Aligos Therapeutics, Inc. · NASDAQ:ALGS
Aligos Therapeutics — Jefferies Healthcare Conference 2020
33 slides from Aligos Therapeutics's conference presentation, Jun 4, 2020
Slide 1: Jefferies Healthcare Conference
Lawrence M. Blatt, Ph.D. CEO & Co-Founder Jefferies Healthcare Conference June 4, 2020
Slide 2: Aligos Therapeutics Mission
Aligos Therapeutics Mission Chronic Hepatitis B Virus (HBV) COVID-19 (Broad Spectrum CoV) Lipotoxicity - NAFLD, NASH Infection • Oligonucleotide approaches • THR-β agonist • Capsid Assembly Modulator • Small molecules (CAM) IP licensed from Emory University (Schinazi Laboratory) • Oligonucleotides (
Slide 3: Senior Leadership Team
Senior Leadership Team Lawrence Blatt Leonid Beigelman Julian Symons, EVP Lucinda Quan, EVP John Fry, EVP Chief Executive Officer President Chief Scientific Officer Chief Business Officer Head Clinical Development Janssen, Alios, InterMune Janssen, Alios, InterMune Janssen, Alios, Roche Merck, Janss
Slide 4: Aligos Pipeline at a Glance
Aligos Pipeline at a Glance Candidate Indication MOA Discovery Preclinical and Clinical Development Phase 1 Phase 2 ALG-010133 Chronic Hepatitis B STOPS™ ALG-000184 Chronic Hepatitis B CAM ALG-020572 Chronic Hepatitis B ASO ALG-020576 Discovery Coronavirus Various Discovery Liver Diseases Various 4
Slide 5: Coronavirus
ALIGOS THERAPEUTICS Coronavirus
Slide 6: Preferred Features of Antivirals for Coronavirus
Preferred Features of Antivirals for Coronavirus • Broadly active against diverse coronaviruses • High barrier to resistance Average 5-day incubation period Range 2-14 days • Extended therapeutic window compatible with prophylaxis and Relative Frequency treatment • Combination therapy preferred to p
Slide 7: Approach to Developing a Pan-Coronavirus Treatment
Approach to Developing a Pan-Coronavirus Treatment • Leverage Aligos’ virology expertise to develop purpose-built drugs with diverse MOAs – Oligonucleotides (ASO, siRNA and aptamers) › Targeting conserved gene sequences – Nucleoside and nucleotide analogs › Broadly active against all coronavirus pol
Slide 8: Chronic Hepatitis B
ALIGOS THERAPEUTICS Chronic Hepatitis B
Slide 9: Chronic Hepatitis B Combination Treatment Strategy
Chronic Hepatitis B Combination Treatment Strategy • Current nucleos(t)ide analog treatment is lifelong and rarely leads to functional cure – Functional cure* › Sustained, undetectable HBsAg and HBV DNA in serum with or without seroconversion to hepatitis B surface antibody (anti-HBs) after completi
Slide 10: S-antigen Transport-inhibiting Oligonucleotide Polymers (STOPS)
S-antigen Transport-inhibiting Oligonucleotide Polymers (STOPS™) Oligonucleotide aptamers (protein binding), comprised of a repeating poly AC sequence 10
Slide 11: Poly AC Oligonucleotides Have Clinical Validation
Poly AC Oligonucleotides Have Clinical Validation: Treatment Results in Multiple log10 Reductions of HBsAg and Functional Cure 500 mg Q-weekly: IV administration 250 mg Q-weekly: IV administration Multiple log 10 reductions Reported a 39% functional cure REP 102: REP2139 Mono Therapy REP 401: REP213
Slide 12: Aligos Approach to STOPS for Chronic Hepatitis B
