Benitec Biopharma Inc. · NASDAQ:BNTC
Benitec Biopharma — Ladenburg Thalmann Healthcare Conference 2019
39 slides from Benitec Biopharma's conference presentation, Sep 24, 2019
Slide 1: Benitec Corporate Overview
Benitec Corporate Overview Ladenburg Thalmann September 2019 Exhibit 99.1
Slide 2: 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$8.6 million Net Cash (June 30, 2019): USD$
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 with gene therapy delivery Long-term therapeutic potential from a single administration Constant, steady-state levels of shRNA expression Silence a single gene or target multi
Slide 4: Mechanism of RNA Interference Through the 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” shRN
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 capital allo
Slide 6: Executive Team
Executive Team Jerel Banks, M.D., Ph.D. CEO and Executive Chairman Healthcare investment professional with over 13 years of experience Former vice president and co-portfolio manager at Franklin Templeton Investments Earned an M.D. and Ph.D. at Brown University, and holds an A.B. in Chemistry from Pr
Slide 7: Pipeline: OPMD and Chronic Hepatitis B Virus Infection
Pipeline: Oculopharyngeal Muscular Dystrophy (OPMD) and Chronic Hepatitis B Virus Infection Program Delivery Discovery Preclinical IND-Enabling Early stage clinical (IND – Phase 2) Late stage clinical (Phase 2 – Phase 3) Commercial Rights Proprietary Pipeline Assets with Peer-Reviewed Proof-of-Conce
Slide 8: Broad Intellectual Property Portfolio for Lead Research Programs
Broad Intellectual Property Portfolio for Lead Research Programs OPMD-related intellectual property: OPMD Family 4 anticipated expiry February 2040 OPMD Family 3 anticipated expiry October 2039 OPMD Family 2 anticipated expiry December 2037 OPMD Family 1 anticipated expiry April 2037 AAV-related int
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, “wild
Slide 10: BB-301 Program Overview: Non-clinical Studies and IND Path
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 for BB
Slide 11: BB-103 Program Overview: Biological Activity of BB-102 and BB-103 with SOC
BB-103 Program Overview: Biological Activity of BB-102 and BB-103 Combinations with SOC on Key HBV Parameters (Seeking Strategic Investors) Treatment Log Reduction of Serum HBV DNA Log Reduction of HBsAg Log Reduction of HBeAg Control groups entecavir (ETV) 6 mg/kg daily 2.63 0.46 0.37 pegylated int
Slide 12: Late-Stage Non-clinical Asset: BB-301 for OPMD
Late-Stage Non-clinical Asset with Category-leading biological efficacy BB-301 for Oculopharyngeal Muscular Dystrophy Global prevalence of OPMD exceeds 15,000 patients and commercial opportunity exceeds USD$1 billion
Slide 13: BB-301: Product Overview
Oculopharyngeal Muscular Dystrophy Clinical Candidate BB-301: Product Overview Oculopharyngeal Muscular Dystrophy BB-301 Product Profile/Milestones Designed to treat dysphagia associated with OPMD Value / Commercial Opportunity US and EU Orphan status provides expeditious commercialization path ‘Sil
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 (ptosis) Progr
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, and
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 constru
Slide 17: BB-301: Single-Vector Silence-and-Replace Approach
REP/CAP removed and replaced with expression cassette AAV Non-integrating, non-pathogenic viral delivery To date, AAV has been used in almost 200 clinical trials Sustained expression (years) following single injection BB-301: Single-Vector Silence-and-Replace Approach “Silence” “Replace” BB-301 ITR
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 of the
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 conce
Slide 20: BB-301 Drove Dose-Dependent shRNA Expression
BB-301 Drove Dose-Dependent shRNA Expression (Analysis Performed 14-weeks after Administration)
Slide 21: BB-301 Inhibits Mutant PABPN1 and Restores Near Wild Type coPABPN1
