Aligos Therapeutics, Inc. · NASDAQ:ALGS
Aligos Therapeutics — Investor Presentation (April 2021)
46 slides from Aligos Therapeutics's investor presentation, April 2021
Slide 1: Corporate Presentation
Lawrence M. Blatt, Ph.D. CEO & Co-Founder C Corporate Presentation
Slide 2: Disclosures
Disclosures This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy, prospective drugs and drug candidates
Slide 3: Aligos Therapeutics Highlights
Aligos Therapeutics Highlights Our Mission Our Platforms Our Strategy Our Team Develop novel therapeutics to Proprietary oligonucleotide Develop pharmacologically Decades of drug discovery address unmet medical needs and small molecule platforms optimized drug candidates and development experience i
Slide 4: Our Platforms, Capabilities and Collaborations
Our Platforms, Capabilities and Collaborations Oligonucleotide Modalities Emory University CAM IP & Collaboration Small Molecule Chemistry Luxna Biotech 3rd Generation XNA Nucleotides Chemistry, Manufacturing AM Chemicals and Controls Proprietary GalNAc Merck (MSD) NASH Biological Sciences Collabora
Slide 5: A Lesson from Chronic Hepatitis C
A Lesson from Chronic Hepatitis C From First Movers to Best-in-Class Regimens • Efficacy Safety Convenience • Standard of care treatment until 2011 – Pegylated interferon + ribavirin – 48-weeks, ~50% cure rate, poorly tolerated • Protease inhibitors – First clinical entrant – BILN-2061 (2001) –
Slide 6: Our Pipeline
Our Pipeline Anticipated Candidate Indication MOA Discovery Nonclinical Phase 1 Phase 2 Phase 3 Milestones Initial ALG-010133 CHB STOPS Phase 1 Data Initial ALG-000184 CHB CAM Phase 1 Data Phase 1 ALG-020572 CHB ASO Start Phase 1 ALG-125755 CHB siRNA Start Phase 1 ALG-055009 NASH THR-β Agonist Start
Slide 7: Chronic Hepatitis B
ALIGOS THERAPEUTICS Chronic Hepatitis B
Slide 8: CHB Epidemiology & Our Portfolio
CHB Epidemiology & Our Portfolio • CHB Epidemiology* - Most common chronic viral infection in world – >290 million carriers worldwide (2020) – ~8 million in US, EU, Japan (2015) – Responsible for ~900,000 deaths/year (2015) • Our Portfolio – Potentially best-in-class drug candidates against validate
Slide 9: Chronic Hepatitis B vs. Functional Cure
Chronic Hepatitis B vs. Functional Cure Outcome Determined by Balance Between Virus and Host Immune Response Chronic Hepatitis B Functional Cure Therapeutics Tip the Balance Robust Viral Replication Direct Acting Antivirals No viral replication (High HBV DNA & RNA Levels) e.g., NA, CAM (undetectable
Slide 10: Our CHB Clinical Development Strategy
Our CHB Clinical Development Strategy SAD/MAD CHB Patients CAM in HV x 4 weeks SAD/MAD CHB Patients Combination Protocol STOPS in HV x 12 weeks Multiple combinations of CAM, STOPS and ASO/siRNA Pivotal Trial(s) SAD/MAD CHB Patients +/- SOC in patients with CHB ASO in HV x 4 weeks x 24-48 weeks treat
Slide 11: STOPS
STOPS ALG-010133, a novel, chemically optimized poly-AC oligonucleotide analog 10
Slide 12: STOPS Molecule ALG-010133
STOPS Molecule ALG-010133 Discovery and Advancement of a Potential Best-in-Class Agent • Poly AC oligonucleotides have clinical validation – REP 2139 has demonstrated a 39% functional cure in CHB infected patients* – Compound is delivered IV via a 2-hr infusion • Chemical optimization led to the dis
