Benitec Biopharma Inc. · NASDAQ:BNTC

Benitec Biopharma — Investor Presentation (September 2020)

42 slides from Benitec Biopharma's investor presentation, September 2020

  1. Slide 1: Benitec Biopharma Overview

    Benitec Biopharma Overview September 2020 Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 1 www.benitec.com

  2. Slide 2: Safe Harbor Statement

    Safe Harbor Statement This presentation contains "forward-looking statements" within the meaning of section 27A of the US Securities Act of 1933 and section 21E of the US Securities Exchange Act of 1934. Benitec has tried to identify such forward-looking statements by use of such words as "expects,"

  3. Slide 3: Gene Silencing: A Validated Approach to the Treatment of Some Genetic Diseases

    Gene Silencing: A Validated Approach to the Treatment of Some Genetic Diseases • Mutation of a single gene can cause a chronic disease via the resulting intracellular production of a disease- causing protein (i.e. an abnormal form of the protein of interest) • Genetic disorders of this type can ofte

  4. Slide 4: "Silence and Replace": Permanent Gene Silencing and Tissue-Specific Restoration of Biological Function

    “Silence and Replace”: Permanent Gene Silencing and Tissue-Specific Restoration of Biological Function • Our proprietary “Silence and Replace” approach to genetic diseases combines RNAi with gene replacement to drive sustained silencing of disease-causing genes and concomitant replacement with funct

  5. Slide 5: Platform Enables Gene Therapy and Permanent Gene Silencing: DNA-Directed RNA Interference (ddRNAi)

    Platform Enables Gene Therapy and Permanent Gene Silencing: DNA-Directed RNA Interference (ddRNAi) • Combines RNA interference Transient gene silencing - siRNA Permanent gene silencing - ddRNAi with gene therapy delivery • Long-term therapeutic potential from a single administration • Constant, stea

  6. Slide 6: Mechanism of RNA Interference Through the microRNA (miRNA) Pathway

    Mechanism of RNA Interference Through the microRNA (miRNA) Pathway siRNA Versus miRNA Therapeutics Lam et al. Drosha miRNA gene Pri-miRNA Pre-miRNA Transcription • The use of shRNA/miRNA hybrids confers Pol II advantages with respect to expression, safety, Nucleus Exportin 5 and specificity dsRNA Cy

  7. Slide 7: Executive Team: Expertise in Gene Therapy Development, Biological Manufacturing and Capital Allocation

    Executive Team : Expertise in Gene Therapy Development, Biological Manufacturing and Capital Allocation • Jerel Banks, M.D., Ph.D. • Claudia Kloth, Ph.D. – CEO and Executive Chairman – SVP of Manufacturing – Healthcare investment professional with 14 years – Over 20 years of cGMP manufacturing and o

  8. Slide 8: Pipeline: Oculopharyngeal Muscular Dystrophy (OPMD) and Chronic Hepatitis B Virus Infection

    Pipeline: Oculopharyngeal Muscular Dystrophy (OPMD) and Chronic Hepatitis B Virus Infection Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 8 www.benitec.com

  9. Slide 9: Broad Intellectual Property Portfolio

    Broad Intellectual Property Portfolio • OPMD-related intellectual • HBV-related intellectual property: property: – OPMD Family 4 anticipated expiry – HBV Family 3 anticipated expiry May February 2040 2037 – OPMD Family 3 anticipated expiry – HBV Family 2 anticipated expiry May October 2039 2036 – OP

  10. Slide 10: BB-301 for Oculopharyngeal Muscular Dystrophy

    BB-301 for Oculopharyngeal Muscular Dystrophy • LATE-STAGE NON-CLINICAL ASSET WITH CATEGORY-LEADING BIOLOGICAL EFFICACY • GLOBAL PREVALENCE OF OPMD EXCEEDS 15,000 PATIENTS AND COMMERCIAL OPPORTUNITY EXCEEDS $1 BILLION Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 10 www.benitec.

