Benitec Biopharma Inc. · NASDAQ:BNTC
Benitec Biopharma — Technical Presentation (February 2021)
27 slides from Benitec Biopharma's technical presentation, February 2021
Slide 1: Interim Results of IND-Enabling Large Animal Study for BB-301
Interim Results of IND-Enabling Large Animal Study for BB-301 February 2021 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 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
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 • Through the use of the ddRNAi platform Benitec creates genetic medicines that
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: 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
Slide 7: 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 8: 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,
Slide 9: 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 10: IND-Enabling Studies for BB-301 to Be Completed Over the Next 12-to-18 Months
IND-Enabling Studies for BB-301 to be Completed Over the Next 12-to-18 Months • The IND-enabling non-clinical studies outlined below are being 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
Slide 11: 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
Slide 12: 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
Slide 13: 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, highly-consistent, dose-dependent levels of BB-301 tissue transduction (i.e. delivery of the multi-functional
Slide 14: Pharyngeal Muscle Tissue Transduction Levels for BB-301
Interim Results for the Pilot Dosing Study: Pharyngeal Muscle Tissue Transduction Levels for BB-301 • An interim analysis of the BB-301 pharyngeal muscle tissue transduction levels revealed biologically significant, highly-consistent, dose-dependent levels of BB-301 tissue transduction (i.e. deliver
Slide 15: Pharyngeal Muscle Tissue Transduction Levels for BB-301
Interim Results for the Pilot Dosing Study: Pharyngeal Muscle Tissue Transduction Levels for BB-301 Avg. Reported BB-301 copies per cell 10.0 9.0 8.6 8.0 7.0 7.2 6.0 5.0 4.0 3.0 3.5 2.0 2.3 2.0 1.7 1.0 0.0 1+E13 vg/mL 3+E13 vg/mL Low Volume 3+E13 vg/mL High Volume 1+E13 vg/mL 3+E13 vg/mL Low Volume
Slide 16: 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 two distinct siRNA species: – siRNA13 – siRNA17 • BB-301 encodes 2 distinct siRNA species (i.e. siRNA13 and siRNA17) which are each, independently, capable of inhibiting (i.e. “si
Slide 17: 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 • An interim analysis of the BB-301 expression levels within the target pharyngeal muscle tissues revealed biologically significant, highly-consistent, dose-dependent levels of gene expression • I
Slide 18: siRNA13 Expression Levels for BB-301 within Pharyngeal Muscles
Interim Results for the Pilot Dosing Study: siRNA13 Expression Levels for BB-301 within Pharyngeal Muscles Avg. Reported siRNA13 copies per cell 800,000 700,000 600,000 500,000 400,000 300,000 200,000 100,000 0 1+E13 vg/mL 3+E13 vg/mL Low Volume 3+E13 vg/mL High Volume 1+E13 vg/mL 3+E13 vg/mL Low Vo
Slide 19: siRNA17 Expression Levels for BB-301 within Pharyngeal Muscles
Interim Results for the Pilot Dosing Study: siRNA17 Expression Levels for BB-301 within Pharyngeal Muscles Avg. Reported siRNA17 copies per cell 200,000 180,000 160,000 140,000 120,000 100,000 80,000 60,000 40,000 20,000 0 1+E13 vg/mL 3+E13 vg/mL Low Volume 3+E13 vg/mL High Volume 1+E13 vg/mL 3+E13
Slide 20: coPABPN1 Expression Levels for BB-301 within Pharyngeal Muscles
Interim Results for the Pilot Dosing Study: coPABPN1 Expression Levels for BB-301 within Pharyngeal Muscles Avg. Reported coPABPN1 copies per cell 120.00 100.00 80.00 60.00 40.00 20.00 0.00 1+E13 vg/mL 3+E13 vg/mL Low Volume 3+E13 vg/mL High Volume 1+E13 vg/mL 3+E13 vg/mL Low Volume 3+E13 vg/mL High
Slide 21: PABPN1 Silencing (i.e. target “knock-down”) 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
Slide 22: PABPN1 Silencing (i.e. target “knock-down”) 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
Slide 23: PABPN1 Silencing (i.e. target “knock-down”) within Pharyngeal Muscles
Interim Results for the Pilot Dosing Study: PABPN1 Silencing (i.e. target “knock-down”) within Pharyngeal Muscles Avg. Reported % Inhibition of wtPABPN1 90 80 70 60 50 40 30 20 10 0 1+E13 vg/mL 3+E13 vg/mL Low Volume 3+E13 vg/mL High Volume 1+E13 vg/mL 3+E13 vg/mL Low Volume 3+E13 vg/mL High Volume
Slide 24: BB-301 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 and the prior Beagle dog dosing study carried o
Slide 25: BB-301 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 Avg. Reported BB-301 copies per cell within Target Tissues Following 1+E13 Dosing 2.50 2.00 1.50 1.00 0.50 0.00 Benitec Inc. (HP Muscle) Former BB-301 Licensee (HP Muscle) Benitec Inc. (TP Muscle
Slide 26: Interim Results for the Pilot Dosing Study: Summary of the Key Conclusions
Interim Results for the Pilot Dosing Study: Summary of the Key Conclusions An interim analysis of the BB-301 Pilot Dosing Study in Beagle dogs revealed: • Biologically significant, highly-consistent, dose-dependent levels of BB-301 tissue transduction – BB-301 copy numbers ranging from 1.7 copies pe
Slide 27: BB-301 Development Program and Benitec Pipeline Updates: Key Upcoming Milestones
BB-301 Development Program and Benitec Pipeline Updates: Key Upcoming Milestones • Benitec has scheduled a Scientific Advice Meeting in France in May 2021 to review the interim data and the Phase 1 clinical trial design • Benitec continues to plan for the initiation of the first-in-human clinical st
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