Benitec Biopharma Inc. · NASDAQ:BNTC

Benitec Biopharma — Investor Presentation (September 2021)

39 slides from Benitec Biopharma's investor presentation, September 2021

1. Slide 1: Benitec Biopharma Overview

   Benitec Biopharma Overview September 2021 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 DNA-directed RNA interference (ddRNAi) platform combines RNAi with classical AAV-based gene therapy • Via the ddRNAi platform Benitec creates genetic medicines that, following a s

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: 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 over 15 – Over 20 years of cGMP manufacturing and ye

7. Slide 7: 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 7 www.benitec.com

8. Slide 8: 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

9. Slide 9: 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 OVER THE LIFE OF THE PRODUCT Copyright Copyright © Benitec Biopharma BiopharmaLtd

10. Slide 10: 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

11. Slide 11: 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

12. Slide 12: 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,

13. Slide 13: 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

14. Slide 14: 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

15. Slide 15: 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 15 www.benitec.com

16. Slide 16: 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 16 www.benitec.com

17. Slide 17: 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 17 www.benitec.com

18. Slide 18: 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

19. Slide 19: 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

20. Slide 20: CTA-Enabling and IND-Enabling Studies for BB-301 to be Completed Over the Next Twelve Months

    CTA-Enabling and IND-Enabling Studies for BB-301 to be Completed Over the Next Twelve Months • Benitec previously disclosed key data-points related to the non-clinical studies for BB-301 that were anticipated to support the filing of Clinical Trial Applications (CTA) in Europe and in Canada and, sim

21. Slide 21: 8-Week BB-301 Pilot Dosing Study in Beagle Dogs: Study Rationale and Background

    8-Week BB-301 Pilot Dosing Study in Beagle Dogs: Study Rationale and Background • BB-301 is directly injected into the pharyngeal muscles known to underlie the morbidity and mortality characterizing the natural history of OPMD, and large animals (e.g. canine subjects) possess anatomical architecture

22. Slide 22: 8-Week BB-301 Pilot Dosing Study in Beagle Dogs: Study Design and Background

    8-Week BB-301 Pilot Dosing Study in Beagle Dogs: Study Design and Background • The 8-week Pilot Dosing Study evaluated the safety and biological activity of two concentrations of BB-301 (1.0+E13 vg/mL and 3.0+E13 vg/mL) across three distinct doses (1.0+E13 vg/mL, 3.0+E13 vg/mL with a low injection v

23. Slide 23: Interim Results for the Pilot Dosing Study: Summary of the Key Observations to Date

    Interim Results for the Pilot Dosing Study: Summary of the Key Observations to Date An interim analysis of the BB-301 Pilot Dosing Study in Beagle dogs revealed: • Biologically significant, dose-dependent levels of BB-301 tissue transduction (i.e. delivery of the multi- functional genetic construct

24. Slide 24: Interim Results for the Pilot Dosing Study: Pharyngeal Muscle Tissue Transduction Levels for BB-301

    Interim Results for the Pilot Dosing Study: Pharyngeal Muscle Tissue Transduction Levels for BB-301 • The data demonstrate the achievement of biologically significant, dose-dependent levels of BB-301 tissue transduction (i.e. delivery of the multi-functional genetic construct into the target pharyng

25. Slide 25: Interim Results for the Pilot Dosing Study: Gene Expression Levels for BB-301 within Pharyngeal Muscles

    Interim Results for the Pilot Dosing Study: Gene Expression Levels for BB-301 within Pharyngeal Muscles • BB-301 encodes 2 distinct siRNA species (i.e. siRNA13 and siRNA17) which are each, independently, capable of inhibiting (i.e. “silencing”) the expression of the mutant form of the PABPN1 protein

26. Slide 26: Interim Results for the Pilot Dosing Study: Gene Expression Levels for BB-301 within Pharyngeal Muscles

    Interim Results for the Pilot Dosing Study: Gene Expression Levels for BB-301 within Pharyngeal Muscles • The data demonstrate the achievement of broad-based, dose-dependent expression of siRNA13 within the pharyngeal muscle cells Avg. Reported siRNA13 copies per cell 600,000 500,000 400,000 300,000

27. Slide 27: Interim Results for the Pilot Dosing Study: Gene Expression Levels for BB-301 within Pharyngeal Muscles

    Interim Results for the Pilot Dosing Study: Gene Expression Levels for BB-301 within Pharyngeal Muscles • The data demonstrate the achievement of broad-based, dose-dependent expression of siRNA17 within the pharyngeal muscle cells Avg. Reported siRNA17 copies per cell 120,000 100,000 80,000 60,000 4

28. Slide 28: Interim Results for the Pilot Dosing Study: Gene Expression Levels for BB-301 within Pharyngeal Muscles

    Interim Results for the Pilot Dosing Study: Gene Expression Levels for BB-301 within Pharyngeal Muscles • The data demonstrate the achievement of broad-based, dose-dependent expression of codon optimized PABPN1 within the pharyngeal muscle cells Avg. Reported coPABPN1 copies per cell 90.00 80.00 70.

