Benitec Biopharma Inc. · NASDAQ:BNTC
Benitec Biopharma — 30th Annual Roth Conference (March 2018)
35 slides from Benitec Biopharma's conference presentation, Mar 13, 2018
Slide 1: Pathway to Value Creation
PATHWAY TO VALUE CREATION NASDAQ: BNTC | ASX: BLT 30th Annual Roth Conference 13 March 2018 Greg West, Chief Executive 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 Proven Technology First company into human clinical studies under a US IND with systemically delivered non- Benitec has created a novel withdrawable RNAi (TT-034) combination of gene therapy and gene silencing Robust Pipeline to change
Slide 4: Highlights
HIGHLIGHTS EGFR-targeted gene Unique ‘silence and replace’ Other programs could be Programs silencing therapy entering therapeutic designed to treat clinic-ready in 2019 advancing to clinic confirmatory Phase 2 trial in OPMD anticipated to enter Q1 2018 clinic Q4 2018 Listed on ASX (2002) US$50m cap
Slide 5: Corporate Snapshot
CORPORATE SNAPSHOT AUSTRALIA US KEY SHAREHOLDER DETAILS Listed ASX 2002: BLT Listed NASDAQ 2015: BNTC/BNTCW Share Price as of 31st December, 2017: (ADR 25:1) A$0.20 US$2.96 52 week high/low as of 31st December, 2017 A$0.28/A$0.105 US$5.48 / US$1.39 (ADS) Average daily volume (6 months to 31st Decemb
Slide 6: Experienced Executive Team
EXPERIENCED EXECUTIVE TEAM Greg West Georgina Kilfoil Chief Executive Officer Chief Development Officer • Former CFO of Benitec Biopharma • Former VP of Clinical Operations, Benitec • Prior roles as NED, CEO, CFO at a number of Biopharma public companies • Prior roles at Anthera Pharmaceuticals, InC
Slide 7: Value Drivers
Value Drivers Near term value inflection points as two programs move into the clinic in 2018 Additional programs could be clinic-ready in 2019 VALUE DRIVERS And path to value creation Flexibility of ddRNAi platform can accelerate clinical and shareholder value with the ability to move proven ddRNAi
Slide 8: Recent Achievements
Achievements Nant Capital makes strategic investment in Benitec and brings in Phase 2 oncology asset US and EU orphan drug designation for oculopharyngeal muscular dystrophy (OPMD) Nature Communications publication of initial RECENT ‘silence and replace’ preclinical data (OPMD) Pre-IND meeting with
Slide 9: Permanent Gene Silencing
PERMANENT GENE SILENCING With 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 multiple genes simultaneously Simult
Slide 10: Diverse Program Pipeline
DIVERSE PROGRAM PIPELINE Early stage clinical Late stage clinical Program Delivery Discovery Preclinical IND-Enabling Commercial rights (IND – Ph 2) (Ph 2 – Ph 3) Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid Global BB-401 Intratumoral HNSCC ddRNAi Global BB-501 Intratumoral
Slide 11: Benitec Pipeline
BENITEC PIPELINE Early stage clinical Late stage clinical Program Delivery Discovery Preclinical IND-Enabling Commercial rights (IND – Ph 2) (Ph 2 – Ph 3) Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid Global BB-401 Intratumoral HNSCC ddRNAi Global BB-501 Intratumoral Orphan
Slide 12: Head and Neck Squamous Cell Carcinoma (HNSCC)
HEAD AND NECK SQUAMOUS CELL CARINOMA (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 ep
Slide 13: 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 • Safety and efficacy following direct intra-tumoral injection weekly for 4 weeks: • 29 % (5 patients) - Objective Response • 2 patients experienced Complet
Slide 14: BB-401 Follow-on Phase I Study with Cetuximab and Radiation
BB-401: FOLLOW-ON PHASE I STUDY 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 (83%) • 4 p
Slide 15: Head & Neck Squamous Cell Carcinoma: BB-401 Product Overview
HEAD & NECK SQUAMOUS CELL CARCINOMA Clinical Candidate BB-401: Product Overview US: Over 50,000 new cases Morbidity caused by the Over 90% of HNSCC Head & Neck diagnosed in 2017, global spatial effects of tumors in overexpress EGFR Squamous Cell market estimated to be the confined anatomical Carcino
Slide 16: Benitec Pipeline
BENITEC PIPELINE Early stage clinical Late stage clinical Program Delivery Discovery Preclinical IND-Enabling Commercial rights (IND – Ph 2) (Ph 2 – Ph 3) Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid Global BB-401 Intratumoral HNSCC ddRNAi Global BB-501 Intratumoral Orphan
Slide 17: 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 18: Genetic Basis of OPMD: Poly-alanine Expansion in PABPN1