Slide 13: ALG-010133 Development Timelines
ALG-010133 Development Timelines* Approved Approved Approved ALG-010133-101 SAD/MAD in HV Multiple dosing CHB (STOPS) 2021 2022 Q1 Q2 Q3 Q4 Q1 EASL AASLD APASL SAD – Single ascending doses; MAD- Multiple ascending doses; HV – Healthy volunteers; CHB – Chronic hepatitis B *Timelines are approximate a
Slide 14: ALG-010133 Phase 1 Study Data in Healthy Volunteers
ALG-010133 Phase 1 Study Data In Healthy Volunteers Single/Multiple Ascending Dose (SAD/MAD) study in HV N=72; n=8 per Cohort, n=6 ALG-010133, n=2 Placebo Single (SAD) or Three weekly subcutaneous (SC) doses (MAD) SAD Follow-up N=8 Safety and PK of single doses of 20, 50, 75, 125, 160 and 200 mg N=2
Slide 15: ALG-010133 Phase 1 Study Data in CHB
ALG-010133 Phase 1 Study Data In CHB Multiple Doses in VS CHB Subjects N≤60 Subjects; n=10 per Cohort, n=8 ALG-010133, n=2 Placebo Up to 12 weekly doses Endpoints: PK, safety, antiviral activity (e.g., HBsAg) Endpoint data collected throughout, including Baseline Week 12 Week 24 N=8 N=8 ALG-010133 +
Slide 16: CAM
CAM ALG-000184, a prodrug of ALG-001075 15
Slide 17: Class-II CAM Molecule ALG-000184
Class-II CAM Molecule ALG-000184 Discovery and Advancement of a Potential Best-in-Class Agent • Capsid Assembly Modulators have clinical validation – Multiple CAMs have advanced into Phase 2 studies – Consistent HBV DNA and RNA reductions observed • Chemical optimization of GLP-26 led to the discove
Slide 18: ALG-000184 Development Timelines
ALG-000184 Development Timelines* Approved Approved Approved ALG-000184 SAD/MAD in HV Multiple dosing CHB (CAM) 2021 2022 Q1 Q2 Q3 Q4 Q1 EASL AASLD APASL SAD – Single ascending doses; MAD- Multiple ascending doses; HV – Healthy volunteers; CHB – Chronic hepatitis B *Timelines are approximate and sub
Slide 19: Study ALG-000184-201 SAD and MAD Completed
Study ALG-000184-201 SAD and MAD Completed Parts 1 and 2: Single and Multiple Ascending Doses in Healthy Volunteers. N=48; n=8 per Cohort, n=6 ALG-000184, n=2 Placebo Up to 7 oral daily doses SAD Follow-up Safety and PK of single doses of 40, 100, 250 and 500 mg MAD Follow-up Safety and PK of 7 dose
Slide 20: ALG-000184 Phase 1 Study Data in CHB
ALG-000184 Phase 1 Study Data In CHB Multiple Doses in Currently Not Treated/Treatment Naive CHB Subjects N≤60 Subjects; 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 data collected throughout, including Baseline
Slide 21: Additional Oligonucleotide Approaches
Additional Oligonucleotide Approaches • ALG-020572 (ASO) • ALG-125755 (siRNA) 20
Slide 22: Antisense Oligonucleotide ALG-020572
Antisense Oligonucleotide ALG-020572 Discovery and Advancement of a Highly Differentiated ASO • Antisense oligonucleotides have demonstrated clinical validation in CHB infected patients • We have optimized our sequences using our proprietary Luxna Biotech 3rd generation XNA nucleotides to enhance po
Slide 23: ALG-020572 in the Mouse AAV-HBV Model
ALG-020572 Our ASO Drug Candidate in the Mouse AAV-HBV Model Potent in vivo activity of ALG-020572 in the AAV-HBV mouse model without ALT elevation 22