  11. Slide 11: Oculopharyngeal Muscular Dystrophy Lead Candidate BB-301: Product Overview

    Oculopharyngeal Muscular Dystrophy Lead Candidate BB-301: Product Overview • Rare, autosomal dominant, monogenic disease Oculopharyngeal • Estimated prevalence of 15,000 patients in Western countries Muscular Dystrophy • Characterized by eyelid drooping, swallowing difficulties, proximal limb weakne

  12. Slide 12: OPMD: Disease Overview

    OPMD: Disease Overview Patterns of Inheritance, Epidemiology, and Age of Onset: • Rare autosomal dominant inheritance • Prevalence of 1:100,000 (Europe) • Prevalence as high as 1:600 in specific populations • Typical age of onset is 40 years old-to-60 years old Natural History: • Progressive eyelid

  13. Slide 13: Genetic Basis of OPMD: Expansion of the Poly-Alanine Tract Within PABPN1

    Genetic Basis of OPMD: Expansion of the Poly-Alanine Tract Within PABPN1 PABPN1: • Ubiquitous factor that promotes interaction between the poly(A) polymerase and CPSF (cleavage and polyadenylation specificity factor) and, thus, controls the length of mRNA poly(A) tails, mRNA export from the nucleus,

  14. Slide 14: BB-301: Single-Vector "Silence-and-Replace" Approach

    BB-301: Single-Vector “Silence-and-Replace” Approach AAV • Non-integrating, non- BB-301 ITR Muscle Specific Codon optimized wild type PABPN1 PABPN1 PABPN1 ITR pathogenic viral delivery Promoter shRNA-1 shRNA-2 REP/CAP removed and replaced with expression cassette • To date, AAV has been used in almo

  15. Slide 15: Summary of Non-Clinical Results in The "A17" Mouse

    Summary of Non-Clinical Results in The “A17” Mouse • Multiple A17 animal cohorts received single doses of BB-301 (over a range of doses spanning 4x108 vg/muscle-to-7.5x1011 vg/muscle) and, following BB-301 administration, each cohort was observed for 14- weeks • BB-301 was injected into the Tibialis

  16. Slide 16: BB-301 Drove Dose-Dependent shRNA Expression

    BB-301 Drove Dose-Dependent shRNA Expression (Analysis Performed 14-weeks after Administration) Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 16 www.benitec.com

  17. Slide 17: BB-301 Inhibits PABPN1 Expression and Restores Near Wild Type Levels of coPABPN1

    BB-301 Inhibits PABPN1 Expression and Restores Near Wild Type Levels of coPABPN1 (Analysis Performed 14-weeks after Administration) Relative coPABPN1 Expression ((coPABPN1/GAPDH)/A17 Saline) % PABPN1 Inhibition Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 17 www.benitec.com

  18. Slide 18: BB-301 Drives Dose-Dependent Resolution of Intranuclear Inclusions in the Injected Muscles

    BB-301 Drives Dose-Dependent Resolution of Intranuclear Inclusions in the Injected Muscles Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 18 www.benitec.com

  19. Slide 19: BB-301 Restores Muscle Force to Wild Type Levels

    BB-301 Restores Muscle Force to Wild Type Levels (Analysis Performed 14-weeks after Administration) Restoration of muscle strength was assessed by muscle contractility measurements in response to a series of induced impulses that ranged from 10 to 180 Hz Copyright Copyright © Benitec Biopharma Bioph

  20. Slide 20: BB-301 Drives Robust Phenotypic Rescue over a Broad Range of Doses

    BB-301 Drives Robust Phenotypic Rescue over a Broad Range of Doses • Early signs of muscle strength restoration were observed at the 5x1010 vg/muscle dose which reduced PABPN1 expression by 31% and supported replacement of wildtype protein at 2% of normal levels • Statistically significant improveme

  21. Slide 21: IND-Enabling Non-Clinical Studies Will be Conducted Over the Next 12-to-18 Months

    IND-Enabling Non-Clinical Studies Will be Conducted Over the Next 12-to-18 Months • The IND-enabling non-clinical studies will be carried out under the guidance of the scientific team at Benitec in close collaboration with a team of Thought Leaders in both medicine and surgery that have been deeply