BB-301 Inhibits Mutant PABPN1 Expression and Restores Near Wild Type Levels of coPABPN1 (Analysis Performed 14-weeks after Administration) % PABPN1 Inhibition Relative coPABPN1 Expression ((coPABPN1/GAPDH)/A17 Saline)
Slide 22: BB-301 Drives Dose-Dependent Resolution of Intranuclear Inclusions
BB-301 Drives Dose-Dependent Resolution of Intranuclear Inclusions in the Injected Muscles
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
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 force
Slide 25: BB-301 at Suboptimal Doses Restores Muscle Force
BB-301 Injected at “Suboptimal” Doses Restores Muscle Force to Wild Type Levels (Analysis Performed at 14-weeks and 20-weeks after Administration)
Slide 26: Canine Experiments Employed Inconsistent Dosing and Tissue-Processing Methods
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 Th
Slide 27: New BB-301 Non-Clinical Studies 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 enga
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 29: Supplementary Slides
Supplementary Slides September 2019
Slide 30: Late-Stage Non-clinical Asset: BB-301 for OPMD
Late-Stage Non-clinical Asset with Category-leading biological efficacy BB-301 for Oculopharyngeal Muscular Dystrophy Global prevalence of OPMD exceeds 15,000 patients and commercial opportunity exceeds USD$1 billion
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 was
Slide 32: Late-Stage Non-clinical Asset for Licensure: BB-103 for Hepatitis B
Late-Stage Non-clinical Asset for Licensure to Potential Partners BB-103 for Chronic Hepatitis B Virus Infection Category-Leading Biological Efficacy Achieved in Validated animal model
Slide 33: BB-103: Product Overview
Chronic Hepatitis B Virus Infection Clinical Candidate BB-103: Product Overview Chronic Hepatitis B Virus Infection BB-103 Product Profile/Milestones Designed as a single-dose treatment to be paired with existing standard of care Value / Commercial Opportunity BB-103 is the only gene silencing agent
Slide 34: shRNAs Ensure Cleavage of Multiple HBV Transcripts
shRNAs Employed in BB-301 Construct Ensure Cleavage of Multiple HBV Transcripts shRNA 9 shRNA 4 HBV proteins HBV Transcripts HBV genome shRNA 8 * Sequences selected for shRNA are well conserved across HBV genotypes A-H HBeAg
Slide 35: BB-103: Anti-HBV Agent Builds on Lessons from TT-034 Trial
Replacement of three anti-HBV shRNA into anti-HCV shRNA positions Maintains AAV8 capsid – biodistribution identical to TT-034 (can use other capsids) Employs optimal aspects of the recombinant expression cassette TT-034 clinical data guides HBV Protocol development and provides simpler regulatory pa
Slide 36: BB-103 vs. TT-034: Key Lessons Learned
BB-103 vs. TT-034: Key Lessons Learned TT-034 for HCV Mutant promoters led to suboptimal expression of shRNA hairpins and modest suppression of HCV replication Drove expression of 3-to-191 shRNA copies per cell Wild type shRNA constructs drove variable expression of biologically active hairpins Led
Slide 37: Humanized Animal Model: PhoenixBio PXB Human Liver Chimeric Mouse
Humanized Animal Model: PhoenixBio PXB Human Liver Chimeric Mouse 3-week old mice 10-week old mice
Slide 38: In Vivo HBV Studies Using PXB Mice
In Vivo HBV Studies Using PXB Mice Chimeric mouse with humanized liver 1. Infect chimeric PXB mice with HBV genotype C 2. Transduce mice with BB-101 BB-102 or BB-103 at 2e13 vg/kg Administer Entecavir (Daily at 6 ug/kg) or Pegylated Interferon (twice weekly at 30 ug/kg) Serum (weekly): Extracellular
Slide 39: Biological Activity of BB-102 and BB-103 Combinations with SOC
Biological Activity of BB-102 and BB-103 Combinations with SOC on Key HBV Parameters Treatment Log Reduction of Serum HBV DNA Log Reduction of HBsAg Log Reduction of HBeAg Control groups entecavir (ETV) 6 mg/kg daily 2.63 0.46 0.37 pegylated interferon 30 mg/kg twice weekly 2.41 0.96 1.09 Single adm
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