Aligos Therapeutics, Inc. · NASDAQ:ALGS
Aligos Therapeutics — Investor Presentation (January 2023)
47 slides from Aligos Therapeutics's investor presentation, Jan 24, 2023
Slide 1: Corporate Presentation
Corporate Presentation C January 24, 2023
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: Milestones/Data Readouts Anticipated in 2023
Aligos Development Portfolio Multiple Milestones/Data Readouts Anticipated in 2023 Candidate Indication MOA 2023 Clinical Trial Timelines and Data Readouts Q1 Q2 Q3 Q4 Phase 2 THR-β Phase 2 Enabling Activities CTA CTA ALG-055009 Phase 1 (GLP Toxicology, Drug Product Supply) Agonist APASL (SAD/MAD da
Slide 4: NASH
NASH ALG-055009, small molecule THR-β agonist 3
Slide 5: ALG-055009 Summary
ALG-055009 Summary • Discovered by Aligos – issued US patent expires 2040 • More β-selective, >50 fold more potent than resmetirom • Phase 1 – Safety – well tolerated without clinical safety signals – PK - favorable profile (linear, low variability) that is differentiated vs. resmetirom › More unifo
Slide 6: Characteristics of Commercially Successful Drugs
Characteristics of Commercially Successful Drugs • Two main types of commercially successful drugs – First to market – Best in market (seldom the first) • Top Selling Drugs Drug Name Cumulative Timing to Enter Value Market Atorvastatin (Lipitor) $150B 5 Adalimumab (Humira) $109B 3 Clopidogrel (Plavi
Slide 7: Resmetirom Phase 1 MAD Data
Resmetirom Phase 1 MAD Data Nonlinear PK 100 mg 80 mg A 25% increase in dose (80 mg 100 mg) results in a ~300% increase in exposure MAD data at Day 14 from Taub et al, Atherosclerosis, 2013 6
Slide 8: Resmetirom Ph2 Data MRI-PDFF
Resmetirom Ph2 Data MRI-PDFF • Study design – 125 NASH subjects randomized in a 2:1 ratio to resmetirom or placebo x 36 weeks – Starting dose (4 weeks) 80 mg. Dose titrated at Week 4 based on Week 2 PK › 53% of resmetirom subjects had their dose titrated up (100 mg) or down (40-60 mg) – Endpoints: M
Slide 9: Resmetirom Ph2 Data Liver Biopsy
Resmetirom Ph2 Data Liver Biopsy MRI-PDFF de-fatting correlated with histologic improvement Loomba et al, EASL 2020 8
Slide 10: Hypothetical Impact of PK Variability on Efficacy/Safety
Hypothetical Impact of PK Variability on Efficacy/Safety High Exposure Range Drug Exposure (AUC) (Suboptimal safety risk) 1 SD Mean Mean Desirable Exposure Range 1 SD (Optimal safety/efficacy) Low Exposure Range (Suboptimal efficacy risk) Drug A Drug B High Variability (100% CV) Low Variability (25%
Slide 11: ALG-055009 More Potent and Selective In Vitro than Resmetirom and VK-2809
ALG-055009 More Potent and Selective In Vitro than Resmetirom and VK-2809 Relative THR-α and THR-β Activity in Cell-Based Assays Relative THR-B Selectivity EC50 α (nM) EC50 β (nM) (α/β) ALG-055009 191 50 3.8 Resmetirom 5927 2366 2.5 VK-2809 Parent 366 269 1.4 T3 14.2 11.6 1.2 In vitro, ALG-055009 is
Slide 12: ALG-055009 Best In Class Potential vs. 1st Generation THR-β Agonists
ALG-055009 Best In Class Potential vs. 1st Generation THR-β Agonists Parameter VK-2809 Resmetirom ALG-055009 28 day mouse DIO TC, LDL lowering 28% 28% Up to 44% Percent of patients with ≥30% change 76%-100% 60% High Expected from baseline in MRI-PDFF (Ph2) Efficacy BCRP, OATP substrate ? Yes No (NTC
