Aligos Therapeutics, Inc. · NASDAQ:ALGS
Aligos Therapeutics — Investor Presentation (August 2021)
54 slides from Aligos Therapeutics's investor presentation, August 2021
Slide 1: Corporate Presentation August 2021
Lawrence M. Blatt, Ph.D. Chairman, CEO & Co-Founder C Corporate Presentation August 2021
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 Therapeutics Highlights
Aligos Therapeutics Highlights OUR OUR OUR OUR OUR MISSION PLATFORM STRATEGY TEAM GOAL Develop novel Oligonucleotides Develop Decades of drug Become a world therapeutics to pharmacologically discovery and leader in antiviral address unmet Small molecules optimized drug development therapies for CHB
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 Intellectual Property AM Chemicals Chemistry, Manufacturing Proprietary GalNAc and Controls Merck (MSD) NASH Collabo
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 • First in class entrants – Demonstrated mechanistic proof of principle – Several did not gain approval due to poor pharmacology • Late entrants with improved pharmacology attained signifi
Slide 6: Our Pipeline
Our Pipeline Anticipated Candidate Indication MOA Discovery Nonclinical Phase 1 Phase 2 Phase 3 Milestones Initial ALG-010133 CHB STOPSTM Phase 1 Data Initial ALG-000184 CHB CAM Phase 1 Data Phase 1 ALG-020572 CHB ASO Start in 2H 2021 Phase 1 ALG-125755 CHB siRNA Start in 1H 2022 Phase 1 ALG-055009
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 the world – >290 million carriers worldwide (2020) – Affects ~8 million in US, EU, Japan (2015) – Responsible for ~900,000 deaths/year (2015) – Only ~2% of patients currently treated (2016) • Our Portfolio
Slide 9: Chronic Hepatitis B and Functional Cure
Chronic Hepatitis B and 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 (STOPS = S-antigen Transport inhibiting Oligonucleotide Polymers) 10
Slide 12: Poly AC Oligonucleotides Have Clinical Validation
Poly AC Oligonucleotides Have Clinical Validation Functional Cures Observed in Combination Studies HBsAg Levels in REP 401 Study • Replicor 401 Study (Figure*) TDF TDF+pegIFN TDF + pegIFN + NAP – Treatment naïve, HBeAg negative TDF TDF + pegIFN + NAP – NAP REP 2139-Mg or REP 2165-Mg › NAP = Nucleic
Slide 13: ALG-010133 Our Lead STOPS Molecule
ALG-010133 Our Lead STOPS Molecule Significantly greater potency* vs. reference Poly-AC oligonucleotide** EC50 = 3.2 nM EC50 = 3.86 nM EC50 = 339.5 nM EC50 = 343.3 nM ~100-Fold improvement in potency enables efficient subcutaneous administration *Hong et. al., AASLD (2019), poster #0689. **ALG-01000
Slide 14: STOPS Mechanism of Action to Inhibit HBsAg Secretion
STOPS Mechanism of Action to Inhibit HBsAg Secretion* • STOPS affinity chromatography identified ~20 cellular binding proteins • Five of these proteins are required for optimal HBsAg production based on siRNA knockdown experiments in HepG2.2.15 cells – SRSF1, HNRNPA2/B1, RPLP2 and RPLP1, GRP78 • All
Slide 15: ALG-010133 Phase 1 Study in HV: Study Design
ALG-010133 Phase 1 Study in HV Study Design 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 MAD Fo
Slide 16: ALG-010133 Phase 1 Study in HV: PK Data
