Aligos Therapeutics, Inc. · NASDAQ:ALGS
Aligos Therapeutics — Investor Presentation (February 2024)
44 slides from Aligos Therapeutics's investor presentation, February 2024
Slide 1: Corporate Presentation February 2024
Lawrence M. Blatt, Ph.D. Chairman, CEO & Co-Founder C Corporate Presentation February 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: Aligos Development Portfolio
Aligos Development Portfolio Multiple Milestones/Data Readouts Anticipated in 2024 Candidate Indication MOA 2024 Clinical Trial Timelines and Data Readouts Q1 2024 Q2 2024 Q3 2024 Q4 2024 Topline data THR-β Phase 2a ALG-055009 Agonist (12 week MRI-PDFF in MASH) MASH Oligonucleotide Undisclosed Precl
Slide 4: MASH
MASH • ALG-055009, small molecule THR-β agonist 3
Slide 5: 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) ~2M patients* MASH (F1-F2) ~10M patients* MASLD/MASH (F0) GLP-1 Treatment May Be ~70M patients* Sufficient *Estimated US Inciden
Slide 6: 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 7: Thyroid Hormone Receptor β (THR-β)
Thyroid Hormone Receptor β (THR-β) 6
Slide 8: Role of Hepatic Thyroid Dysfunction in NAFLD/MASH Pathogenesis
Role of Hepatic Thyroid Dysfunction in NAFLD/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 9: ALG-055009 Comparisons to Other THR-β Drug Candidates
ALG-055009 Comparisons to Other THR-β Drug Candidates Resmetirom, TERN-501, VK-2809 and ASC41 TERN-501 Parameter Resmetirom VK-2809 ASC41^ ALG-055009 (discontinued) β/α Selectivity 2.5 2.3 1.4 1.4 3.8 THR-β Potency 2370 1750 267 267 50 (EC50 HEK293T cell-based assay, nM) PK - half life
Slide 10: 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 11: ALG-055009 Phase 1 Clinical Data
ALG-055009 Phase 1 Clinical Data 10
Slide 12: 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 13: Part 1: Single Ascending Dose - PK, Safety, Biomarkers
Study ALG-055009-301 Part 1: 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 tolerated – No serious adverse events (SAEs), Grade ≥3 t
Slide 14: Part 2: Multiple Ascending Dose - PK, Safety
Study ALG-055009-301 Part 2: Multiple Ascending Dose - PK, Safety • Oral doses evaluated: 0.3, 0.5, 0.6, 0.75 and 1.0 mg QD x 14 days • PK: favorable profile (dose-proportional, low variability (≤30%), 2x accumulation) • Safety: well tolerated, no clinical evidence of hypo or hyperthyroidism – No SA
Slide 15: Multiple Ascending Dose - Biomarkers
Multiple Ascending Dose - Biomarkers Part 2: Expected Thyromimetic Effects Observed Dosing Period Generally dose proportional increases in SHBG Charfi et al., EASL 2022. clinicaltrials.gov; NCT05090111. 14
Slide 16: Multiple Ascending Dose - Biomarkers
Multiple Ascending Dose - Biomarkers Part 2: Expected Thyromimetic Effects Observed Day Dose responsive reductions in lipids (e.g., LDL, Apo-B, Triglycerides) Charfi et al., EASL 2022. clinicaltrials.gov; NCT05090111. 15
Slide 17: Formulation / Food Effect Part 3
Formulation / Food Effect Part 3: PK Data Comparison in Healthy Volunteers at 0.6 mg Dose = 0.6 mg Gel cap vs. liquid formulation: similar PK with low variability, no food effect Phase 2 formulation (gel cap) confirmed Charfi et al., AASLD 2023. clinicaltrials.gov; NCT05090111. 16
Slide 18: ALG-055009 Preliminary Phase 2a Study Design
ALG-055009 Preliminary Phase 2 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: Adults subjects
Slide 19: ALG-055009 Summary
