Aligos Therapeutics, Inc. · NASDAQ:ALGS
Aligos Therapeutics — Investor Presentation (September 2022)
42 slides from Aligos Therapeutics's investor presentation, September 2022
Slide 1: Corporate Presentation September 2022
Lawrence M. Blatt, Ph.D. Chairman, CEO & Co-Founder C Corporate Presentation September 2022
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 Data Readouts Planned Throughout 2022 Candidate Indication MOA 2022-3 Clinical Trial Timelines* & Data Readouts Q2 Q3 Q4 Q1 28 days in CHB Dosing x 12-weeks in CHB ALG-000184 CHB CAM-II AASLD (28 days CHB) Phase 1 enabling nonclinical studies SAD in HV + CHB ALG
Slide 4: Aligos Discovery Pipeline
Aligos Discovery Pipeline Multiple Candidates Advancing Towards Development Anticipated Candidate Indication MOA Discovery Nonclinical Phase 1 Milestones Compound Discovery CHB CAM-I Nomination Compound Discovery CHB PD-L1 Nomination Compound Discovery NASH Oligonucleotide Nomination Compound Discov
Slide 5: Coronavirus
Coronavirus • ALG-097558 (CoV Protease Inhibitor) 4
Slide 6: 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 – Resistant variants are emerging and may become dominant (e.g., Omicron) – Large segments of global population lack access to, or are opposed to, vaccinati
Slide 7: 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) PF-07321332 2.92 0.91 2.03 PBI-0451 3.6 1.74 3.4 S-217622 4.0 1.31 2.6 ALG-097558 0.26 1.992 0.074 ALG-097558 Ki is 27-46 fold more potent vs. competitors in the 3CLpro biochemical assay 1The as
Slide 8: 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 Pardes Shionogi Pfizer Aligos PBI-0451 S-217622 PF-07321332 ALG-097558 03021/2020 n.d. n.d. 0.116 0.010 Vero E6+CP B.1.1.7 (alpha) 0.038 0.023 0.099 0.012 A549-ACE2-TMPRSS2 SARS-CoV-2 B.1.617.2 (
Slide 9: ALG-097558 Oral Prophylactic Treatment in the Hamster Model
ALG-097558 Oral Prophylactic Treatment in the SARS-CoV-2 Hamster Model 7 Dosing (BID) 6 Log10 TCID50/mg lung Ritonavir (RTV), 50 mg/kg Amount of 5 RTV/ALG-097558, 50/25 mg/kg Infectious Virus RTV/ALG-097558, 50/50 mg/kg at Day 4 4 RTV/ALG-097558, 50/100 mg/kg RTV/ALG-097558, 50/150 mg/kg 3 PF-073213
Slide 10: ALG-097558 Oral Therapeutic Treatment in the 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 Amount of 7 Log10 TCID50/mg lung RTV/ALG-097558, 50/75 mg/kg Infectious Virus 6 RTV/ALG-097558, 50/25 mg/kg 8-hr delay at Day 4 5 RTV/ALG-097558, 50/75 mg/kg 4 2
Slide 11: ALG-097558 SARS-CoV-2 3CLpro Triple 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) PF-07321332 (Pf
Slide 12: 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 PF-07321332 (Pfizer) – 7-27 fold more potent in biochemical and cell-based a
Slide 13: Chronic Hepatitis B
ALIGOS THERAPEUTICS Chronic Hepatitis B
Slide 14: Therapeutic Approaches to CHB Functional Cure
Therapeutic Approaches to CHB Functional Cure Inhibit Viral Replication Lower Antigen Burden Boost Immune Response 13
Slide 15: Clinical Strategy for CHB Functional Cure
Chronic Hepatitis B Clinical Strategy for CHB Functional Cure MOA #1 Healthy Volunteers Patients Combination Protocol MOA #2 Healthy Volunteers Patients Multiple combinations of CAM, siRNA and PD-L1 Pivotal Trial(s) +/- SOC in patients with CHB x 24-48 week treatment MOA #3 Healthy Volunteers Patien
