Aligos Therapeutics, Inc. · NASDAQ:ALGS
Aligos Therapeutics — Investor Presentation (June 2021)
42 slides from Aligos Therapeutics's investor presentation, June 2021
Slide 1: Corporate Presentation June 2021
Lawrence M. Blatt, Ph.D. CEO & Co-Founder C Corporate Presentation June 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 principal – 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 STOPS 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 NA
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) – Only ~2% of patients currently treated (2016) • Our Portfolio – Potentiall
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 10
Slide 12: Poly AC Oligonucleotides Have Clinical Validation
Poly AC Oligonucleotides Have Clinical Validation Significant HBsAg reductions observed with NAPs in treatment naïve CHB subjects REP 102 Study (HBeAg+)* REP 401 Study (HBeAg-)** – Treatment naïve, HBeAg positive – Treatment naïve, HBeAg negative – REP 2139-Ca monotherapy x ≥20 weeks – REP 2139 or 2
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: 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 CHB Subjects NA Suppressed (DNA < LLOQ), HBeAg Negative, HBsAg >1000 IU/mL 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 througho
Slide 16: CAM
CAM ALG-000184, a prodrug of ALG-001075 15
Slide 17: 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 reductions in DNA at Day 28 in treatment naïve HBeAg negative CHB Zoulim et al., Gastroenterology 2020 *~75% of subjects are HBeAg negative Gane et al., AASLD 2019 Yuen, AASLD 2018 16
Slide 18: 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 Phase 1 17
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 HBV DNA > 2000 IU/mL, HBeAg Negative 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 coll
Slide 21: Additional Oligonucleotide Approaches
Additional Oligonucleotide Approaches • ALG-020572 (ASO) • ALG-125755 (siRNA) 20
Slide 22: Antisense Oligonucleotides and Small-Interfering RNAs
Antisense Oligonucleotides and Small-Interfering RNAs All PS > cytoplasm > nucleus, cytoplasm Wings (LNA) GAP (DNA) The Aligos team is agnostic to oligonucleotide modality Lennox, KA & Behlke, MA J Rare Dis Res Treat (2016) 1(3): 66-70. 21
Slide 23: 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 optimized our sequences using our proprietary Luxna Biotech 3rd generation XNA nucleotides to enhance potency,
Slide 24: ALG-020572 Our ASO Drug Candidate 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 23
Slide 25: ALG-020572 Our ASO 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 26: ALG-020572 Development Timelines
ALG-020572 Development Timelines* Initiation of Phase 1 ALG-020572 Ph1-enabling Nonclinical SAD/MAD in HV Multiple dosing CHB (ASO) Studies 2021 2022 Q2 Q3 Q4 Q1 Q2 Ph 1 target HBsAg reduction: ≥1 log10 IU/mL SAD – Single ascending doses; MAD- Multiple ascending doses; HV – Healthy volunteers; CHB –
Slide 27: 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 in v
Slide 28: ALG-125755 siRNA Drug Candidate 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 27
Slide 29: ALG-125755 Our siRNA vs. VIR-2218 siRNA in the Mouse AAV-HBV Model
ALG-125755 Our siRNA vs. VIR-2218 siRNA in the Mouse AAV-HBV Model ALG-125755 demonstrates significantly improved efficacy in vivo vs. a competitor siRNA 28
Slide 30: 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 Ph1 target HBsAg reduction: ≥1 log10 IU/mL SAD – Single ascending doses; MAD- Multiple ascending doses; HV – Healthy volunteers; CHB – Chronic hepa
Slide 31: Aligos' Advancing CHB Portfolio: Combination Studies
Aligos’ Advancing CHB Portfolio Excellent Performance in Combination Studies • STOPS ALG-010133 + ASO ALG-020572 (Unconjugated form) – Strong synergy (HBsAg) • STOPS ALG-010133 + CAM ALG-000184 (ALG-001075) – Minor synergy (HBV DNA) • siRNA ALG-125755 + ASO ALG-020572 (Unconjugated versions) – Minor
Slide 32: NASH
NASH ALG-055009, small molecule THR-β agonist 31
Slide 33: 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 fat accumulation in (NASH) (cirrhosis) transplant, cancer, death liver (NAFLD) • Incidence – NAFLD – 25% worldw
Slide 34: 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 35: 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 36: 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 Ph1 results at Ph2b/3 dose levels Placebo-corrected LDL-C reduction ≥27% SAD – Si
Slide 37: 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 Phase 2b readouts are expected in 2H 2022 • Aligos NASH ALG-055009 program has strong optionality in
Slide 38: Coronavirus
ALIGOS THERAPEUTICS Coronavirus
Slide 39: 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 40: 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 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 – CHB › STOPS molecule (ALG-010133) Phase 1 clinical trial ongoing, dosing in CHB patients › CAM (ALG-000184) Phase 1 clinical tri
Slide 42: Aligos Therapeutics
ALIGOS THERAPEUTICS
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