ALG-055009 Summary • Discovered by Aligos – issued US patent expires 2040 • THR-β agonist with high potency (EC50 = 50 nM) and β selectivity (3.8-fold) • Phase 1 – Safety – well tolerated without clinical safety signals – PK – favorable profile (linear, low variability) that is differentiated vs. re
Slide 20: Chronic Hepatitis B
ALIGOS THERAPEUTICS Chronic Hepatitis B
Slide 21: 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 22: ALG-000184 Superior Potency vs. Competitor CAM-Es
ALG-000184 Superior Potency vs. Competitor CAM-Es HBV DNA reduction Compound Current Status Cell Type (EC50 nM) 0.63 HepG2.117 Aligos ALG-000184 Phase 1 0.53 HepG2.2.15 2nd Gen Assembly ABI-4334 Phase 1 1.2 AD38 Assembly ABI-H3733 Partnered, BeiGene 5 AD38 Enanta EDP-514 Phase 1 17 HepG2.115 Vebicor
Slide 23: ALG-000184-201 Phase 1 Study Design
ALG-000184-201 Phase 1 Study in HV (Parts 1& 2) and CHB Subjects (Parts 3-5) 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 no
Slide 24: Part 3 Antiviral Activity Data in CHB Subjects
ALG-000184-201 - Part 3 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%
Slide 25: ALG-000184 In Vivo Superior Activity vs. Competitor CAMs
ALG-000184 In Vivo Superior Activity vs. Competitor CAMs (HBeAg Negative*)** HBV DNA Most Advanced Mean Decline Drug Name Dose Status from BL to EOT % < LLOQ at Day 28 (Log10 IU/mL) ALG-000184 Phase 1 10 mg 3.7 100 ABI-H07311,2 Phase 2a 300 mg 2.5 25 JNJ-63793,4 Phase 2 250 mg 2.7 56 200 mg 2.9 N/A
Slide 26: Part 3 HBsAg Reductions in 28-Day Monotherapy
ALG-000184 - Part 3 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) ALT Nucleoside Analog Nucleoside Analog HBV DNA HBsAg Day Max HBsAg reduction: 0.52 log10 IU/mL 0.23 log10 IU/mL 0.35 log10 IU/m
Slide 27: Part 4 Cohort Designs
ALG-000184-201 - Part 4 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 ETV (ETV only) Cohort 1 x 12 weeks x 12 weeks x 8 weeks N=11 E+ China N=8 Randomize Follow-up 3 active:1 placebo ALG-000184 3
Slide 28: Part 4 Cohort 2 & B Baseline Characteristics
ALG-000184-201 - Part 4 Cohort 2 & B Baseline Characteristics P4C2 P4CB Characteristic (n=15*) (n=10) Age, years, mean (SEM) 31.4 (3.3) 36.8 (2.9) Male, n(%) 8 (53) 7 (70) Asian, n(%) 3 (100) 9 (90) BMI, kg/m2, mean (SEM) 22.2 (0.8) 22.4 (0.8) HBV Genotype, n(%) B: 5 (33); C: 10 (67) B: 5 (50); C: 4
Slide 29: Antiviral Effect - HBV DNA Change from Baseline
Antiviral Effect - Part 4 Cohort 2 & B 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 w
Slide 30: Antiviral Effect: HBV Antigen Change from Baseline
ALG-000184-201 - Antiviral Effect: Part 4 Cohort 2 & B 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 sub
Slide 31: Antiviral Effect: Cohorts 1 vs. 2 HBV Antigen Change
ALG-000184-201 - Antiviral Effect: Part 4 Cohorts 1 vs. 2 HBV Antigen Change from Baseline HBcrAg Number of subjects at timepoint ALG-000184 treatment results in dose-dependent HBsAg, HBeAg and HBcrAg declines Yuen, M-F. et al., Late Breaker Poster #5028-C, AASLD (2023). 30
Slide 32: Antiviral Effect: HBV Antigen Change from Baseline
ALG-000184-201 - Antiviral Effect: Part 4 Cohort 2 & B HBV Antigen Change from Baseline Treatment ETV x 12 weeks Number of subjects at timepoint 6 6 6 5 Visit (Weeks) • ETV alone only impacted HBV DNA; no impact on HBV RNA or antigens Yuen, M-F. et al., Late Breaker Poster #5028-C, AASLD (2023). 31
Slide 33: Safety Overview Treatment Emergent Adverse Events
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↑