ALG-010133 Phase 1 Study in HV PK Data SAD MAD * Doses ≥125 mg approach linearity; low-to-moderate intersubject variability; no accumulation Doses ≥120 mg anticipated to have antiviral activity *All doses used 100 mg/mL solution except 2nd 200 mg cohort, which used 200 mg/mL solution Gane et. al., E
Slide 17: ALG-010133 Phase 1 Study in HV: Safety
ALG-010133 Phase 1 Study in HV Safety • No serious adverse events (SAEs) • Treatment emergent adverse events (TEAEs) – No TEAEs led to study drug discontinuation – Injection site reactions (ISRs) › Occurred in ~19% of ALG-010133-treated subjects › Generally characterized by localized erythema that w
Slide 18: CHB Studies: Regulatory Guidance for Advancing Antiviral Drugs
CHB Studies Regulatory Guidance for Advancing Antiviral Drugs • Phase 1a – Safety / PK in healthy volunteers • Phase 1b – Safety / PK and biological response (e.g., HBsAg, DNA) in CHB patients. Studies evaluate a range of doses as monotherapy for short durations – Demonstrate biological response – U
Slide 19: Poly AC Oligonucleotides: Significant HBsAg Reductions
Poly AC Oligonucleotides Have Clinical Validation Significant HBsAg Reductions • Phase 1 NAP study (REP 102) REP 102 Study (HBeAg+)* – REP 2139-Ca (IV) monotherapy x ≥20 weeks – Highly variable HBsAg reductions – HBsAg reduction at Week 10** › Ranged from +0.1 to -4.7 log10 IU/mL › Median log10 redu
Slide 20: Poly AC Oligonucleotides: Significant HBsAg Reductions
Poly AC Oligonucleotides Have Clinical Validation Significant HBsAg Reductions • Phase 1 NAP study (REP 102) REP 102 Study (HBeAg+)* – REP 2139-Ca (IV) monotherapy x ≥20 weeks – Highly variable HBsAg reductions – HBsAg reduction at Week 10** › Ranged from +0.1 to -4.7 log10 IU/mL › Median log10 redu
Slide 21: Oligonucleotides HBsAg Reductions Over Time
Oligonucleotides HBsAg Reductions Over Time NAPS ASO siRNA REP 2139 GSK3228836 AB-729 Weekly 500 mg SC doses x 10 weeks 7 doses across 29 days (Days 1,4,8,11,15, 22, 29) AB729 60 60 AB729 mgmg Q4Q4 x 12 weeks x 12 weeks Mean HBsAg reduction: 1.65+2.0 log10 IU/mL Mean HBsAg reduction: 1.6+1.4 (naïve)
Slide 22: Oligonucleotides HBsAg Reductions Over Time
Oligonucleotides HBsAg Reductions Over Time NAPS ASO siRNA REP 2139 GSK3228836 AB-729 Weekly 500 mg SC doses x ≥20 weeks 7 doses across 29 days (Days 1,4,8,11,15, 22, 29) AB729 AB729 60 mg60Q4-12W mg Q4 x 48 12 weeks Mean HBsAg reduction: 3.4+2.3 log10 IU/mL No Data beyond 29 days Mean HBsAg reducti
Slide 23: ALG-010133 Phase 1 Study in CHB Subjects
ALG-010133 Phase 1 Study in CHB Subjects Multiple Doses in CHB Subjects NA Suppressed (DNA < LLOQ), HBeAg neg or pos, HBsAg >1000 IU/mL Up to 6 cohorts (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
Slide 24: CAM
CAM ALG-000184, a prodrug of ALG-001075 23
Slide 25: Class-II CAMs Have Clinical Validation
Class-II CAMs Have Clinical Validation JNJ-6379* JNJ-440* ABI-731 At Day 28 Class-II CAMs result in ~2.5-3 log10 IU/mL reductions in DNA at Day 28 in treatment naïve HBeAg negative CHB patients Zoulim et al., Gastroenterology 2020 *~75% of subjects are HBeAg negative Gane et al., AASLD 2019 Yuen, AA
Slide 26: ALG-000184 Demonstrates ~10 to 300-Fold Improvement in In Vitro Potency
ALG-000184 Demonstrates ~10 to 300-Fold Improvement in In Vitro Potency vs. Other Known CAMs in Clinical Development HBV DNA reduction Compound Current Status Cell Type (EC50 nM) Assembly ABI-H0731 Phase 2 172 AD38 Assembly ABI-H2158 Phase 2 22 AD38 Assembly ABI-H3733 Phase 1 5 AD38 Janssen JNJ-6379