Slide 16: Inhibiting Viral Replication
Inhibiting Viral Replication • ALG-000184 (Class-II CAM) 15
Slide 17: ALG-000184 In Vitro Potency vs. Competitor Class-II CAMs
ALG-000184 In Vitro Potency vs. Competitor Class-II CAMs HBV DNA reduction Compound Current Status Cell Type (EC50 nM) Vebicorvir Discontinued 172 AD38 Assembly ABI-H3733 Phase 1 5 AD38 Janssen JNJ-6379 Phase 2 54 HepG2.117 Enanta EDP-514 Phase 1 17 HepG2.115 Arbutus AB-836 Phase 1 10 HepDE19 0.63 H
Slide 18: 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 19: ALG-000184-201 Part 3 Cohorts 1-4 Antiviral Activity Data
ALG-000184-201 Part 3 Cohorts 1-4 Antiviral Activity Data 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 HBeAg- CHB subjects: Similar HBV DNA reduction for 10, 50 and 100
Slide 20: ALG-000184 Antiviral Activity vs. Competitor CAMs
ALG-000184 Antiviral Activity vs. Competitor CAMs (HBeAg Negative*) HBV DNA Drug Name Current Status Dose Mean Decline from BL to EOT % < LLOQ at (Log10 IU/mL) Day 28 Vebicorvir1,2 Discontinued 300 mg 2.5 25 JNJ-63793,4 Phase 2 250 mg 2.7 56 200 mg 2.9 N/A EDP-5145 Phase 1b 800 mg 3.4 N/A AB-8366 Ph
Slide 21: HBeAg+ Chronic Infection: Growing Realization of Unmet Medical Need
HBeAg+ Chronic Infection (Immune Tolerant) Growing Realization of Unmet Medical Need • Patients with HBeAg+ chronic infection have high DNA and HBsAg levels • Baseline HBV DNA levels correlate with HCC, cirrhosis risk* – Reducing DNA levels decreases integrations, which are thought to be related to
Slide 22: ALG-000184 Phase 1-2 Clinical Development Pathways
ALG-000184 Phase 1-2 Clinical Development Pathways Phase 1 Phase 2 HBeAg+ CHB 100 mg + NA Chronic HBV 10-100 mg x 1-3 years HBeAg+ IT DNA Suppression x 12-48 weeks CAM + NA in HBeAg+ CHB subjects Endpoint: HBV DNA suppression at Wk48 TN and VS CHB 300 mg 300 mg + NA HBV 300 mg + NA +/- IFN HBeAg+ TN
Slide 23: Inhibiting Viral Replication
Inhibiting Viral Replication • Class-I CAM 22
Slide 24: Class-I Capsid Assembly Modulators
Class-I Capsid Assembly Modulators • Class-I capsid assembly modulators are orally bioavailable small molecules that result in large aberrant particles and decrease HBsAg in the AAV-HBV mouse • Publicly disclosed Class-I CAMs are in the heteroaryl pyrimidine (HAP) class – GLS4 and RG7907 are two cli
Slide 25: ALG-005398 In Vitro Potent Class-I CAM
ALG-005398 In Vitro Potent Class-I CAM • ALG-005398 potency in HepG2.117 cells – Reduction in HBV DNA › EC50 = 3.4 nM › EC90 = 10.6 nM • Demonstration of class-I CAM properties – Formation of large aberrant capsids ALG-005398 is a non-HAP Class-I CAM demonstrating excellent in vitro potency Debing e
Slide 26: ALG-005398 In Vivo Proof of Concept in the AAV-HBV Mouse Model
ALG-005398 In Vivo Proof of Concept in the AAV-HBV Mouse Model HBV DNA -6.4 log10 HBsAg -2.4 log10 HBeAg ALT ALG-005398 was dosed at 30 mg/kg/day BID for 96 days ALG-005398 is a non-HAP Class-I CAM that reduces HBsAg and other antigens in vivo Debing et. al., AASLD 2021. 25
Slide 27: Lowering S-Antigen Burden
Lowering S-Antigen Burden • ALG-125755 (siRNA) 26
Slide 28: 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 29: 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 30: Boosting the Immune Response