Aligos Approach to STOPS for Chronic Hepatitis B • Thoroughly explored chemistry around STOPS structure – Optimized for potency, dose frequency and subcutaneous delivery Live Infection HepG2.2.15 ^ Aligos Traditional Novel Aligos Novel 2’OME Linkage ALG # Novel Linkage EC50 nM CC50 nM EC50 nM CC50 n
Slide 13: ALG-010133 Demonstrates >100-fold Potency vs. Reference
ALG-010133 Demonstrates >100-fold Potency vs. Reference HBsAg (HepG2.2.15) ALG-010133 100 ALG-010004 75 % of inhibition 50 25 0 -25 1 10 100 1000 10000 Conc. nM PBMC Live HBV / HepG2-NTCP HepG2.2.15 Structure Activation EC50 nM CC50 nM EC50 nM CC50 nM REP 2139 (AC)20 (Reference)* [2’-OMe-A, 2’-OMe-5
Slide 14: ALG-010133: NHP Multiple Dose Exposure in Liver
ALG-010133: NHP Multiple Dose Exposure in Liver Supports Weekly Subcutaneous Delivery • Much higher liver exposure observed for SC compared to IV dosing in NHPs • High and dose proportional exposure in liver following three weekly SC doses 100,000 [ALG-010133] (ng/g) 80,000 Monkey Liver 60,000 Data
Slide 15: Aligos STOPS Summary
Aligos STOPS Summary • Chemistry of STOPS has been thoroughly explored • Multiple proprietary STOPS with 10-200-fold enhanced in vitro potency over REP-2139 in several HBV cell models identified • ALG-010133 has been selected as the lead candidate – Scale-up completed to enable initiation of toxicol
Slide 16: Capsid Assembly Modulators (CAMs)
Capsid Assembly Modulators (CAMs) 16
Slide 17: CAMs Have Demonstrated Clinical Anti-HBV Activity
CAMs Have Demonstrated Clinical Anti-HBV Activity JNJ-6379 Phase 1b Data in HBV-infected Individuals -0.04 (0.28) -2.16 (0.49) **** * -2.70 (0.53) Each * refers to one patient with HBV *** *** *** -2.89 (0.48) DNA <LLOQ of the HBV DNA assay‡ • Unlike nucleoside analogues, drops in HBV RNA were also
Slide 18: Aligos Class-II CAMs Demonstrate Best-In-Class Potency
Aligos Class-II CAMs Demonstrate Best-In-Class Potency ALG-001075 Janssen Assembly Arbutus* Janssen Assembly Arbutus* Enanta Assembly (Advancing Compound JNJ-6379 ABI-H0731 AB-423 JNJ-0440 ABI-H2158 AB-506 EDP-514 ABI-H3733 as prodrug ALG-000184) Current Completed Completed Phase 2a Phase 2a Phase 1
Slide 19: ALG-001075 5-Log10 Drop in HBV DNA in AAV-HBV Mouse Model
ALG-001075 5-Log10 IU/mL Drop in HBV DNA in the AAV-HBV Mouse Model Serum HBV-DNA 56-day study, all compounds dosed PO LLOD 50% (3/6) of animals below lower limit of detection (LLOD; 2 log10 IU/mL HBV DNA) • Dose dependent reduction in HBV DNA observed in all treatment groups • No changes in HBsAg l
Slide 20: Aligos Capsid Assembly Modulator Summary
Aligos Capsid Assembly Modulator Summary • ALG-000184, a prodrug of ALG-001075, selected as lead candidate – Dose range finding studies completed in rat and dog with ALG-000184 – GLP toxicology studies to support first in human studies are ongoing – Regulatory filing planned Q3 2020 › On-track to be
Slide 21: Antisense Oligonucleotides (ASO)
Antisense Oligonucleotides (ASO) 21
Slide 22: Small-Interfering RNAs vs. Antisense Oligonucleotides
Small-Interfering RNAs vs. Antisense Oligonucleotides Lennox, KA & Behlke, MA J Rare Dis Res Treat (2016) 1(3): 66-70 22
Slide 23: Aligos' Unique Two-Trigger ASO Strategy for CHB