Slide 27: ALG-000184 Phase 1 Study in HVs
ALG-000184 Phase 1 Study in HVs SAD/MAD in HVs 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 doses of 150 and 250 mg Results Safety: all doses well tolerated – no SAEs
Slide 28: 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 Negative 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 da
Slide 29: ALG-000184 CHB Cohort 1 (100 mg) Safety, PK Data
ALG-000184 CHB Cohort 1 (100 mg) Safety, PK Data • Safety – No serious adverse events – No TEAEs leading to discontinuation – All TEAEs were mild except one case of moderate back pain (unlikely related to study drug) › Most common TEAEs: back pain, dry mouth & headache (2 subjects each); nausea (3 s
Slide 30: ALG-000184 CHB Cohort 1 Day 14 Antiviral Activity Data
ALG-000184 CHB Cohort 1 (100 mg) Day 14 Antiviral Activity* Data Antiviral Activity* Mean (SD) Baseline HBV DNA 4.2 (1.0) log10 IU/mL Mean (SEM) HBV DNA reduction: 2.9 (0.2) log10 IU/mL 4 of 8 (50%) ALG-000184-treated subjects <LLOQ 1st cohort (100 mg) has completed dosing, 2nd cohort (50 mg) curren
Slide 31: Additional Oligonucleotide Approaches
Additional Oligonucleotide Approaches • ALG-020572 (ASO) • ALG-125755 (siRNA) 30
Slide 32: Antisense Oligonucleotides and Small-Interfering RNAs
Antisense Oligonucleotides and Small-Interfering RNAs RNA interference (RNAi) Antisense oligonucleotides (ASOs) All PS* Wings (LNA) GAP (DNA) The Aligos team is agnostic to oligonucleotide modality *PS = Phosphorothioate Lennox, KA & Behlke, MA J Rare Dis Res Treat (2016) 1(3): 66-70. 31
Slide 33: Map of HBV Trigger Locations
Map of HBV Trigger Locations ASO ALG-020572 and siRNA ALG-125755 Dicerna Arrowhead (S) Aligos siRNA ALG-125755 (S) Aligos ASO ALG-020572 (S) HBV ASO ALG-020572 (S) and siRNA ALG-125755 (S) trigger locations are >100 nucleotides apart Roche Arrowhead X ASO Arbutus GSK VIR 32
Slide 34: Antisense Oligonucleotide ALG-020572
Antisense Oligonucleotide ALG-020572 Discovery and Advancement of a Differentiated ASO • Antisense oligonucleotides have demonstrated clinical validation in CHB infected patients • We have designed our sequences using our proprietary Luxna Biotech 3rd generation XNA nucleotides to enhance potency, s
Slide 35: ALG-020572 Our ASO Drug Candidate in the AAV-HBV Mouse Model
ALG-020572 Our ASO Drug Candidate in the AAV-HBV Mouse Model Potent in vivo activity of ALG-020572 in the AAV-HBV mouse model without ALT elevation 34
Slide 36: ALG-020572 Our ASO vs. GSK-836 ASO in Mouse Model
ALG-020572 Our ASO vs. GSK-836 ASO in the AAV-HBV Mouse 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 37: ALG-020572 Phase 1a/b Clinical Trial Design
ALG-020572 Phase 1a/b Clinical Trial Design Part 1: SAD (HV) Part 2: VS CHB patients Multiple Cohorts Multiple Cohorts Each Cohort - 6 Active: 2 Placebo Each Cohort - 6 Active: 2 Placebo Loading Doses 1 4 8 11 15 22 29 Day Phase 1 target mean HBsAg reduction: ≥1 log10 IU/mL 36
Slide 38: ALG-020572 Development Timelines
ALG-020572 Development Timelines* Initiation of Phase 1 ALG-020572 Phase 1-enabling SAD in HV Multiple dosing CHB (ASO) Nonclinical Studies 2021 2022 Q2 Q3 Q4 Q1 Q2 Dosing in CHB subjects (MAD) anticipated to start late Q4/early Q1 SAD – Single ascending doses; HV – Healthy volunteers; CHB – Chronic
