Aligos Therapeutics, Inc. · NASDAQ:ALGS
Aligos Therapeutics — Investor Presentation (May 2024)
40 slides from Aligos Therapeutics's investor presentation, May 2024
Slide 1: Corporate Presentation May 2024
Corporate Presentation May 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: 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
Slide 9: 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 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
Slide 11: ALG-055009: Small molecule THR-β agonist
ALG-055009: Small molecule THR-β agonist 10
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 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 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%
Slide 14: 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 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: 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 21: Chronic Hepatitis B
Chronic Hepatitis B • ALG-000184: Small molecule CAM-E 20
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 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 24: 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 25: HBV Treatment: The Dual Role of Capsid Assembly Modulators
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 26: 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 27: 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 2.7 3.4 3.1 NA 3.7 in clinic (log10 IU/mL) % of subj
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 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 29: ALG-000184-201 – Long Term Dosing in CHB Subjects
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
Slide 30: Antiviral Effect in CHB Subjects
Antiviral Effect in CHB Subjects HBV DNA Change from Baseline Number of subjects at timepoint • 300 mg ALG-000184±ETV • Showed greater HBV DNA reduction than ETV monotherapy • Achieved similar DNA reductions Yuen, M-F. et al., Oral Presentation 101807; APASL 2024. 29
Slide 31: 300 mg ALG-000184 Monotherapy (HBeAg+) Individual HBV DNA Over Time
300 mg ALG-000184 Monotherapy (HBeAg+) Individual HBV DNA Over Time No viral breakthrough during ALG-000184 monotherapy x ≤60 weeks 100% (10/10) of subjects achieved HBV DNA < 29 IU/mL 60% (6/10) of subjects achieved sustained HBV <10 IU/mL by week 48 Yuen, M-F. et al., Oral Presentation 101807; APA
Slide 32: 300 mg ALG-000184 + ETV vs. ETV Mean HBV RNA Over Time
300 mg ALG-000184 + ETV vs. ETV Mean HBV RNA Over Time 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 the combo regimen Up to Week 64, 100% of subjects experienced HB
Slide 33: ALG-000184: Chronic DNA Suppression versus Standard of Care
ALG-000184 Chronic DNA Suppression versus Standard of Care % Patients < LLOQ at Week 48 CHB (by HBV DNA Assay Sensitivity) HBeAg Drug Regulatory Pathway Status % < LLOQ % < LLOQ 29 IU/mL 10 IU/mL TDF (n=292)b 67% Presumably <21% E+ TAF (n=581)b 64% 300 mg ALG-000184 (n=10)c 10/10 (100%) 6/10 (60%) S
Slide 34: 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. 33
Slide 35: 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 • Secondary endpoints (clinically meaningful and/or corroborative) – HBeAg seroconversion in HBeAg+ CHB subj
Slide 36: ALG-000184-201 - Antiviral Effect in CHB Subjects
ALG-000184-201 - Antiviral Effect in CHB Subjects HBV Antigen Change from Baseline • Substantial HBsAg, HBeAg, and HBcrAg reductions seen with combo Max declines: 1.9, 2.2 and 2.6 log10, respectively Yuen, M-F. et al.,Oral Presentation 101807; APASL 2024. 35
Slide 37: Safety Overview
Safety Overview Treatment Emergent Adverse Events 300 mg ALG-000184 300 mg + ETV ALG-000184 N=15 N=10 Serious Adverse Event (SAE) 0 0 Treatment Emergent Adverse Event (TEAE) leading to study drug 0 0 discontinuation Grade ≥3 TEAE 4*,# 3# Concerning laboratory, ECG, vital sign, or physical examinatio
Slide 38: Antiviral Activity of HBV Drug Classes
Antiviral Activity of HBV Drug Classes Viral NAs siRNA* ASO** ALG-000184 Clinical Significance Marker (ETV, TDF, (CAM-E) TAF) DNA <LLOQ on treatment (chronic suppression) associated DNA ++ + + +++ with improved outcomes and is an approvable endpoint RNA + + +++ RNA levels correlate with HCC risk^ HB
Slide 39: 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 • Phase 1b study is ongoing
Slide 40: Aligos Therapeutics
ALIGOS THERAPEUTICS
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