Fibrosis T3 (active) (inactive) Rev
Slide 10: ALG-055009: Small molecule THR-β agonist
ALG-055009: Small molecule THR-β agonist 9
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 vs. competitor THR-β agonists – More β selective – Optimized for PK • Phase 1 highlights – PK - dose prop
Slide 12: 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%
Slide 13: Resmetirom Phase 3 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
Slide 14: The Continued Need in MASH
The Continued Need in MASH Translation of MRI-PDFF to Liver Biopsy MRI-PDFF & LIVER BIOPSY DATA BY MOA Relative Reduction in Liver Fat (12-Week MRI-PDFF) ≥1 Stage Fibrosis Improvement (Phase 2b)4 Placebo ≥1 Stage Fibrosis Improvement Placebo Adjusted Fibrosis Improvement 72% 70% 64% 60% 58% 57% 57%
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
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
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
Slide 18: ALG-055009 Phase 2a HERALD Study Design
ALG-055009 Phase 2a HERALD Study Design 0.3 mg ALG-055009 (N~20) 0.5 mg ALG-055009 (N~20) Randomize 0.7 mg ALG-055009 (N~20) 0.9 mg 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 adult subjects with MASH and li
Slide 19: HERALD Study Key Entry Criteria
HERALD Study Key Entry Criteria • Inclusion – 18-75 years old, BMI ≥25 kg/m2 – F1 – F3 MASH diagnosis based on, › Liver biopsy (within 6 months) – NAS ≥4 with a score of ≥1 in each category › Having ≥2 metabolic syndrome criteria and Fibroscan between 7-20 kPa – CAP >300 dB/m – MRI-PDFF ≥10% • Exclu
Slide 20: Chronic Hepatitis B
Chronic Hepatitis B • ALG-000184: Small molecule CAM-E 19
Slide 21: 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 22: Therapeutic Goals of HBV Antiviral Drugs
Therapeutic Goals of HBV Antiviral Drugs Current treatment options Nucleoside/Nucleotide Interferon alfa (IFNα) analogs (NAs): • Injectable • Oral • For use in functional • For use in chronic DNA cure suppression • HBsAg < LLOQ ~6 • HBV DNA <LLOQ after months after a finite 48 weeks on treatment tre
Slide 23: Rethinking CHB Treatment: A New Era
Rethinking CHB Treatment: A New Era The industry has learned from the issues of 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 date is great
Slide 24: 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
Slide 25: 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 20401 • Enhanced pharmacology – Picomolar potent – Enhanced absorption with high liver uptake • Phase 1 highlights (≤300 mg ALG-000184 ± ETV
Slide 26: 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
Slide 27: ALG-000184-201 – Long Term Dosing in CHB Subjects Part 4 Cohort Designs
ALG-000184-201 – Long Term Dosing in CHB Subjects Part 4 Cohort Designs N=8 Randomize Follow-up 3 active:1 placebo ALG-000184 300 mg + ETV x ≤96 weeks (ETV only) x 8 weeks China N=2 Follow-up Placebo + ETV Cohort 2 ALG-000184 300 mg + ETV x ≤96 weeks (ETV only) x 12 weeks N = 15 E+ x 8 weeks Cohort
Slide 28: Antiviral Effect in CHB Subjects (HBeAg+)
Antiviral Effect in CHB Subjects (HBeAg+) HBV DNA Change from Baseline ALG-000184 Add on Number of subjects at each timepoint • 300 mg ALG-000184±ETV • Showed greater HBV DNA reduction than ETV monotherapy Achieved similar DNA reductions +/-ETV Yuen, M-F. et al.,; EASL 2024. 27
Slide 29: 300 mg ALG-000184 Monotherapy (HBeAg+) Individual HBV DNA Decline