Slide 24: ALG-020572 vs. GSK-836 ASO in the Mouse AAV-HBV Model
ALG-020572 Our ASO vs. GSK-836 ASO in the Mouse AAV-HBV Model 5.0 Serum HBsAg 4.5 Vehicle, SC, 6 doses HBsAg Log10 (IU/mL) ALG-020001 GSK-836, 3 mg/kg, SC, 6 doses ALG-020001 GSK-836, 10 mg/kg, SC, 6 doses 4.0 ALG-020572, 3 mg/kg, SC, 6 doses 3.5 ALG-020572, 10 mg/kg, SC, 6 doses 3.0 2.5 2.0 0 5 10
Slide 25: ALG-020572 Development Timelines
ALG-020572 Development Timelines* ALG-020572 Multiple (ASO) Ph1-enabling Nonclinical Studies SAD/MAD in HV dosing CHB 2021 2022 Q1 Q2 Q3 Q4 Q1 EASL AASLD APASL SAD/MAD in HV followed by multiple dosing in VS CHB Subjects Countries: New Zealand, Hong Kong, South Korea, China, UK, Moldova SAD – Single
Slide 26: Short Interfering Nucleic Acid ALG-125755
Short Interfering Nucleic Acid ALG-125755 Discovery and Advancement of a Differentiated siRNA • siRNAs have demonstrated clinical validation in CHB infected patients • We have optimized our siRNA sequences using our proprietary technology and liver targeting conjugation to maximize in vitro and vivo
Slide 27: ALG-125755 siRNA in the Mouse AAV-HBV Model
ALG-125755 siRNA Drug Candidate in the Mouse AAV-HBV Model Potent and sustained antiviral activity following a single dose through 28-days of monitoring 26
Slide 28: ALG-125755 vs. VIR-2218 siRNA in the Mouse AAV-HBV Model
ALG-125755 Our siRNA vs. VIR-2218 siRNA in the Mouse AAV-HBV Model HBsAg in Serum 0.5 Log10 (IU/mL, mean ± SEM) Change in Serum HBsAg 0 Vehicle, 5 ml/kg, SC ALG-125852 VIR-2218, 1.5 mg/kg, SC, Day 0 ALG-125852 VIR-2218, 5 mg/kg, SC, Day 0 -0.5 ALG-125755, 1.5 mg/kg, SC, Day 0 ALG-125755, 5 mg/kg, SC
Slide 29: ALG-125755 Development Timelines
ALG-125755 Development Timelines* ALG-125755 Multiple (siRNA) Ph1-enabling Nonclinical Studies SAD in HV dosing CHB 2021 2022 Q3 Q4 Q1 Q2 Q3 AASLD APASL EASL SAD in HV followed by multiple dosing in VS CHB Subjects Countries: New Zealand, Hong Kong, South Korea, China, UK, Moldova SAD – Single ascen
Slide 30: Advancing CHB Development Compounds in Combination Studies
Aligos’ Advancing CHB Development Compounds in Combination Studies 29
Slide 31: STOPS ALG-010133 + ASO ALG-020572 In Vitro Combination
STOPS ALG-010133 + ASO ALG-020572 (unconjugated form) In Vitro Combination Shows Strong Synergy with no Cytotoxicity Unconjugated Analog of ALG-020572 + ALG-010133 Synergy Analysis (95% confidence interval) Synergy Volume +291.6 μM2% Unconjugated Analog ALG-010133 (nM) of ALG-020572 (nM) The synergy
Slide 32: STOPS ALG-010133 + CAM ALG-000184 In Vitro Combination
STOPS ALG-010133 + CAM ALG-000184 (ALG-001075) In Vitro Combination Shows Minor Synergy with no Cytotoxicity ALG-001075 + ALG-010133 Synergy Analysis (95% confidence interval) Synergy Volume +32.9 μM2% ALG-001075 (nM) ALG-010133 (nM) The synergy volume for the interaction between ALG-010133 and ALG-
Slide 33: ALG-125755 + ALG-020572 In Vitro Combination
ALG-125755 + ALG-020572 (Unconjugated Versions) In Vitro Combination Shows Minor Synergy with no Cytotoxicity ALG-020579 X ALG-125903 Synergy Analysis (95% confidence interval) Synergy Volume +46.0 μM2% ALG-020579 (pM) ALG-125903 (pM) Unconjugated ALG-020572 ASO Unconjugated ALG-125755 siRNA The syn
