Benitec Biopharma Inc. · NASDAQ:BNTC
Benitec Biopharma — Investor Presentation (April 2020)
42 slides from Benitec Biopharma's investor presentation, April 2020
Slide 1: Benitec Biopharma Overview
Benitec Biopharma Overview April 2020 Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 1 www.benitec.com
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,"
Slide 3: Gene Silencing: A Validated Approach to Treatment of Genetic Diseases with Some Inherent Limitations
Gene Silencing: A Validated Approach to Treatment of Genetic Diseases with Some Inherent Limitations • 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
Slide 4: Simultaneous Gene Silencing and Gene Replacement Drive Tissue-Specific Restoration of Biological Function
Simultaneous Gene Silencing and Gene Replacement Drive 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 fu
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
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
Slide 7: Benitec Biopharma: General Financial and Capital Markets Overview
Benitec Biopharma: General Financial and Capital Markets Overview • Market Capitalization: $5.3 million • Net Cash (December 31, 2019): $12.4 million • Public Float: 1,070,957 shares • Public Listing: – NASDAQ (Listed in 2020): BNTC Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec
Slide 8: Corporate and Scientific Team
Corporate and Scientific Team • Deep expertise in gene therapy • Internal manufacturing expertise – Demonstrated capabilities for optimization of complex, scalable, AAV-based manufacturing processes • Management team with background in operations and capital allocation within the biopharmaceutical s
Slide 9: 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
Slide 10: 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
Slide 11: 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
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 $1 BILLION Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 12 www.benitec.
Slide 13: 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
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: 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
Slide 17: 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
Slide 18: 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 18 www.benitec.com
Slide 19: 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
Slide 20: 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
Slide 21: 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
Slide 22: 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 22 www.benitec.com
Slide 23: 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 Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 23 www.benitec.
Slide 24: 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 24 www.benitec.com
Slide 25: 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
Slide 26: BB-301 Drives Robust Phenotype Rescue over a Broad Range of Doses
BB-301 Drives Robust Phenotype 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 improvemen
Slide 27: 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 27 www.benitec.com
Slide 28: 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
Slide 29: Large Animal Experiments Conducted in the Past Employed Substandard Dosing Methods and Tissue-Processing Techniques
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
Slide 30: 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 31: 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 31 www.benitec.com
Slide 32: BB-103 Program Overview: Biological Activity of BB-102 and BB-103 Combinations with SOC on Key HBV Parameters
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 33: 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 34: SUPPLEMENTARY SLIDES
SUPPLEMENTARY SLIDES Copyright Copyright © Benitec Biopharma BiopharmaLtd Inc © Benitec 34 www.benitec.com
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
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
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
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
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
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
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
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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