Arbutus Biopharma Corporation · NASDAQ:ABUS
Arbutus Biopharma — Investor Presentation (May 2019)
17 slides from Arbutus Biopharma's investor presentation, May 20, 2019
Slide 1: Investment Highlights
Investment Highlights Singular therapeutic focus - curing chronic Hepatitis B Virus (HBV) Team with antiviral expertise & proven track record Genevant liberates value from delivery technology Strong Financial Position Robust HBV Portfolio Significant unmet medical need in HBV Applying knowledge gain
Slide 2: Proven Leadership Team
Proven Leadership Team Mark J. Murray, PhD Gaston Picchio, PhD Chief Development Officer President & CEO Successful track records in both the discovery and development of multiple antivirals: sofosbuvir, etravirine, rilpivirine, telaprevir and simeprevir David C. Hastings Chief Financial Officer Mic
Slide 3: HBV Lifecycle Illustrates Key Points for Intervention
HBV Lifecycle Illustrates Key Points for Intervention A combination of agents with complementary MOA is needed to cure HBV 1 – NA 2 – AB-506 3 – AB-729 3 – RNA destabilizer 2 3 1 2 NASDAQ: ABUS www.arbutusbio.com
Slide 4: Keys to Therapeutic Success
Keys to Therapeutic Success Reduce/Suppress Viral DNA & Antigens 1 Block Replication NA Capsid Inhibitor RNAi Block HBsAg RNAi RNA Destabilizer Address cccDNA Suppress HBV DNA and viral antigens Capsid Inhibitor cccDNA inhibitor Leading to an Reawaken host immune response Therapeutic success will re
Slide 5: Arbutus HBV Pipeline
Arbutus HBV Pipeline Lead Op Phase I Development IND Enabling HV HBV Phase II HBV DNA Suppression AB-506 Capsid Inhibitors 3rd gen HBsAg Reduction RNAi AB-729 AB-452 RNA Destabilizers 2nd Gen Immune Reawakening PD-L1 1st gen cccDNA 1st gen 7 NASDAQ: ABUS www.arbutusbio.com
Slide 6: Capsid Inhibitor: Blocking HBV Replication
Capsid Inhibitor: Blocking HBV Replication Reduce Viral DNA & Antigens HBV Replication cccDNA Formation Driving HBV DNA to undetectable, in the serum and in the liver is a key to therapeutic success in HBV Reduced HBsAg Immuno-modulation Reawaken Immune Response NASDAQ: ABUS www.arbutusbio.com 8
Slide 7: AB-506 – Capsid Inhibitor
AB-506 – Capsid Inhibitor AB-506 shows preclinical potency and PK profile consistent with best in class agents Active against all genotypes & NA resistant variants Once daily dosing Complementary with HBsAg reducing agents AB-506 Potently Reduces HBV DNA in Serum and Inhibits Liver HBV DNA more than
Slide 8: Driving Down HBsAg Is A Key to Therapeutic Success in HBV
Driving Down HBsAg Is A Key to Therapeutic Success in HBV Reduce/Suppress Viral DNA & Antigens HBV Replication HBsAg cccDNA Formation • HBsAg is responsible for immune exhaustion Replication inhibitors do not block HBsAg production Reduced HBsAg • Immunotherapy Reawaken/Boost Immune Response NASDAQ:
Slide 9: AB-729 RNAi Therapeutic
AB-729 RNAi Therapeutic Single trigger RNAi agent targeting all HBV transcripts Inhibits HBV replication and lowers all HBV antigens Potent HBsAg reduction in preclinical models Pan-genotypic activity across HBV genotypes Proprietary GalNAc-conjugate delivery technology provides liver targeting and
Slide 10: AB-729 In Vivo Single Dose Response & Duration
AB-729 In Vivo Single Dose Response & Duration Clear dose response in AAV mouse model 4 3 Saline 1 mg/kg 3 mg/kg 9 mg/kg 2 Mean (n=5) ± SD 1 Achieves maximum HBsAg reduction possible in this model 0 LLOQ -1 Duration supports a clinical dosing frequency of once per month 0 2 4 6 8 10 1 dose siRNA Wee
Slide 11: Small Molecule HBV RNA Destabilizers
Small Molecule HBV RNA HBV RNA reduction leads to interference in viral gene expression, DNA replication, and virion assembly Destabilizers AAV mouse model PO dosing 1 0 0 1 0 Dose-dependent reduction in HBsAg 1 0 1 2 3 S t u d y 4 D a y 5 6 7 HBsAg reduction correlates with reductions in liver HBV
Slide 12: AB-452 and RNA Destabilizer Program
AB-452 and RNA Destabilizer Program Multiple evaluations underway to support AB-452 and RNA destabilizer program next steps Multiple small molecule chemotypes under investigation to maximize program opportunity Completed Ongoing IND enabling studies and 28 day toxicology AB-452 mechanism of action s
Slide 13: Preclinical Combination In Humanized Mouse Model
Preclinical Combination In Humanized Mouse Model RNAi + Capsid inhibitor containing regimens result in HBV DNA and HBsAg reductions Serum HBsAg Serum HBV DNA Treatment for 6 weeks Dosage Route Frequency Capsid Inhibitor 8 100 mg/kg PO BID 3 ETV 1.2 µg/kg PO QD 7 PegIFN 30 µg/kg SQ 2×/wk RNAi 3 mg/kg
Slide 14: Drug Combination Analysis
Drug Combination Analysis Capsid Inhibitor + Antigen Inhibitor of AB-506 + AB-729 50 Moderate Synergy Strong Synergy Minor Synergy HBV-infected primary human hepatocytes Interpretive guidelines as per Prichard & Shipman 1990 NASDAQ: ABUS www.arbutusbio.com 16 Assayed Marker Inhibitor A Inhibitor A E
Slide 15: Potential Path to a Combination HBV Cure
Potential Path to a Combination HBV Cure Drive to undetectable HBV DNA and HBsAg 2019 2020 2021 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Multi-dosing HBV cohorts AB-506* Capsid inhibitor * Start dates approximate Phase 2 Long term safety / efficacy 506 + NA Safety / Efficacy - HV / HBV Pts AB-729 * GalNac-RNAi
Slide 16: Key Catalysts for 2019 - 2020
Key Catalysts for 2019 - 2020 AB-729 AB-729 +AB-Top line dose HBV data w/ NA in HBV HBV data study www.arbutusbio.com 2H 2019 2020 AB-729AB-506AB-506AB-506 InitiationTop lineAdditionalCTA filing to of PhasePhasemulti-dosingInitiate 1 study1a/1b datacohortsPhase 2 NASDAQ: ABUS AB-729Combo Study Singl
Slide 17: Key Catalysts for 2019 - 2020
Key Catalysts for 2019 - 2020 AB-729 Initiation of Phase 1study BIOPHARMA 2H 2019 AB-506 AB-506 Topline Additional Phase multi-dosing 1a/1b data cohorts AB-506 filingto Initiate Phase 2 dy AB-729 Topline Single-dose HBV data 2020 AB-729 Top line multi- dose HBV data Combo Study AB-729 +AB- 506 w/ NA