Benitec Biopharma Inc. · NASDAQ:BNTC
Benitec Biopharma — Cell & Gene Meeting on the Mesa (October 2017)
23 slides from Benitec Biopharma's conference presentation, Oct 5, 2017
Slide 1: Cell & Gene Meeting on the Mesa
NASDAQ: BNTC ASX: BLT Cell & Gene Meeting on the Mesa David Suhy Chief Scientific Officer
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: Business Overview
Business Overview A multi-product clinical stage company in 2018 Benitec has created a novel combination of gene therapy and RNA interference (gene silencing) to change treatment paradigms of human disease PROVEN TECHNOLOGY Validated technology with two clinical assets by the end of 2018 ROBUST PIPE
Slide 4: Experienced Executive Team
Experienced Executive Team Greg West • Former CFO of Benitec Biopharma, 10 years biotech experience Chief Executive Officer • Prior roles at PriceWaterhouse, Bankers Trust, Deutsche Bank and NZI Dr. David Suhy • Former SVP of Research & Development, Benitec Biopharma Chief Scientific Officer • Prior
Slide 5: Company Highlights
Company Highlights Programs advancing to the clinic • Phase II ready EGFR-targeted gene silencing therapeutic achieved POC in head & neck cancer entering confirmatory Phase II trial in Q1 2018. • Unique “silence and replace” therapeutic against orphan disease oculopharyngeal muscular dystrophy by si
Slide 6: Permanent Gene Silencing with DNA-Directed RNA Interference (ddRNAi)
Permanent Gene Silencing with DNA-Directed RNA Interference (ddRNAi) • Combines RNA interference with gene therapy Transient gene silencing - siRNA Permanent gene silencing - ddRNAi delivery • Long term therapeutic potential from a single administration • Constant, steady state levels of shRNA expre
Slide 7: Benitec Pipeline Programs
Benitec Pipeline Programs Early stage clinical Late stage clinical Program Delivery Discovery Preclinical IND-Enabling Commercial Rights (IND – Phase 2) (Phase 2 – Phase 3) Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid • global BB-401 Intratumoral HNSCC ddRNAi • global BB-50
Slide 8: Head and Neck Squamous Cell Carcinoma (HNSCC) Program Update
Head and Neck Squamous Cell Carcinoma (HNSCC) Program Update Early stage clinical Late stage clinical Program Delivery Discovery Preclinical IND-Enabling Commercial Rights (IND – Phase 2) (Phase 2 – Phase 3) Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid • global BB-401 Intra
Slide 9: Head and Neck Squamous Cell Carcinoma (HNSCC)
Head and Neck Squamous Cell Carcinoma (HNSCC) Anatomical sites of HNSCC Incidence and Patient Mortality: • Circa 64,000 patients diagnosed annually in US • 50% of patients expected to develop recurrent or metastatic disease • 13,000 deaths annually in the US • Over 90% of HNSCC lesions overexpress e
Slide 10: BB-401: Expressed Anti-Sense RNA Against EGFR Phase 1 Single Agent Clinical Data
BB-401: Expressed Anti-Sense RNA Against EGFR Phase 1 Single Agent Clinical Data • Phase I study* of 17 patients with advanced, refractory HNSCC • Strong correlation between baseline level of EGFR expression and clinical response • Safety and efficacy evaluated following direct intra-tumoral injecti
Slide 11: BB-401: Follow on Phase 1 Study in Combination with Cetuximab and Radiation
BB-401: Follow on Phase 1 Study of BB-401 in Combination with Cetuximab and Radiation Untreated EFGR-AS Injected Lymph Node Lymph Node • 6 patients were treated in a Phase 1 study of BB-401 in Pre-treatment combination with radiation and cetuximab • 5 of 6 patients experiencing Objective Responses (
Slide 12: Clinical Candidate BB-401: Product Overview