Boosting the Immune Response • ALG-093453 (PD-L1 Small Molecule) 29
Slide 31: 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 32: ALG-093453 PD-L1 Inhibitor
ALG-093453 PD-L1 Inhibitor T cell Activation T cell Activation Jurkat-NFAT assay PBMC from HBV Positive Donor ALG-093453 activates HBV specific T cells with low nM potency, similar to nivolumab and durvalumab 31
Slide 33: NASH
NASH ALG-055009, small molecule THR-β agonist 32
Slide 34: ALG-055009 More Potent and Selective In Vitro than MGL-3196 and VK-2809
ALG-055009 More Potent and Selective In Vitro than MGL-3196 and VK-2809 Relative THR-α and THR-β Activity in Cell-Based Assays In vitro, ALG-055009 is 5-47x more potent compared to Resmetirom (MGL-3196) and 2-3x more selective for THR-β than VK-2809* High β selectivity and potency may improve risk-b
Slide 35: ALG-055009 Best In Class Potential vs. 1st Gen THR-β Agonists
ALG-055009 Best In Class Potential vs. 1st Gen THR-β Agonists Parameter VK-2809 MGL-3196 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 (NTCP) AUC/Cm
Slide 36: ALG-055009 Development Timelines
ALG-055009 Development Timelines* ALG-055009 SAD in HV Ph2-enabling (THR-β) MAD in hyperlipidemia subjects Nonclinical Studies 2022 2023 Q1 Q2 Q3 Q4 Q1 SAD and MAD complete – data to be presented at AASLD 2022 SAD – Single ascending doses; MAD- Multiple ascending doses; HV – Healthy volunteers. *Tim
Slide 37: Study ALG-055009-301 SAD Interim Data – Safety, PK
Study ALG-055009-301 SAD Interim Data – Safety, PK • Study Design – Part 1 (SAD) - cohorts randomized to a single oral dose of ALG-055009 (N=6) or placebo (N=2) › Dose levels: 0.1, 0.3, 0.9, 2.6, 4 mg • Safety: well tolerated – No serious adverse events, premature discontinuations, Grade ≥3 treatmen
Slide 38: Study ALG-055009-301 SAD Interim Data - PD
Study ALG-055009-301 SAD Interim Data - PD • Expected thyromimetic effects observed: generally dose proportional – Increases in Sex Hormone Binding Globulin (target engagement) – Decreases in thyroid hormones (TSH, T3, T4) – Decreases in lipids (triglycerides, LDL, ApoB, etc.) Expected thyromimetic
Slide 39: ALG-055009 Summary
ALG-055009 Summary • More potent, β-selective vs. frontrunner THR-β compounds • Predictable and dose-proportional PK properties • Phase 1 proof of concept study – SAD in HV – complete › Well tolerated, linear PK (supports QD dosing), expected thyromimetic effects observed – MAD (dosing x 14 days in
Slide 40: Our NASH Strategy
Our NASH Strategy • Advance ALG-055009 through Phase 1 proof of concept study – Benchmark safety, PK, anti-lipid data vs. resmetirom & VK2809 Phase 1 data • Resmetirom Phase 3 readout expected in Q4 2022 • Aligos NASH ALG-055009 program has strong optionality in 2023 – Continue to advance program on
Slide 41: Aligos Therapeutics Summary
Aligos Therapeutics Summary • We are advancing multiple drug candidates with clinically-validated MOAs with the goal of rapidly developing optimized combination regimens – Coronavirus Protease Inhibitor (ALG-097558) › Targeting to complete FIH enabling nonclinical studies and file Phase 1 CTA in Q1
Slide 42: Aligos Therapeutics
ALIGOS THERAPEUTICS
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