Slide 34: ALG-125755 + ALG-020572 In Vivo Combination Data
ALG-125755 + ALG-020572 In Vivo Combination Data in the Mouse AAV-HBV Model Log10 (IU/mL, mean ± SEM) Change in Serum HBsAg Vehicle, 5 mL/kg, SC ALG-125755, 5 mg/kg, SC, Day 0 ALG-020572, 5 mg/kg, SC, Days 0, 7, 14 ALG-125755 5 mg/kg, SC, Day 0 + ALG-020572, 5 mg/kg, SC, Days 0, 7, 14 siRNA x 1 dose
Slide 35: NASH
NASH ALG-055009, small molecule THR-β agonist 34
Slide 36: THR-β Agonists are Clinically Validated
THR-β Agonists are Clinically Validated THR-β agonists have demonstrated beneficial effects on serum lipid levels and liver histology ^All dose levels pooled. *Placebo corrected values. ** In patients with NASH, Harrison, Lancet, 2019. Resmetirom = MGL-3196. *** In patient with NAFLD, hyperlipidemia
Slide 37: 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 38: ALG-055009 Development Timelines
ALG-055009 Development Timelines* ALG-055009 SAD in HV (THR-β) Ph1-enabling Nonclinical Studies MAD in HV with hyperlipidemia 2021 2022 Q1 Q2 Q3 Q4 Q1 EASL AASLD APASL SAD in HV followed by MAD in HV with mild hyperlipidemia France SAD – Single ascending doses; MAD- Multiple ascending doses; HV – He
Slide 39: 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 – Data expected mid-2022 • Resmetirom Phase 3 and VK-2809 Phase 2b readouts are expected in H2 2022 • Aligos NASH program has strong optionality
Slide 40: Coronavirus
ALIGOS THERAPEUTICS Coronavirus
Slide 41: Our Approach to Developing a Broad Coronavirus Treatment
Our Approach to Developing a Broad Coronavirus Treatment • Despite the recent availability of prophylactic vaccines, a need for therapeutics still exists – Resistant variants are emerging and may become dominant – Large segments of global population are opposed to vaccination – Especially needed in
Slide 42: Recently Disclosed SARS-CoV Protease Inhibitors Potently Inhibit Cathepsin L
Recently Disclosed SARS-CoV Protease Inhibitors Potently Inhibit Cathepsin L Wichita State Wichita State University of Lübeck; University of Lübeck; Shanghai Institute of Reported Protease Materia Medica; University; University of Iowa; University; University of Iowa; Changchun Discovery Sciences Lt
Slide 43: ALG-097111 A Selective SARS-CoV-2 3C-Like Protease Inhibitor
ALG-097111 A Selective SARS-CoV-2 3C-Like Protease Inhibitor Biochemical Cellular SARS-CoV-2 (A549+ACE2): EC50= 200 nM SARS-CoV-2 inhibition in human SARS-CoV-2 3CLpro (IC50 = 7 nM) (similar potency confirmed for β-CoV OC43 small airway epithelial cell cultures human cathepsin L (IC50 > 10 µM) (HeLa
Slide 44: ALG-097111 Efficacy in SARS-CoV-2 Hamster Model
ALG-097111 Efficacy in SARS-CoV-2 Hamster Model ✱✱ 7 ✱✱ 6 Log10 TCID50/mg lung Infectious viral loads in the lungs of 5 RTV + Vehicle 60% PEG400 in water, subcutaneous[SC]) + ritonavir (50 mg/kg/dose, BID oral gavage) SARS-CoV-2 infected hamsters at 4 RTV + ALG-097111 (200 mg/kg/dose, BID, SC) + rit
Slide 45: 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 – CHB › STOPS molecule (ALG-010133) Phase 1 clinical trial ongoing, dosing in CHB patients › CAM (ALG-000184) Phase 1 clinical tri
Slide 46: Aligos Therapeutics
ALIGOS THERAPEUTICS
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