Benitec Biopharma Inc. · NASDAQ:BNTC

Benitec Biopharma — Ladenburg Thalmann Healthcare Conference 2019

39 slides from Benitec Biopharma's conference presentation, September 2019

Slide 2: 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)
Slide 3: Platform Enables Gene Therapy and Permanent Gene Silencing: 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
Slide 4: Mechanism of RNA Interference Through the microRNA (miRNA) Pathway
Mechanism of RNA Interference Through the microRNA (miRNA) Pathway • The use of shRNA/miRNA hybrids confers advantages with respect to expression, safety, and specificity • Perfect complementary hairpins are processed by cellular RNAse-III like enzymes at different positions, and a single “perfect”
Slide 5: 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
Slide 6: 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
Slide 7: Pipeline: 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
Slide 8: 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
Slide 9: 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
Slide 10: 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
Slide 11: 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
Slide 12: 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 12 www.benitec.com
Slide 13: OPMD 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
Slide 14: 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
Slide 15: 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
Slide 16: 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
Slide 17: 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
Slide 18: 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
Slide 19: 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
Slide 20: BB-301 Drove Dose-Dependent shRNA Expression
BB-301 Drove Dose-Dependent shRNA Expression (Analysis Performed 14-weeks after Administration) Copyright © Benitec Biopharma Ltd 20 www.benitec.com
Slide 21: 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 21 www.benitec.com
Slide 22: BB-301 Drives Dose-Dependent Resolution of Intranuclear Inclusions
BB-301 Drives Dose-Dependent Resolution of Intranuclear Inclusions in the Injected Muscles Copyright © Benitec Biopharma Ltd 22 www.benitec.com
Slide 23: 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 23 www.beni
Slide 24: 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
Slide 25: 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 25 www.benitec.com
Slide 26: Non-Clinical Canine Experiments 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
Slide 27: 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
Slide 28: 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
Slide 30: 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 30 www.benitec.com
Slide 31: 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
Slide 32: 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 32 www.benitec.com
Slide 33: 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
Slide 34: 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 34 www.benitec.com
Slide 35: 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
Slide 36: 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
Slide 37: 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 37 www.benitec.com
Slide 38: 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
Slide 39: 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

Benitec Biopharma — Ladenburg Thalmann Healthcare Conference 2019 on 6ix

Benitec Biopharma — Ladenburg Thalmann Healthcare Conference 2019

Slide 1: Benitec Corporate Overview

Slide 2: Benitec Biopharma: General Financial and Capital Markets Overview

Slide 3: Platform Enables Gene Therapy and Permanent Gene Silencing: ddRNAi

Slide 4: Mechanism of RNA Interference Through the microRNA (miRNA) Pathway

Slide 5: Corporate and Scientific Team

Slide 6: Executive Team

Slide 7: Pipeline: OPMD and Chronic Hepatitis B Virus Infection

Slide 8: Broad Intellectual Property Portfolio for Lead Research Programs

Slide 9: BB-301 Program Overview

Slide 10: BB-301 Program Overview

Slide 11: BB-103 Program Overview: Biological Activity of BB-102 and BB-103 Combinations with SOC

Slide 12: BB-301 for Oculopharyngeal Muscular Dystrophy

Slide 13: OPMD Clinical Candidate BB-301: Product Overview

Slide 14: OPMD: Disease Overview

Slide 15: Genetic Basis of OPMD: Expansion of the Poly-Alanine Tract Within PABPN1

Slide 16: BB-301: Single-Vector Silence-and-Replace Approach

Slide 17: BB-301: Single-Vector Silence-and-Replace Approach

Slide 18: Non-Clinical Model of OPMD: The 'A17' Mouse

Slide 19: Summary of Non-Clinical Results in The 'A17' Mouse

Slide 20: BB-301 Drove Dose-Dependent shRNA Expression

Slide 21: BB-301 Inhibits Mutant PABPN1 Expression and Restores Near Wild Type Levels of coPABPN1

Slide 22: BB-301 Drives Dose-Dependent Resolution of Intranuclear Inclusions

Slide 23: BB-301 Restores Muscle Force to Wild Type Levels

Slide 24: BB-301 Drives Robust Phenotype Rescue over a Broad Range of Doses

Slide 25: BB-301 Injected at Suboptimal Doses Restores Muscle Force to Wild Type Levels

Slide 26: Non-Clinical Canine Experiments Employed Inconsistent Dosing Methods and Tissue-Processing Techniques

Slide 27: New BB-301 Non-Clinical Studies Will be Conducted Over the Next 12-to-18 Months

Slide 28: Conclusions

Slide 29: Supplementary Slides

Slide 30: BB-301 for Oculopharyngeal Muscular Dystrophy

Slide 31: Two-Vector Silence-and-Replace Approach for the Treatment of OPMD

Slide 32: BB-103 for Chronic Hepatitis B Virus Infection

Slide 33: Chronic Hepatitis B Virus Infection Clinical Candidate BB-103: Product Overview

Slide 34: shRNAs Employed in BB-301 Construct Ensure Cleavage of Multiple HBV Transcripts

Slide 35: BB-103: Anti-HBV Agent Builds on Key Lessons from First-in-Man TT-034 Trial in HCV

Slide 36: BB-103 vs. TT-034: Key Lessons Learned

Slide 37: Humanized Animal Model: PhoenixBio PXB Human Liver Chimeric Mouse

Slide 38: In Vivo HBV Studies Using PXB Mice

Slide 39: Biological Activity of BB-102 and BB-103 Combinations with SOC on Key HBV Parameters