Aligos Therapeutics, Inc. · NASDAQ:ALGS
Aligos Therapeutics — Investor Presentation (November 2021)
49 slides from Aligos Therapeutics's investor presentation, Nov 18, 2021
Slide 1: Corporate Deck
Lawrence M. Blatt, Ph.D. Chairman, CEO & Co-Founder C Corporate Deck November 18th, 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 GOALS 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: Aligos Development Portfolio: Multiple Data Readouts Planned Throughout 2022
Aligos Development Portfolio Multiple Data Readouts Planned Throughout 2022 Candidate Indication MOA Clinical Trial Timelines* & Data Readouts Ongoing enrollment + dosing x 12 wks in multiple CHB cohorts ALG-010133 CHB STOPSTM Topline Data Available (HBsAg, Safety) CHB Cohorts 1-3 Dosing x 28 days i
Slide 5: Chronic Hepatitis B
ALIGOS THERAPEUTICS Chronic Hepatitis B
Slide 6: 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 7: Chronic Hepatitis B and Functional Cure (FC)
Chronic Hepatitis B and Functional Cure (FC) 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 (undetec
Slide 8: 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 9: STOPS
STOPS ALG-010133, a novel, chemically optimized poly-AC oligonucleotide analog 8
Slide 10: 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 › NAPs = Nucleic
Slide 11: ALG-010133 Lead STOPS Molecule
ALG-010133 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 Proprietary chemistry, extensive structure activity relationship (SAR) effort identified STOPS ~100-fold improvement in potency vs. NAPs
Slide 12: 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 13: 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 14: 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 • Similar to ISR rate for other oligonucleotides (ASO,
Slide 15: Significant HBsAg Reductions with Monotherapy
Poly AC Oligonucleotides Have Clinical Validation Significant HBsAg Reductions with Monotherapy • Phase 1 NAP study (REP 102) REP 102 Study (HBeAg+)* – REP 2139-Ca (IV) monotherapy x ≥20 weeks in treatment naïve, HBeAg positive subjects › High baseline HBsAg levels – Highly variable HBsAg reductions
Slide 16: Significant HBsAg Reductions with Monotherapy
Poly AC Oligonucleotides Have Clinical Validation Significant HBsAg Reductions with Monotherapy • Phase 1 NAP study (REP 102) REP 102 Study (HBeAg+)* – REP 2139-Ca (IV) monotherapy x ≥20 weeks in treatment naïve, HBeAg positive subjects › High baseline HBsAg levels – Highly variable HBsAg reductions
Slide 17: ALG-010133 Phase 1b Study in CHB Subjects
ALG-010133 Phase 1b Study in CHB Subjects Multiple Doses in CHB Subjects NA Suppressed (DNA < LLOQ), HBeAg neg or pos, HBsAg >100 IU/mL Up to 6 cohorts (n=10 per Cohort; n=8 ALG-010133, n=2 Placebo) Up to 12 weekly SC doses Endpoints: PK, safety, antiviral activity (e.g., HBsAg) Endpoint data collec
Slide 18: ALG-010133 Development Timelines
ALG-010133 Development Timelines* Topline Data (HBsAg Dose Response, Safety) ALG-010133 (STOPS) Enrollment, completion of dosing CHB (multiple cohorts) 2021 2022 Q3 Q4 Q1 Q2 Q3 Topline data from Cohorts 1-3 anticipated to be released Q2 2022 *Timelines are approximate and subject to change based on
Slide 19: CAM
CAM ALG-000184, a prodrug of ALG-001075 18
Slide 20: Class-II CAMs Have Clinical Validation
Class-II CAMs Have Clinical Validation JNJ-6379* JNJ-440* ABI-731 At Day 28 Class-II CAMs at Day 28: ~2.5-3 log10 IU/mL DNA reductions; ≤56% with DNA < LLOQ Zoulim et al., AASLD 2018 *~75% of subjects are HBeAg negative Gane et al., AASLD 2019 Yuen, AASLD 2018 19
Slide 21: 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 22: 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 23: 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 or Positive 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)
Slide 24: ALG-000184 CHB Safety (100, 50 mg cohorts)
ALG-000184 CHB Safety (100, 50 mg cohorts) • Safety – Serious adverse events: 1 (unrelated) › Subject with a history of sciatica experienced mild back pain resulting in brief hospitalization for pain management – TEAEs › Leading to discontinuation: none › Generally mild or moderate › Four subjects (
