Arbutus Biopharma Corporation · NASDAQ:ABUS
Arbutus Biopharma — Investor Presentation (August 2019)
18 slides from Arbutus Biopharma's investor presentation, Aug 9, 2019
Slide 1: Forward-Looking Statements
Forward-Looking Statements 2 This presentation contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and Canadian securities laws. All statements that are not historical facts are hereby identified as forward-looking statements for this p
Slide 2: Investment Highlights
Investment Highlights Singular therapeutic focus - curing chronic Hepatitis B Virus (HBV) 3 Significant unmet medical need in HBV Team with antiviral expertise & proven track record Robust HBV Portfolio AB-506 + AB-729 w/ NA in HBV pts Expected 2H 2020 Applying knowledge gained from HIV and HCV succ
Slide 3: Proven Leadership Team
NASDAQ: ABUS www.arbutusbio.com 4 Proven Leadership Team Successful track records in both the discovery, development, and commercialization of multiple antivirals: sofosbuvir, etravirine, rilpivirine, telaprevir and simeprevir William H. Collier Chief Development Officer Chief Financial Officer Pres
Slide 4: HBV Lifecycle Illustrates Key Points for Intervention
3 2 1 2 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 NASDAQ: ABUS www.arbutusbio.com
Slide 5: Keys to Therapeutic Success
Block Replication NA Capsid Inhibitor RNAi Block HBsAg RNAi RNA Destabilizer Address cccDNA Capsid Inhibitor cccDNA inhibitor Reactivate by HBsAg Reduction RNAi RNA Destabilizer Activate PD-L1 antagonist PegIFN Leading to an HBV CURE Keys to Therapeutic Success 6 MOA: Mechanism Of Action NA: Nucleos
Slide 6: Arbutus HBV Pipeline
Arbutus HBV Pipeline 7 Phase I Lead Op Development IND Enabling Healthy Subjects HBV Subjects Phase II HBV DNA Suppression Capsid Inhibitors AB-506 3rd gen HBsAg Reduction RNAi AB-729 HBV RNA Destabilizers AB-452 2nd Gen Immune Reawakening PD-L1 1st gen cccDNA 1st gen
Slide 7: Capsid Inhibitor: Blocking HBV Replication
8 Driving HBV DNA to undetectable, in the serum and in the liver is a key to therapeutic success in HBV Capsid Inhibitor: Blocking HBV Replication Reduce Viral DNA & Antigens Reawaken Immune Response HBV Replication cccDNA Formation Reduced HBsAg Immuno-modulation
Slide 8: AB-506 Capsid Inhibitor
AB-506 Capsid Inhibitor AB-506 shows preclinical and clinical potency and PK profile consistent with best in class agents 9 Active against all genotypes & NA resistant variants Once daily dosing Complementary with HBsAg reducing agents PK: Pharmacokinetics CHB: Chronic Hepatitis B Clinical Developme
Slide 9: AB-506 Capsid Inhibitor Clinical Development Next Steps
AB-506 Capsid Inhibitor Clinical Development Next Steps 10 Phase 1a healthy subject study investigating dosing of AB-506 for 28 days Results expected later this year Continue with Phase 1b study in CHB subjects investigating longer dosing of AB-506 Establish longer term safety (with and w/o NA) Incl
Slide 10: Driving Down HBsAg Is A Key to Therapeutic Success in HBV
Driving Down HBsAg Is A Key to Therapeutic Success in HBV 11 HBsAg is responsible for immune exhaustion Replication inhibitors do not block HBsAg production Reduce/Suppress Viral DNA & Antigens Reawaken/Boost Immune Response Reduced HBsAg Immunotherapy HBV Replication HBsAg cccDNA Formation
Slide 11: AB-729 RNAi Therapeutic
AB-729 RNAi Therapeutic Polymerase, Core Ag, e Ag, pgRNA sAg sAg HBx 12 Proprietary GalNAc-conjugate delivery technology provides liver targeting and enables subcutaneous dosing Single trigger RNAi agent targeting all HBV transcripts Inhibits HBV replication and lowers all HBV antigens Potent HBsAg
Slide 12: AB-729 In Vivo Single Dose Response & Duration
AB-729 In Vivo Single Dose Response & Duration Clear dose response in AAV mouse model Achieves maximum HBsAg reduction possible in this model Duration supports a clinical dosing frequency of once per month 13 Mean (n=5) ± SD 0 2 4 6 8 10 -1 0 1 2 3 4 Weeks After One SC Dose 1 mg/kg 3 mg/kg 9 mg/kg L
Slide 13: Small Molecule HBV RNA Destabilizers
Small Molecule HBV RNA Destabilizers HBV RNA reduction leads to interference in viral gene expression, DNA replication, and virion assembly AAV mouse model PO dosing Dose-dependent reduction in HBsAg HBsAg reduction correlates with reductions in liver HBV RNAs 14 Gotchev, D., et al., AASLD, 2017, Ab
Slide 14: AB-452 and RNA Destabilizer Program
Multiple small molecule chemotypes under investigation to maximize program opportunity AB-452 and RNA Destabilizer Program Completed IND enabling studies and 28 day toxicology AB-452 mechanism of action studies demonstrating AB-452 causes HBV mRNA poly A tail shortening Host protein knock out causes
Slide 15: Preclinical Combination In Humanized Mouse Model
Preclinical Combination In Humanized Mouse Model RNAi + Capsid inhibitor containing regimens result in HBV DNA and HBsAg reductions 16 Treatment for 6 weeks Dosage Route Frequency Capsid Inhibitor 100 mg/kg PO BID ETV 1.2 µg/kg PO QD PegIFN 30 µg/kg SQ 2×/wk RNAi 3 mg/kg IV biweekly Serum HBsAg Seru
Slide 16: Drug Combination Analysis of AB-506 + AB-729
Drug Combination Analysis of AB-506 + AB-729 Capsid Inhibitor + Antigen Inhibitor Assayed Marker Inhibitor A Inhibitor A EC50 AB-729 EC50 (µg/mL) Synergy Volume (%) Antagonism Volume (%) Conclusion HBV-DNA TAF (µM) 0.08 <0.12 88.42, 2.46 -1.1, -2.33 Additive to Moderate Synergy HBsAg 4.12 <0.12 0, 0
Slide 17: Key Catalysts for 2H 2019 - 2020
Key Catalysts for 2H 2019 - 2020 18 2H 2019 2020 AB-729 Preliminary Phase 1a/1b data AB-506 Preliminary Phase 1a/1b data AB-506 28 day healthy volunteer study results AB-506 Final Phase 1b data AB-729 Initiation of Phase 1 study Combination Proof-of-Concept Clinical Trial AB-729 + AB-506 w/ NA in HB
Slide 18: Key Catalysts for 2H 2019 - 2020
Key Catalysts for 2H 2019 - 2020 2H 2019 AB-729 AB-506 ‘AB-506 28 day healthy volunteer Initiation Preliminary “Arbutus AB-729 Preliminary 2020 AB-506 Final Phase 1b data Combination Proof-of- Concept Glinical Trial AB-729+ AB-5S06 w/NAin HBV pts
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