Slide 39: 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 designed our siRNA sequences using our proprietary technology and liver targeting conjugation to maximize in vitro and in vi
Slide 40: ALG-125755 Our siRNA vs. VIR-2218 siRNA in Mouse Model
ALG-125755 Our siRNA vs. VIR-2218 siRNA in the AAV-HBV Mouse Model HBsAg in Serum Log10 (IU/mL, mean ± SEM) Change in Serum HBsAg Vehicle, 5 mL/kg, SC ALG-125852, 5 mg/kg, SC, Day 0 (VIR-2218) ALG-125755, 5 mg/kg, SC, Day 0 ALG-125755 demonstrates significantly improved efficacy in vivo vs. a compet
Slide 41: ALG-125755 Development Timelines
ALG-125755 Development Timelines* Projected Initiation of Phase 1 ALG-125755 Ph1-enabling Nonclinical Studies SAD in HV (siRNA) 2021 2022 Q3 Q4 Q1 Q2 Q3 Phase 1 target mean HBsAg reduction: ≥1 log10 IU/mL SAD – Single ascending doses; MAD- Multiple ascending doses; HV – Healthy volunteers; CHB – Chr
Slide 42: Aligos' Advancing CHB Portfolio: In Vitro Combination Studies
Aligos’ Advancing CHB Portfolio In Vitro Combination Studies in Cell Based Assays • STOPS ALG-010133 + ASO ALG-020572 (Unconjugated form) – Synergistic (HBsAg) • STOPS ALG-010133 + CAM ALG-000184 (ALG-001075) – Synergistic (HBV DNA) • siRNA ALG-125755 + ASO ALG-020572 (Unconjugated versions) – Syner
Slide 43: ALG-125755 + ALG-020572 In Vivo Combination Study
ALG-125755 + ALG-020572 In Vivo Combination Study 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 dos
Slide 44: NASH
NASH ALG-055009, small molecule THR-β agonist 43
Slide 45: NAFLD and NASH: High Prevalence + No Approved Therapy
NAFLD and NASH* High Prevalence + No Approved Therapy: Large Unmet Need • Disease Progression Metabolic syndrome Liver Inflammation Liver Fibrosis Cirrhosis complications, liver associated with fat (NASH) (cirrhosis) transplant, cancer, death accumulation in liver (NAFLD) • Incidence – NAFLD – 25% w
Slide 46: 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 47: 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 48: ALG-055009 Development Timelines
ALG-055009 Development Timelines* Initiation of Phase 1 ALG-055009 SAD in HV (THR-β) Ph1-enabling Nonclinical Studies MAD in HV with hyperlipidemia 2021 2022 Q1 Q2 Q3 Q4 Q1 Lipid Reduction Target Exceed Madrigal/Viking Phase 1 results at Phase 2b/3 dose levels Mean placebo-corrected LDL-C reduction
Slide 49: 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 2H 2022 • Resmetirom Phase 3 readouts are expected in Q3 2022 • Aligos NASH ALG-055009 program has strong optionality in 2022 – C
Slide 50: Coronavirus
ALIGOS THERAPEUTICS Coronavirus
Slide 51: 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 lack access to, or are opposed to vaccination – Es
Slide 52: ALG-097111 Efficacy in SARS-CoV-2 Hamster Model
ALG-097111 Efficacy in SARS-CoV-2 Hamster Model ✱✱ 7 ✱✱ ALG-097111 SARS-CoV-2 In Vitro Biochemical IC50 = 7 nM Cell-based EC50 =200 nM (A549) 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 gava
Slide 53: 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, currently dosing in 2 CHB cohorts (120, 200 mg) › CAM (ALG-000
Slide 54: Aligos Therapeutics
ALIGOS THERAPEUTICS
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