Slide 34: Antiviral Effect: ALT, HBsAg, HBeAg and HBcrAg Over Time
Antiviral Effect ALT, HBsAg, HBeAg and HBcrAg Over Time by Subject – P4C2 (300 mg ALG-000184 + ETV x ≤96 wks) Part 4 Cohort 2 All subjects (n=12) observed HBcrAg declines after receiving 300 mg ALG-000184 + ETV x ≥ 12 weeks 11/12 had HBeAg declines and 9/12 had HBsAg reductions ALT flares seen in co
Slide 35: ALG-000184 Multiple Development Paths Available
ALG-000184 Multiple Development Paths Available Endpoint Affected Viral Markers Approvable Endpoint* In Functional Cure HBsAg, DNA US, EMEA, China Partial Cure HBsAg, DNA TBD DNA Suppression DNA US, EMEA, China (Used for tenofovir alafenamide (TAF) approval) *Endpoints defined in regulatory guidance
Slide 36: Chronic Suppression Well Defined, Validated Approval Pathway
Chronic Suppression Well Defined, Validated Approval Pathway • Definition: HBV DNA <LLOQ at Week 48 • Pathway endorsed by FDA, EMEA, and China FDA (CDE) – Relevant language (FDA): – Pathway was used to get tenofovir alafenamide (TAF; Gilead) approved in all 3 regions HBV Guidance from: FDA 2022; EME
Slide 37: Executive Summary ALG-000184
Executive Summary ALG-000184 • Oral dosing with 300 mg ALG-000184 ± ETV x ≤48 weeks in untreated HBeAg+ CHB subjects results in: – A favorable safety profile – Greater suppression of HBV DNA and RNA vs. ETV alone (1st MOA) – No viral breakthrough when ALG-000184 is given as monotherapy x ≤44 weeks –
Slide 38: Coronavirus
Coronavirus • ALG-097558 (CoV Protease Inhibitor) 37
Slide 39: ALG-097558 Aligos' Potent COVID-19 Protease Inhibitor
ALG-097558 Aligos’ Potent COVID-19 Protease Inhibitor • Despite the availability of prophylactic vaccines, a need for therapeutics still exists – New variants are continuously emerging – Large segments of global population lack access to, or are opposed to, vaccination – Especially needed to prevent
Slide 40: ALG-097558 Best-In-Class Potential vs. Other Oral Protease Inhibitors
ALG-097558 Best-In-Class Potential vs. Other Oral Protease Inhibitors Aligos Pfizer Shionogi Sorrento Enanta Parameters ALG-097558 Nirmatrelvir/RTV Ensitrelvir Olgotrelvir EDP-235 (preclinical) (authorized – global) (authorized – Japan) (Phase 3) (Phase 2) SARS-CoV-2 variants/subvariants*
Slide 41: ALG-097558 Phase 1 Safety & PK
ALG-097558 Phase 1 Safety & PK – Dosing in Healthy Volunteers Initiated Part 1: Part 2: Part 3: Single Ascending Multiple Ascending Midazolam Dose/Food Effect Dose Drug-Drug Interaction (Ongoing) Part 4: Itraconazole Drug-Drug Interaction Part 5 (OPTIONAL): Carbamazepine Drug-Drug Interaction Part 6
Slide 42: ALG-097558 Coronavirus Protease Inhibitor Drug Candidate
ALG-097558 Coronavirus Protease Inhibitor Drug Candidate • Potent pan-coronavirus protease inhibitor drug candidate – Additional candidates from the series advancing as backup compounds • Superior preclinical profile versus nirmatrelvir (Pfizer) – 6-27 fold more potent in biochemical and cell-based
Slide 43: Executive Summary
Executive Summary Aligos Advancing Multiple Promising Drugs in Areas of Unmet Need • MASH – ALG-055009 (THR-β agonist) - enhanced PK, pharmacology vs. competitor THR-β drugs; US IND cleared – Phase 2a study with ALG-055009 (12-week MRI-PDFF) – screening ~Q1 2024, topline data ~Q4 2024 – Oligonucleot
Slide 44: Aligos Therapeutics
ALIGOS THERAPEUTICS
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