Slide 13: ALG-055009 Phase 1 Study Design
ALG-055009 Phase 1 Study Design 4 mg 1.0 mg 2.6 mg 0.5 mg 0.9 mg 0.3 mg 0.6 mg 0.1 mg 0.3 mg 12
Slide 14: Study ALG-055009-301 SAD - PK, Safety, Biomarkers
Study ALG-055009-301 SAD - 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), premature discontinuations, Grade ≥3
Slide 15: Study ALG-055009-301 MAD - PK, Safety
Study ALG-055009-301 MAD - PK, Safety • Oral doses evaluated: 0.3, 0.5, 0.6, and 1.0 mg QD x 14 days • PK: favorable profile (dose-proportional, low variability (≤27%), 2x accumulation) • Safety: well tolerated, no clinical evidence of hypo or hyperthyroidism – No SAEs, discontinuations – All TEAEs
Slide 16: MAD - Biomarkers Expected Thyromimetic Effects Observed
MAD - Biomarkers Expected Thyromimetic Effects Observed Dosing Period Dose proportional increases in SHBG Charfi et al., AASLD 2022. 15
Slide 17: MAD - Biomarkers Expected Thyromimetic Effects Observed
MAD – Biomarkers Expected Thyromimetic Effects Observed Day Dose responsive reductions in lipids (e.g., LDL, Apo-B, Triglycerides) Charfi et al., AASLD 2022. 16
Slide 18: ALG-055009 Summary
ALG-055009 Summary • Discovered by Aligos – issued US patent expires 2040 • More β-selective, >50 fold more potent than resmetirom • Phase 1 – Safety – well tolerated without clinical safety signals – PK - favorable profile (linear, low variability) that is differentiated vs. resmetirom › More unifo
Slide 19: Coronavirus
Coronavirus • ALG-097558 (CoV Protease Inhibitor) 18
Slide 20: 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 21: ALG-097558 Superior Biochemical Potency Against SARS-CoV-2
ALG-097558 Superior Biochemical Potency Against SARS-CoV-2 SARS-CoV-2 3CLpro IC50 (nM)1 Hillslope Ki (nM) ALG-097558 0.26 1.992 0.074 Nirmatrelvir 2.92 0.91 2.03 PBI-0451 3.6 1.74 3.4 Ensitrelvir 4.0 1.31 2.6 ALG-097558 Ki is 27-46 fold more potent vs. competitors in the 3CLpro biochemical assay 1Th
Slide 22: ALG-097558 Superior Biochemical Potency Against 3CLpro
ALG-097558 Superior Biochemical Potency Against 3CLpro Derived from SARS-CoV-2, MERS and Other Human CoV’s IC50 (μM) SARS-CoV-2 Virus MERS HKU-1 229E NL63 (Wuhan) Enzyme Concentration (nM) 25 100 12.5 50 50 ALG-097558 0.009 0.106 0.008 0.033 0.049 Nirmatrelvir 0.021 0.422 0.038 0.185 0.558 PBI-451 0
Slide 23: ALG-097558 Superior Cell-Based Potency Against SARS-CoV-2 and Variants
ALG-097558 Superior Cell-Based Potency Against SARS-CoV-2 and Variants EC50 (μM) Virus Variant/Cell line PBI-0451 Ensitrelvir Nirmatrelvir ALG-097558 03021/2020 1 n.d. n.d. 0.114 0.012 B.1.1.7 (alpha) 2 0.038 0.022 0.106 0.011 B.1.617.2 (delta) 2 0.126 0.141 0.217 0.013 SARS-CoV-2 B.1.1.529 (omicron
Slide 24: ALG-097558 Oral Therapeutic Treatment in the SARS-CoV-2 Hamster Model
ALG-097558 Oral Therapeutic Treatment in the SARS-CoV-2 Hamster Model ✱✱ ✱✱ 9 ✱✱ Dosing (BID) ✱✱ 8 Ritonavir (RTV), 50 mg/kg ✱✱ 0-hr delay 7 Log10 TCID50/mg lung RTV/ALG-097558, 50/75 mg/kg Amount of 6 RTV/ALG-097558, 50/25 mg/kg Infectious Virus 8-hr delay 5 RTV/ALG-097558, 50/75 mg/kg on Day 4 4 2