Aligos’ Unique Two-Trigger ASO Strategy for CHB • Single-trigger: Roche, GSK (Ionis), Dicerna, Vir (Alnylam), Arbutus • Two-trigger: Aligos’ ASO strategy uses both S and X triggers – Benefits of the two-trigger strategy › Increased resistance barrier, better coverage of genotypes & integrated genome
Slide 24: ALG-020572 Selected as S-trigger Candidate
ALG-020572 Selected as S-trigger Candidate AAV-HBV Mouse Model: Excellent Efficacy without ALT Elevation 24
Slide 25: ALG-020576 Selected as X-trigger Candidate
ALG-020576 Selected as X-trigger Candidate AAV-HBV Mouse Model: Excellent Efficacy without ALT Elevation Change in HBsAg Serum ALT Mean ± SEM Mean ± SEM G 01: Vehicle, 5x, SC, Q3D G 01: Vehicle, 5X, SC, Q3D G 02: Roche SSO-2, 5x10 mg/kg, SC, Q3D G 02: Roche SSO-2, 5x10 mg/kg, SC, Q3D G 06: ALG-02057
Slide 26: ALG-020572 (S) and ALG-020576 (X) in 1:1 Combination
ALG-020572 (S) and ALG-020576 (X) in 1:1 Combination Demonstrated Enhanced Potency over GSK836 Serum HBsAg Mean ± SEM G 01: Vehicle, 5 mL/kg, SC, 6 doses G 09: ALG-020572-3 + ALG-020576-2 (1:1), 6x10 mg/kg, SC, G 10: ALG-020572-3 + ALG-020576-2 (1:1), 6x3 mg/kg, SC, G 15: ALG-020001-2, 6x10 mg/kg, S
Slide 27: Aligos Antisense Oligonucleotide Summary
Aligos Antisense Oligonucleotide Summary • Aligos is pursuing a two-trigger ASO strategy – Bioinformatics applied using >8000 available HBV sequences – Two triggers provide a higher resistance barrier and better genome coverage • X and S triggers selected, ALG-020572 and ALG-020576 – These incorpora
Slide 28: Hepatitis B Virus Clinical Development Combination Strategy
Hepatitis B Virus Clinical Development Combination Strategy 28
Slide 29: Value Creation in Phase 1 - Establish POC in Monotherapy
Value Creation in Phase 1 - Establish POC in Monotherapy • Phase 1 studies (monotherapy) CAM SAD/MAD CHB Patients in HV x 28 days – Establish safety – Determine dose and schedule STOPS SAD/MAD CHB Patients in HV x 12 weeks • CAM – HBV DNA and RNA reductions ASO SAD/MAD CHB Patients in HV x 12 weeks
Slide 30: Phase 2 and Phase 3 - Establish Value of Combinations
Phase 2 and Phase 3 - Establish Value of Combinations • Unique ability to explore multiple Combination Protocol validated agents in Multiple combinations of combination therapy CAM, STOPS and ASO +/- SOC Pivotal Trial(s) in patients with CHB x 24-48 weeks treatment • Achievement of functional cure S
Slide 31: Aligos Clinical Development Pipeline
CTA Approval Aligos Clinical Development Pipeline POE & POC Data Readouts Conference Presentations 2019 2020 2021 2022 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Preclinical Dose Range Finding 28-day GLP Toxicology (PO) Phase 1a Phase 1b HBV CAM Scale-Up Toxicology SAD / MAD in MAD in Patients HV ALG-00
Slide 32: Aligos Therapeutics Summary
Aligos Therapeutics Summary • Assembled a world-class team with a proven track record of success • Substantial Angel, Series A and B funding completed • License agreement with Emory University for HBV lead asset executed • License agreement executed for 3rd generation oligonucleotide chemistry • Res
Slide 33: Aligos Therapeutics
ALIGOS THERAPEUTICS
Aligos Therapeutics — Jefferies Healthcare Conference 2020 on 6ix