  22. Slide 22: BB-103 for Chronic Hepatitis B Virus Infection

    BB-103 for Chronic Hepatitis B Virus Infection • LATE-STAGE NON-CLINICAL ASSET FOR LICENSURE TO POTENTIAL PARTNERS • CATEGORY-LEADING BIOLOGICAL EFFICACY ACHIEVED IN VALIDATED ANIMAL MODEL Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 22 www.benitec.com

  23. Slide 23: BB-103 Program Overview: Biological Activity of BB-102 and BB-103 Combinations with SOC

    BB-103 Program Overview: Biological Activity of BB-102 and BB-103 Combinations with SOC on Key HBV Parameters (Seeking Strategic Partners) Log Reduction of Log Reduction Log Reduction Treatment Serum HBV DNA of HBsAg of HBeAg entecavir (ETV) 2.63 0.46 0.37 6 mg/kg daily Control groups pegylated inte

  24. Slide 24: Conclusions

    Conclusions Bolstered by robust non-clinical proof-of-concept data for BB-301, Benitec will advance BB-301 through IND-enabling studies and subsequent clinical testing in OPMD patients Continued demonstration of positive non-clinical data and early-stage clinical trial data in an orphan Muscular Dys

  25. Slide 25: Benitec Biopharma: General Financial and Capital Markets Overview

    Benitec Biopharma: General Financial and Capital Markets Overview • Market Capitalization: $6.3 million • Net Cash (March 31, 2020): $11.4 million • Public Float: 1,108,374 shares • Public Listing: – NASDAQ (Listed in 2020): BNTC Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 25

  26. Slide 26: Supplementary Slides

    SUPPLEMENTARY SLIDES Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 26 www.benitec.com

  27. Slide 27: BB-301 for Oculopharyngeal Muscular Dystrophy

    BB-301 for Oculopharyngeal Muscular Dystrophy • LATE-STAGE NON-CLINICAL ASSET WITH CATEGORY-LEADING BIOLOGICAL EFFICACY • GLOBAL PREVALENCE OF OPMD EXCEEDS 15,000 PATIENTS AND COMMERCIAL OPPORTUNITY EXCEEDS $1 BILLION Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 27 www.benitec.

  28. Slide 28: Non-Clinical Model of OPMD: The "A17" Mouse

    Non-Clinical Model of OPMD: The “A17” Mouse • Transgenic A17 mouse: expresses endogenous murine PABPN1 and a mutated bovine PABPN1 driven by the human skeletal actin promoter • Reproduces the severe muscle atrophy found in the human phenotype • Mimics other distinct pathological attributes of the hu

  29. Slide 29: Initial Development Approach: Two-Vector "Silence-and-Replace" Approach

    Initial Development Approach: Two-Vector “Silence-and-Replace” Approach • Benitec initially employed a two-vector “Silence and Replace” approach composed of: – An AAV8 vector encapsulating an expression cassette encoding three short hairpin RNA (“shRNA”) sequences whose expression would drive broad

  30. Slide 30: Initial Development Approach: Two-Vector "Silence-and-Replace" Approach

    Initial Development Approach: Two-Vector “Silence-and-Replace” Approach Intranuclear Inclusions Muscle Force, Fibrosis, CSA Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 30 www.benitec.com

  31. Slide 31: BB-301: Single-Vector "Silence-and-Replace" Approach

    BB-301: Single-Vector “Silence-and-Replace” Approach • Benitec has engineered a single-vector approach for the treatment of OPMD – This proprietary approach combines the essential elements of the initial two-vector system into a single recombinant AAV vector • The construct (BB-301) is composed of a

  32. Slide 32: BB-301 Injected at More Modest Doses Restores Muscle Force to Wild Type Levels

    BB-301 Injected at More Modest Doses Restores Muscle Force to Wild Type Levels (Analysis Performed at 14-weeks and 20-weeks after Administration) Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 32 www.benitec.com