300 mg ALG-000184 Monotherapy (HBeAg+) Individual HBV DNA Decline 300 mg monotherapy £ 72 weeks No viral breakthrough during ALG-000184 monotherapy x ≤72 weeks 60% (6/10) of subjects achieved sustained HBV DNA <10 IU/mL by week 48 and 90% (9/10) by week 72 Yuen, M-F. et al.,; EASL 2024. 28
Slide 30: 300 mg ALG-000184 + ETV vs. ETV (HBeAg+) Mean HBV RNA Over Time
300 mg ALG-000184 + ETV vs. ETV (HBeAg+) Mean HBV RNA Over Time ALG-000184 Add on Number of subjects at each timepoint At Week 12, there was a >3 log10 copies/mL RNA decline with ALG-000184 ± ETV vs. no change with ETV After adding ALG-000184 on top of ETV at Week 12, the RNA decline was similar to
Slide 31: Antiviral Effect in CHB Subjects (HBeAg-)
Antiviral Effect in CHB Subjects (HBeAg-) HBV DNA Change from Baseline Number of subjects at each timepoint • 300 mg ALG-000184 showed rapid and sustained DNA reductions with no viral breakthrough Agarwal, K. et al. EASL 2024. 30
Slide 32: 300 mg ALG-000184 Monotherapy (HBeAg-) Individual HBV DNA Decline
300 mg ALG-000184 Monotherapy (HBeAg-) Individual HBV DNA Decline 100% (11/11) of subjects achieved HBV DNA < LLOQ (10 IU/mL) by Week 20 91% (10/11) of subjects achieved HBV DNA < LLOD (< 4.92 IU/mL) by Week 48 Agarwal, K. et al. EASL 2024. 31
Slide 33: 300 mg ALG-000184 Monotherapy (HBeAg-) Individual HBV RNA Decline
300 mg ALG-000184 Monotherapy (HBeAg-) Individual HBV RNA Decline 100% (11/11) of subjects achieved HBV RNA < LLOQ (10 copies/mL) by week 6 Agarwal, K. et al. EASL 2024. ^Liu et al., J Infect Dis, 2022. Mak et al., J Gastroenterology, 2021. Ding et al. Hepatology, 2021. 32
Slide 34: ALG-000184 Chronic DNA Suppression versus Standard of Care
ALG-000184 Chronic DNA Suppression versus 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% 28
Slide 35: 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 at Week 48 following treatment with investigational agent versus standard of care (nucleos(t)ide an
Slide 36: ALG-000184 Phase 2 Chronic Suppression Study Planned Efficacy Endpoints
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 infected subjects • Secondary endpoints (clinically meaningful and/or corroborative) – HBeAg seroconversion
Slide 37: ALG-000184-201 - Antiviral Effect in HBeAg+ CHB Subjects
ALG-000184-201 - Antiviral Effect in HBeAg+ CHB Subjects HBV Antigen Change from Baseline Number of subjects at each timepoint Continued substantial HBsAg, HBeAg, and HBcrAg reductions noted with combo through week 72 Mean max declines: 2.1, 2.6 and 2.7 log10 IU/mL, respectively Graph plots subjects
Slide 38: Mean HBeAg and Anti-HBe Antibody Level Over Time
300 mg ALG-000184 + ETV Mean HBeAg and Anti-HBe Antibody Level Over time Anti-HBe antibody (HBeAb) level showed positive trend with decline of HBeAg Yuen, M-F. et al.,; EASL 2024. 37
Slide 39: Safety Overview – 300 mg ALG-000184 ± ETV
Safety Overview – 300 mg ALG-000184 ± ETV Treatment Emergent Adverse Events HBeAg-Negative HBeAg-Positive Population 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 study None dru
Slide 40: Our Portfolio of Best-in-Class Drug Candidates Will Drive Value
Our Portfolio of Best-in-Class Drug Candidates Will Drive Value ALG-055009 for MASH üPhase 2a HERALD enrollment completed in May 2024 • Phase 2a HERALD topline safety and MRI-PDFF data expected in early Q4 2024 ALG-000184 for CHB üGreater DNA suppression observed vs. NAs üPhase 1b study is ongoing w
Slide 41: Aligos Therapeutics
ALIGOS THERAPEUTICS
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