Slide 25: ALG-097558 SARS-CoV-2 3CLpro L50F E166A L167F Mutant
ALG-097558 SARS-CoV-2 3CLpro L50F E166A L167F Mutant • ALG-097558 has the least loss of activity against a triple mutant conferring resistance to other SARS-CoV-2 PIs Biochemical VeroE6+CP Compound Name L50F/E166A/L167F L50F/E166A/L167F (fold change versus WT) EC50 [µM] (fold change) ALG-097558 (Ali
Slide 26: 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 27: Chronic Hepatitis B
ALIGOS THERAPEUTICS Chronic Hepatitis B
Slide 28: Therapeutic Approaches to CHB Functional Cure
Therapeutic Approaches to CHB Functional Cure Inhibit Viral Replication Lower Antigen Burden Boost Immune Response 27
Slide 29: Inhibiting Viral Replication
Inhibiting Viral Replication • ALG-000184 (CAM-E) 28
Slide 30: ALG-000184 Phase 1 Study in CHB Subjects
ALG-000184 Phase 1 Study in CHB Subjects Multiple Doses in Currently Not Treated/Treatment Naïve CHB Subjects HBV DNA > 2000 IU/mL, HBeAg- or HBeAg+ Up to 6 cohorts (n=10 per Cohort, n=8 ALG-000184, n=2 Placebo) 28 daily oral doses Endpoints: PK, safety, antiviral activity (e.g., DNA, RNA) Endpoint
Slide 31: ALG-000184-201 Part 3 Antiviral Activity – HBV DNA and HBV RNA
ALG-000184-201 Part 3 Cohorts 1-5 Antiviral Activity – HBV DNA and HBV RNA Mean (SEM) Serum HBV DNA and HBV RNA Levels Change from Baseline Through the End of Study HBV DNA* HBV RNA** % <LLOQ % <LLOQ --- 100 --- 100 --- 83 --- 100 --- 75 --- 100 --- 0 --- 0 --- 0 --- 0 HBeAg- CHB subjects: Similar H
Slide 32: ALG-000184 Antiviral Activity vs. Competitor CAM-Es (HBeAg Negative)
ALG-000184 Antiviral Activity vs. Competitor CAM-Es (HBeAg Negative) HBV DNA Drug Name Current Status Dose Mean Decline from BL to EOT % < LLOQ at Day 28 (Log10 IU/mL) ALG-000184 Phase 1 10 mg 3.7 100 200 mg 2.9 N/A EDP-5145,** Phase 1b 800 mg 3.4 N/A Vebicorvir1,2 Discontinued 300 mg 2.5 25 JNJ-637
Slide 33: ALG-000184 HBsAg Reductions Observed in 28-Day Monotherapy
ALG-000184 HBsAg Reductions Observed in 28-Day Monotherapy 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/mL 0.78 log10 IU/mL
Slide 34: ALG-000184-201 Part 4 Study Design – up to 48 Weeks of Dosing
ALG-000184-201 Part 4 Study Design – up to 48 Weeks of Dosing Randomize N=8 3 active:1 placebo Follow-up (+ ETV) ALG-000184 100 mg + ETV x 24 weeks Cohort 1 x 8 weeks N=11 Placebo + ETV N=2 ALG-000184 + ETV Follow-up (+ ETV) x 12 weeks x 12 weeks x 8 weeks Randomize N=8 3 active:1 placebo Follow-up
Slide 35: ALG-000184 + ETV Lowers DNA/RNA More Than ETV Alone
ALG-000184-201 (Part 4) ALG-000184 + ETV Lowers DNA/RNA More Than ETV Alone HBV DNA HBV RNA Reduction at Week 10 Placebo + ETV, N=3 ALG-000184 100 mg + ETV, N=7 ALG-000184 300 mg + ETV, N=6 HBV DNA, mean (SEM) log10 IU/mL -3.7 (0.43) -4.9 (0.28) -5.2 (0.3) HBV RNA, mean (SEM) log10 copies/mL 0.08 (0
Slide 36: 300 mg ALG-000184 + ETV Lowers HBsAg Over Time
ALG-000184-201 (Part 4) 300 mg ALG-000184 + ETV Lowers HBsAg Over Time 100 mg 300 mg Clear downward trend over 10 weeks for HBsAg among majority of 300 mg ALG-000184 treated subjects Data on file. 35
