Benitec Biopharma Inc. · NASDAQ:BNTC

Benitec Biopharma — Investor Presentation (September 2019)

40 slides from Benitec Biopharma's investor presentation, September 2019

  1. Slide 1: Benitec Corporate Overview

    Benitec Corporate Overview September 2019 Copyright © Benitec Biopharma Ltd 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: Benitec Biopharma: General Financial and Capital Markets Overview

    Benitec Biopharma: General Financial and Capital Markets Overview • Benitec Biopharma: Gene therapy-focused biotechnology company developing novel genetic medicines derived from the proprietary DNA-directed RNA interference (“ddRNAi”) platform • Market Cap: USD$8.6 million • Net Cash (June 30, 2019)

  4. Slide 4: 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

  5. Slide 5: 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. • The use of shRNA/miRNA hybrids confers Drosha advantages with respect to expression, safety, miRNA gene Pri-miRNA Pre-miRNA Transcription and specificity Pol II Nucleus Exportin 5 • Perfec

  6. Slide 6: Corporate and Scientific Team

    Corporate and Scientific Team • Deep expertise in gene therapy • Scientific operations in Hayward, California • Internal manufacturing expertise – Demonstrated capabilities for optimization of complex, scalable, AAV-based manufacturing processes • Management team with background in operations and ca

  7. Slide 7: Executive Team

    Executive Team • Jerel Banks, M.D., Ph.D. • Claudia Kloth, Ph.D. – CEO and Executive Chairman – SVP of Manufacturing – Healthcare investment professional with over 13 – Over 20 years of cGMP manufacturing and years of experience process development experience in therapeutics – Former vice president

  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 IND- Early stage clinical Late stage clinical Commercial Program Delivery Discovery Preclinical Enabling (IND – Phase 2) (Phase 2 – Phase 3) Rights Proprietary Pipeline Assets with Peer-Reviewed Proof-of-Conc

  9. Slide 9: Broad Intellectual Property Portfolio for Lead Research Programs

    Broad Intellectual Property Portfolio for Lead Research Programs • 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

  10. Slide 10: BB-301 Program Overview

    BB-301 Program Overview • BB-301 is an internally optimized, AAV-based gene therapy agent that can both silence the expression of the mutated, disease-causing PABPN1 gene (to slow, or halt, the underlying mechanism of disease progression in OPMD) and replace the mutant PABPN1 gene with a normal, “wi

  11. Slide 11: BB-301 Program Overview

    BB-301 Program Overview • Over the preceding 12-months, an incomplete set of BB-301-focused non-clinical experiments were conducted in large animal subjects, the results of which were inconclusive • As these non-clinical studies require repetition, Benitec will complete three non-clinical studies fo

  12. Slide 12: 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 Investors) 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 int

  13. Slide 13: 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 USD$1 BILLION Copyright © Benitec Biopharma Ltd 13 www.benitec.com

  14. Slide 14: Oculopharyngeal Muscular Dystrophy Clinical Candidate BB-301: Product Overview

    Oculopharyngeal Muscular Dystrophy Clinical 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 we

  15. Slide 15: 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 in 40’s-to-60’s Natural History: • Progressive eyelid drooping (pto

  16. Slide 16: 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, a

  17. Slide 17: 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 a prior two-vector system (described in the supplementary slides) into a single recombinant AAV vector • The c

  18. Slide 18: 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 almost

  19. Slide 19: Non-Clinical Model of OPMD: The 'A17' Mouse

    Non-Clinical Model of OPMD: The ‘A17’ Mouse • Transgenic A17 mouse: expresses a mutated bovine PABPN1 driven by the human skeletal actin promoter in addition to the endogenous PABPN1 • Reproduces the severe muscle atrophy found in the human phenotype • Mimics other distinct pathological attributes o

  20. Slide 20: Summary of Non-Clinical Results in The 'A17' Mouse

    Summary of Non-Clinical Results in The ‘A17’ Mouse • The experiment was performed over 14-weeks to evaluate the activity of BB-301 as single doses administered at 4x108 to 7.5x1011 vg/muscle • A single dose of vector was injected into the Tibialis Anterior (TA) muscle of 10-12 week old A17 mice at c

  21. Slide 21: BB-301 Drove Dose-Dependent shRNA Expression

    BB-301 Drove Dose-Dependent shRNA Expression (Analysis Performed 14-weeks after Administration) Copyright © Benitec Biopharma Ltd 21 www.benitec.com

  22. Slide 22: BB-301 Inhibits Mutant PABPN1 Expression and Restores Near Wild Type Levels of coPABPN1

    BB-301 Inhibits Mutant 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 © Benitec Biopharma Ltd 22 www.benitec.com

  23. Slide 23: 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 © Benitec Biopharma Ltd 23 www.benitec.com

  24. Slide 24: 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 © Benitec Biopharma Ltd 24 www.beni

  25. Slide 25: BB-301 Drives Robust Phenotype Rescue over a Broad Range of Doses

    BB-301 Drives Robust Phenotype Rescue over a Broad Range of Doses • Data suggest that modest restoration of strength (at the 5x1010 vg/muscle dose) occurs at 31% PABPN1 inhibition when coupled with wildtype protein expression at 2% of normal levels • 2.5x1011 vg/muscle resulted in complete maximal f

  26. Slide 26: BB-301 Injected at "Suboptimal" Doses Restores Muscle Force to Wild Type Levels

    BB-301 Injected at “Suboptimal” Doses Restores Muscle Force to Wild Type Levels (Analysis Performed at 14-weeks and 20-weeks after Administration) Copyright © Benitec Biopharma Ltd 26 www.benitec.com

  27. Slide 27: Non-Clinical Experiments in Canines Employed Inconsistent Dosing Methods and Tissue-Processing Techniques

    Non-Clinical Experiments Conducted During the Past 12-months in Canines Employed Inconsistent Dosing Methods and Tissue-Processing Techniques • An endoscopic procedure was employed, without the aid of fluoroscopy or electromyography, to directly inject BB-301 into the muscles of interest in canines

  28. Slide 28: New BB-301 Non-Clinical Studies Will be Conducted Over the Next 12-to-18 Months

    New BB-301 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 en

  29. Slide 29: 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

  30. Slide 30: Supplementary Slides

    September 2019 SUPPLEMENTARY SLIDES Copyright © Benitec Biopharma Ltd 30 www.benitec.com

  31. Slide 31: 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 USD$1 BILLION Copyright © Benitec Biopharma Ltd 31 www.benitec.com

  32. Slide 32: Two-Vector "Silence-and-Replace" Approach for the Treatment of OPMD

    Two-Vector “Silence-and-Replace” Approach for the Treatment of OPMD • Benitec previously designed a two-vector gene therapy strategy that significantly ameliorated the OPMD-derived pathology in the A17 mouse model of the disease (the A17 mouse model is described on Slide 20) • This initial approach

  33. Slide 33: 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 © Benitec Biopharma Ltd 33 www.benitec.com

  34. Slide 34: 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

  35. Slide 35: 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 © Benitec Biopharma Ltd 35 www.benitec.com

  36. Slide 36: 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

  37. Slide 37: 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

  38. Slide 38: 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 © Benitec Biopharma Ltd 38 www.benitec.com

  39. Slide 39: 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

  40. Slide 40: 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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