Slide 25: ALG-000184 CHB PK (100, 50 mg cohorts)
ALG-000184 CHB PK (100, 50 mg cohorts) PK over 28 days: exposures increased dose proportionally; low-moderate variability; minimal accumulation Gane et. al., AASLD 2021. 24
Slide 26: ALG-000184 Day 28 Antiviral Activity Data
ALG-000184 (100, 50 mg) Day 28 Antiviral Activity* Data DNA RNA Mean (SD) Reduction Mean (SD) Reduction Placebo: 0.1 (0.1) Placebo: 0.1 (0.1) 50 mg: 3.8 (0.2) 50 mg: 1.9 (0.4) 100 mg: 3.2 (0.1) 100 mg: 1.6 (0.3) 50 mg, 100 mg ALG-000184 x 28 days Similar rapid, deep declines in HBV DNA, RNA levels S
Slide 27: ALG-000184 Development Timelines
ALG-000184 Development Timelines* AASLD Poster EASL/APASL Presentation (HBV DNA/RNA Dose Response, Safety) ALG-000184 Enrollment, completion of dosing CHB (CAM) (multiple cohorts) 2021 2022 Q3 Q4 Q1 Q2 Q3 Topline data targeted for presentation at EASL/APASL (Q2 2022) *Timelines are approximate and s
Slide 28: Additional Oligonucleotide Approaches
Additional Oligonucleotide Approaches • ALG-020572 (ASO) • ALG-125755 (siRNA) 27
Slide 29: Antisense Oligonucleotides and Small-Interfering RNAs
Antisense Oligonucleotides and Small-Interfering RNAs RNA interference (RNAi) Antisense oligonucleotides (ASOs) All PS* Wings (LNA) GAP (DNA) Aligos is agnostic to oligonucleotide modality *PS = Phosphorothioate Lennox, KA & Behlke, MA J Rare Dis Res Treat (2016) 1(3): 66-70. 28
Slide 30: 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 31: ALG-020572 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 30
Slide 32: ALG-020572 vs. GSK-3228836 ASO in the AAV-HBV Mouse Model
ALG-020572 Our ASO vs. GSK-3228836 ASO in the AAV-HBV Mouse Model Serum HBsAg Vehicle, SC, 6 doses ALG-020001 (GSK-3228836), 3 mg/kg, SC, 6 doses ALG-020001 (GSK-3228836), 10 mg/kg, SC, 6 doses ALG-020572, 3 mg/kg, SC, 6 doses ALG-020572, 10 mg/kg, SC, 6 doses ALG-020572 demonstrates significantly i
Slide 33: 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 Trial is ongoing – currently dosing in HV Phase 1 target mean HBsAg reduction
Slide 34: ALG-020572 Development Timelines
ALG-020572 Development Timelines* Initiation of Phase 1 (Regulatory Filing) ALG-020572 Phase 1-enabling Nonclinical SAD in HV Multiple dosing CHB (ASO) Studies 2021 2022 Q2 Q3 Q4 Q1 Q2 Dosing in healthy volunteers initiated, dosing in CHB subjects (MAD) anticipated in Q1 2022 SAD – Single ascending
Slide 35: 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 36: ALG-125755 vs. VIR-2218 siRNA in the AAV-HBV Mouse Model
ALG-125755 Our siRNA vs. VIR-2218 siRNA in the AAV-HBV Mouse Model HBsAg in Serum ALG-125755 demonstrates significantly improved efficacy in vivo vs. a competitor siRNA 35
Slide 37: 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 38: ALG-125755 + ALG-020572 In Vivo Combination Study
ALG-125755 + ALG-020572 In Vivo Combination Study in the Mouse AAV-HBV Model HBsAg in Serum 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 The combination of our siRNA and ASO delivers
Slide 39: NASH
NASH ALG-055009, small molecule THR-β agonist 38
Slide 40: 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 41: 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 42: ALG-055009 Development Timelines
ALG-055009 Development Timelines* Initiation of Phase 1 (Regulatory filing) 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-correc
Slide 43: 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 44: Coronavirus
ALIGOS THERAPEUTICS Coronavirus
Slide 45: 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 46: 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 47: Aligos Development Portfolio: Multiple Data Readouts Planned Throughout 2022
Aligos Development Portfolio Multiple Data Readouts Planned Throughout 2022 Candidate Indication MOA Clinical Trial Timelines* & Data Readouts Ongoing enrollment + dosing x 12 wks in multiple CHB cohorts ALG-010133 CHB STOPSTM Topline Data Available (HBsAg, Safety) CHB Cohorts 1-3 Dosing x 28 days i
Slide 48: 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 (200, 400 mg) • Topline data
Slide 49: Aligos Therapeutics
ALIGOS THERAPEUTICS
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