GENETIC BASIS OF OPMD: POLY-ALANINE EXPANSION IN THE PABPN1 GENE 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, and alt
Slide 19: BB-301: A 'Silence and Replace' Based Approach
BB-301: A ‘SILENCE AND REPLACE’ BASED APPROACH AAV • Non-integrating, non-pathogenic viral delivery • To date, AAV has been used in almost 200 clinical trials • Sustained expression (years) following single injection Insensitive to shRNA 19
Slide 20: BB-301 Silences Mutant PABPN1 and Restores Normal PABPN1 in Mouse Model
BB-301 SILENCES MUTANT PABPN1 EXPRESSION AND RESTORES NORMAL PABPN1 IN OPMD MOUSE MODEL 20
Slide 21: BB-301 Reverses Intranuclear Inclusions in OPMD Mouse Model
BB-301 REVERSES INTRANUCLEAR INCLUSIONS IN OPMD MOUSE MODEL *** p ≤ 0.001 21
Slide 22: BB-301 Reverses Fibrosis in Transverse Muscle Sections
BB-301 REVERSES FIBROSIS IN TRANSVERSE MUSCLE SECTIONS IN OPMD MOUSE MODEL 22
Slide 23: BB-301 Restores Muscle Function in OPMD Mouse Model
BB-301 RESTORES MUSCLE FUNCTION IN OPMD MOUSE MODEL Restoration of Muscle Force Restoration of Muscle Weight 2000 2 ** ** * ** ** ** ** ** * ** * * 1.6 1600 * Muscle weight/final body weight (mg/g) Wildtype/Normal Saline A17 - treated w/ BB-301 Low Dose A17 - treated w/ BB-301 High Dose 1.2 1200 For
Slide 24: Oculopharyngeal Muscular Dystrophy: BB-301 Product Overview
OCULOPHARYNGEAL MUSCULAR DYSTROPHY Clinical Candidate BB-301: Product Overview Rare, autosomal dominant, Estimated 12,000 effected Eyelid drooping, swallowing Oculopharyngeal heritable monogenic patients in Western difficulties, proximal limb muscular disease countries. weakness, death due to dystro
Slide 25: Benitec Pipeline
BENITEC PIPELINE Early stage clinical Late stage clinical Program Delivery Discovery Preclinical IND-Enabling Commercial rights (IND – Ph 2) (Ph 2 – Ph 3) Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid Global BB-401 Intratumoral HNSCC ddRNAi Global BB-501 Intratumoral Orphan
Slide 26: BB-103 Positions Inhibitory shRNA Across Conserved HBV Sequences
BB-103 POSITIONS INHIBITORY shRNA ACROSS WELL CONSERVED SEQUENCES IN THE HBV GENOME HBV proteins HBV genome HBV Transcripts shRNA 4 shRNA 8 shRNA 9 * Sequences selected for shRNA are well conserved across HBV genotypes A-H 26
Slide 27: BB-103 Builds Upon First in Man Trial with TT-034 in HCV
BB-103 BUILDS UPON THE LEARNINGS FROM BENITEC’S FIRST IN MAN TRIAL WITH TT-034 IN HCV Safety and Efficacy Study in Single Doses of TT-034 in Patients with Chronic Hepatitis C Clinical Trials.gov Identifier: NCT10899092 27
Slide 28: PXB Mouse, a Chimeric Animal with Human Hepatocyte Liver
PXB MOUSE, A CHIMERIC ANIMAL WITH A LIVER HIGHLY REPLACED BY HUMAN HEPATOCYTES 28
Slide 29: In Vivo Infectious Studies Using PXB Mice
IN VIVO INFECTIOUS STUDIES USING PXB MICE 29
Slide 30: BB-103 + Entecavir: >4 Log Suppression of HBV DNA and >2 Log HBsAg
A SINGLE DOSE OF BB-103 + DAILY ENTECAVIR RESULTS IN >4 LOG SUPPRESSION OF HBV DNA AND >2 LOG HBsAg Reduction in HBV serum DNA Reduction in HBsAg (s-antigen) 30
Slide 31: BB-103 + Entecavir Reduces HBV Viral RNA by >99%
BB-103 + ENTECAVIR REDUCES HBV VIRAL RNA BY > 99% Reads Normalized to RNA Length (per 1kb) Total HBV Reads PreS1/S2 mRNA (per 1M reads) pgRNA (3.5Kb) (2.4/2.1 Kb) X RNA (0.7kb) Untreated RNA-1 1674 435 171 112 BB-101 RNA-2 457 119 45 31 BB-101+ETV RNA-3 72 19 8 5 BB-103 RNA-4 122 30 12 9 RNA-5 BB-10
Slide 32: Hepatitis B: BB-103 Product Overview
HEPATITIS B Clinical Candidate BB-103: Product Overview WHO estimates HBV HBV viral proteins, Need for effective therapies infects 257 million people especially HBsAg causes that promote restoration of Hepatitis B (HBV) resulting in up to 780,000 hepatic inflammation, liver a host immune response de
Slide 33: Program Summary
PROGRAM SUMMARY BB-401: BB-301: BB-103: BB-201: Oncology (HNSCC) Orphan disease (OPMD) Infectious disease (HBV) Retinal disease (AMD) • EGFR antisense asset (BB- • Unique single vector • Preclinical POC with • Novel viral capsids for 401) moving into clinic in ‘silence and replace’ significant reduc
Slide 34: Investment Highlights
INVESTMENT HIGHLIGHTS Novel combination of gene Capital market access Strong in-house capabilities therapy and gene silencing • Two programs in clinic by the • Listed on ASX and NASDAQ • Scientific operations end of 2018 • US shelf registration • Deep gene therapy expertise • Validated ddRNAi techno
Slide 35: Contact: info@benitec.com
CONTACT: info@benitec.com NASDAQ: BNTC | ASX: BLT
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