Head & Neck Squamous Cell Carcinoma Clinical Candidate BB-401: Product Overview • Over 50,000 new cases diagnosed in US in 2017, global market estimated at US$1.5 billion in 2024 Head & Neck Squamous • Morbidity caused by spatial effects of tumors in confined anatomical structures of the head and ne
Slide 13: Oculopharyngeal Muscular Dystrophy (OPMD) Program Update
Oculopharyngeal Muscular Dystrophy (OPMD) Program Update Early stage clinical Late stage clinical Program Delivery Discovery Preclinical IND-Enabling Commercial Rights (IND – Phase 2) (Phase 2 – Phase 3) Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid • global BB-401 Intratumo
Slide 14: OPMD Disease Overview
OPMD Disease Overview Disease: • Rare autosomal dominant inheritance • 1:100,000 (Europe) • As high as 1:600 in specific populations • Typical age of onset is in 50’s or 60’s Characterized by: • Eyelid drooping (ptosis) • Swallowing difficulty (dysphagia) • Proximal limb weakness • Death due to aspi
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: • A 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 16: BB-301: 'Silence and Replace' Approach
BB-301: ‘Silence and Replace’ Approach BB-301 ITR Muscle Specific Promoter Codon optimized wildtype PABPN1 PABPN1 shRNA-1 PABPN1 shRNA-2 ITR “Replace” “Silence” Insensitive to shRNA 16
Slide 17: Pre-Clinical Model of OPMD: The 'A17' Mouse
Pre-Clinical Model of OPMD: The ‘A17’ Mouse • Transgenic mouse: express a mutated bovine PABPN1 driven by the human skeletal actin promoter in addition to the endogenous PABPN1 • Recapitulates severe muscle atrophy • Mimics many of the disease pathologies: - Progressive muscle weakness/ atrophy - Fi
Slide 18: BB-301 Treatment Inhibits Diseased Gene Expression & Restores Wildtype PABPN1 Levels
BB-301 Treatment Inhibits Diseased Gene Expression & Restores Wildtype PABPN1 Levels in A17 Mice SILENCE: Inhibition of PABPN1 Expression REPLACE: Codon-Optimized PABPN1 Expression 91% 88% Replacement Inhibition Animal #: 1 2 3 4 5 6 7 8 Animal #: 1 2 3 4 5 6 7 8 A17 + BB-301 A17 + BB-301 A17 + BB-3
Slide 19: Intranuclear Inclusions are Resolved in A17 Mice Treated with BB-301
Intranuclear Inclusions are Resolved in A17 Mice Treated with BB-301 40 *** Wildtype + Saline A17 + Saline *** % Cells PABPN1 Intranuclear Inclusions 30 PABPN1/Laminin/DAPI 20 A17+ BB-301 High Dose A17 + BB-301 Low Dose 10 0 Mouse: WT A17 A17 A17 Treatment: Saline Saline BB-301 BB-301 High Dose Low
Slide 20: BB-301 Treatment Restores Muscle Force and Muscle Weight in A17 Mice
BB-301 Treatment Restores Muscle Force and Muscle Weight in A17 Mice Restoration of Muscle Force Restoration of Muscle Weight 2000 ** ** * 2 ** ** ** ** * ** ** * Muscle Weight/Final Body Weight (mg/g) * Wildtype 1600 * Saline 1.6 A17 BB-301 Low A17 BB-301 High 1200 1.2 Force (mN) A17 Saline 0.8 800
Slide 21: Clinical Candidate BB-301: Product Overview
Oculopharyngeal Muscular Dystrophy Clinical Candidate BB-301: Product Overview Oculopharyngeal • Rare, autosomal dominant, monogenic disease • Estimated 12,000 patients in Western countries Muscular • Eyelid drooping, swallowing difficulties, proximal limb weakness, death due to aspiration pneumonia
Slide 22: Multiple Shots on Goal: Longer Term Milestones 2017-2019
Multiple Shots on Goal Longer Term Milestones 2017-2019 2017 2018 2019 HNSCC BB-401 (EGFR-AS) • IND filing • Phase 2 initiation • Phase 2 completion HNSCC • Discovery BB-501 (ddRNAi EGFR) • IND-enabling studies • Phase 1/2 initiation • Preclinical POC OPMD • IND enabling studies BB-301 • Pre-IND mee
Slide 23: Contact
Contact: David Suhy CSO dsuhy@benitec.com Cliff Holloway CBO/COO cholloway@benitec.com
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