  33. Slide 33: BB-301 Program Review

    BB-301 Program Review • Over the preceding 12-months an unsatisfactory series of BB-301-focused non-clinical experiments were conducted in large animal subjects and, due to the inherent inadequacies of the experiments, the results were inconclusive – These core non-clinical studies, therefore, requi

  34. Slide 34: Large Animal Experiments Conducted in the Past Employed Substandard Dosing Methods

    Large Animal Experiments Conducted in the Past Employed Substandard Dosing Methods and Tissue-Processing Techniques • Regarding the Prior Method of Drug Administration: An endoscopic injection procedure was employed to deliver BB-301, however, this protocol was executed without the aid of fluoroscop

  35. Slide 35: BB-103 for Chronic Hepatitis B Virus Infection

    BB-103 for Chronic Hepatitis B Virus Infection • LATE-STAGE NON-CLINICAL ASSET FOR LICENSURE TO POTENTIAL PARTNERS • CATEGORY-LEADING BIOLOGICAL EFFICACY ACHIEVED IN VALIDATED ANIMAL MODEL Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 35 www.benitec.com

  36. Slide 36: Chronic Hepatitis B Virus Infection Clinical Candidate BB-103: Product Overview

    Chronic Hepatitis B Virus Infection Clinical Candidate BB-103: Product Overview • Global prevalence estimated at 257 million people Chronic Hepatitis B Virus Infection • Need for safe and effective therapies that promote the restoration of a host immune response through targeted HBsAg knockdown • De

  37. Slide 37: shRNAs Employed in BB-301 Construct Ensure Cleavage of Multiple HBV Transcripts

    shRNAs Employed in BB-301 Construct Ensure Cleavage of Multiple HBV Transcripts HBV proteins HBeAg HBV genome HBV Transcripts shRNA 4 shRNA 8 shRNA 9 * Sequences selected for shRNA are well conserved across HBV genotypes A-H Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 37 www.b

  38. Slide 38: BB-103: Anti-HBV Agent Builds on Key Lessons from First-in-Man TT-034 Trial in HCV

    BB-103: Anti-HBV Agent Builds on Key Lessons from First-in-Man TT-034 Trial in HCV Wildtype AAV8 REP/CAP removed and replaced with expression cassette TT-034 ITR A HCV-1 B HCV-2 C HCV-3 ITR Recombinant AAV8 - HCV BB-101 BB-102 ITR A HBV-1 B HBV-2 C HBV-3 ITR Recombinant AAV8 - HBV BB-103 • Replaceme

  39. Slide 39: BB-103 vs. TT-034: Key Lessons Learned

    BB-103 vs. TT-034: Key Lessons Learned TT-034 for HCV BB-103 for HBV • Mutant promoters led to suboptimal • Wild type Pol III promoters increased expression of shRNA hairpins and modest expression of shRNA hairpins by several orders suppression of HCV replication of magnitude – Drove expression of 3

  40. Slide 40: Humanized Animal Model: PhoenixBio PXB Human Liver Chimeric Mouse

    Humanized Animal Model: PhoenixBio PXB Human Liver Chimeric Mouse 10-week old mice 3-week old mice Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 40 www.benitec.com

  41. Slide 41: In Vivo HBV Studies Using PXB Mice

    In Vivo HBV Studies Using PXB Mice 3. Transduce mice with BB-101 BB- 2. Incubate mice for 4 weeks, 102 or BB-103 at 2e13 vg/kg establish baseline HBV infection, randomize Chimeric mouse with HBV infected Chimeric mouse humanized liver 1. Infect chimeric PXB mice 4. Administer Entecavir (Daily at 6 u

  42. Slide 42: Biological Activity of BB-102 and BB-103 Combinations with SOC on Key HBV Parameters

    Biological Activity of BB-102 and BB-103 Combinations with SOC on Key HBV Parameters Log Reduction of Log Reduction Log Reduction Treatment Serum HBV DNA of HBsAg of HBeAg entecavir (ETV) 2.63 0.46 0.37 6 mg/kg daily Control groups pegylated interferon 30 mg/kg twice 2.41 0.96 1.09 weekly BB-102 1.8

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