29. Slide 29: Interim Results for the Pilot Dosing Study: PABPN1 Silencing within Pharyngeal Muscles

    Interim Results for the Pilot Dosing Study: PABPN1 Silencing (i.e. target “knock-down”) within Pharyngeal Muscles • As noted above, BB-301 encodes 2 distinct siRNA species (i.e. siRNA13 and siRNA17) which are each, independently, capable of inhibiting (i.e. “silencing”) the expression of all forms o

30. Slide 30: Interim Results for the Pilot Dosing Study: PABPN1 Silencing within Pharyngeal Muscles

    Interim Results for the Pilot Dosing Study: PABPN1 Silencing (i.e. target “knock-down”) within Pharyngeal Muscles • An interim analysis of the level of PABPN1 silencing achieved at 8-weeks revealed durable and biologically significant levels of target gene knock-down (i.e. inhibition of the expressi

31. Slide 31: Pilot Dosing Study: Key Methodological Improvements to the Study Design and Analytical Procedures

    BB-301 Pilot Dosing Study: Key Methodological Improvements to the Study Design and Analytical Procedures • It is critical to highlight the key methodological distinctions between the current BB-301 Pilot Dosing Study in Beagle dogs conducted by Benitec as compared to the prior BB-301 Beagle dog dosi

32. Slide 32: Pilot Dosing Study: Key Methodological Improvements to the Study Design and Analytical Procedures

    BB-301 Pilot Dosing Study: Key Methodological Improvements to the Study Design and Analytical Procedures • These newly developed proprietary methods of BB-301 delivery, as well as the analytical methods developed to evaluate the key target tissues of the Beagle dog subjects, led to broad-based trans

33. Slide 33: Pilot Dosing Study: Key Methodological Improvements to the Study Design and Analytical Procedures

    BB-301 Pilot Dosing Study: Key Methodological Improvements to the Study Design and Analytical Procedures • These newly developed proprietary methods of BB-301 delivery, as well as the analytical methods developed to evaluate the key target tissues of the Beagle dog subjects, demonstrated a 228-fold

34. Slide 34: Development Program: Key Regulatory Updates

    BB-301 Development Program: Key Regulatory Updates • Benitec completed a Scientific Advice Meeting in France in the first half of 2021 • The Scientific Advice Meeting was conducted to review and confirm the adequacy of: – The non-clinical data derived from the evaluation of BB-301 in both the murine

35. Slide 35: Development Program: Key Regulatory Updates

    BB-301 Development Program: Key Regulatory Updates • Regarding European Regulatory Interactions: – The BB-301 Pilot Dosing Study was viewed as an appropriate dose range finding study – The design of the ongoing GLP Biodistribution and Toxicology study was viewed as appropriate to support Phase 1b/2a

36. Slide 36: Development Program: Key Regulatory Updates

    BB-301 Development Program: Key Regulatory Updates • Regarding U.S. Regulatory Interactions: – Benitec has been granted a Type C meeting with the U.S. Food and Drug Administration (“FDA”) in the fourth quarter of 2021 Copyright © Benitec Biopharma Ltd 36 www.benitec.com

37. Slide 37: Development Program: Key Development Updates

    BB-301 Development Program: Key Development Updates • BB-301 Phase 1b/2a Clinical Study Design for 2022 – Study Rationale: • Evaluate the safety, tolerability, and clinical activity of ascending doses of BB-301 administered to subjects with OPMD via local intramuscular (IM) injection into the middle

38. Slide 38: Development Program: Key Development Updates

    BB-301 Development Program: Key Development Updates • Primary Endpoint (assessed at screening and through end of treatment): • To assess the safety and tolerability of ascending IM doses of BB-301 • Secondary Endpoints (assessed at Day -180, Day -90, Day -2, Day 90, Day 180, Day 270, Day 360): • To

39. Slide 39: Benitec Pipeline Updates: Key Upcoming Milestones

    Benitec Pipeline Updates: Key Upcoming Milestones • Initiation of the Phase 1b/2a clinical study of BB-301 in OPMD patients in 2022 • Benitec plans to provide additional pipeline updates in the second half of 2021 Copyright © Benitec Biopharma Ltd 39 www.benitec.com

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