Slide 37: ALG-000184-201 Ongoing Phase 1b Cohorts
ALG-000184-201 Ongoing Phase 1b Cohorts • Enrollment/dosing in multiple longer duration (≤48 weeks) cohorts is ongoing • Cohorts designed to address several key questions, including – Impact of treatment with/without entecavir – Antiviral activity in different patient populations (high/normal baseli
Slide 38: Lowering S-Antigen Burden
Lowering S-Antigen Burden • ALG-125755 (siRNA) 37
Slide 39: ALG-125755 Discovery and Advancement of a Differentiated siRNA
Short Interfering Nucleic Acid ALG-125755 Discovery and Advancement of a Differentiated siRNA • siRNAs have demonstrated clinical validation in CHB infected patients • We have designed our siRNA sequences using our proprietary technology and liver targeting conjugation to maximize in vitro and in vi
Slide 40: ALG-125755 Repeat Dosing in the AAV-HBV Mouse Model vs. VIR-2218
ALG-125755 Repeat Dosing in the AAV-HBV Mouse Model vs. VIR-2218 VIR-2218* ALG-125755 Mean Log10 IU/mL HBsAg Reduction Relative to Day 0 Mean Log10 IU/mL HBsAg Reduction Relative to Day 0 ALG-125755 demonstrates a more sustained reduction in HBsAg vs. competitor siRNAs *Data from Anglero-Rodriguez Y
Slide 41: ALG-125755-501 Study Timelines
ALG-125755-501 Study Timelines Part 1 SAD HV Parts 2-3 - SAD, MAD in CHB SAD in HV Readout SAD in CHB Cohort 1 Readout (APASL) (EASL) Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep 2023 SAD in HV: Part 1 Cohorts 1-4 (20 mg, 60 mg, 100 mg and 200 mg) completed dosing SAD in CHB: Part 2 Cohort 1 enrollme
Slide 42: Clinical Experience with siRNAs
Clinical Experience with siRNAs HBsAg Reduction After 28 Days in CHB Patients Mean HBsAg change from baseline (Log10 IU/mL) Weeks Consistent reductions of ~0.5 log10 IU/mL noted for competitor siRNAs 28 days after a single dose Data derived from multiple studies: VIR-2218, Yuen et al., AASLD 2022; A
Slide 43: Boosting the Immune Response
Boosting the Immune Response • Liver Targeted Oral PD-L1 Inhibitor (Small Molecule) 42
Slide 44: PD-L1 Inhibitors
PD-L1 Inhibitors • Exhaustion of HBV specific T-cells contributes to the persistence of CHB • Proof of concept in CHB with anti-PD1 antibodies has been established – Multiple clinical studies have demonstrated HBsAg reductions in CHB infected patients • Aligos has discovered several potent series of
Slide 45: Aligos CHB Portfolio Key Pillars for Enhanced Functional Cure Rates
Aligos CHB Portfolio Consists of the Key Pillars Which are Likely Necessary for Enhanced Functional Cure Rates Replication HBsAg Immune Inhibition Reduction Stimulation + + CAM-E Inhibitor siRNA PD–L1 inhibitor ALG-000184 ALG-125755 oral small molecule 44
Slide 46: Executive Summary
Executive Summary Aligos Advancing Multiple Promising Drugs in Areas of Unmet Need • NASH – THR-β agonist (ALG-055009) – more uniform exposure vs. competitor THR-β drugs may lead to more consistent efficacy and safety – Merck oligonucleotide collaborations are progressing • Coronavirus Protease Inhi
Slide 47: Aligos Therapeutics
ALIGOS THERAPEUTICS
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