Benitec Biopharma Inc. · NASDAQ:BNTC
Benitec Biopharma — Biotech Showcase 2018
35 slides from Benitec Biopharma's conference presentation, Jan 8, 2018
Slide 1: Biotech Showcase
BIOTECH SHOWCASE NASDAQ: BNTC | ASX: BLT 8 January 2018 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 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 Assets in
Slide 4: Highlights
HIGHLIGHTS EGFR-targeted gene silencing Unique ‘silence and replace’ Other programs targeting retinal Programs advancing therapy entering confirmatory therapeutic designed to treat disorders and infectious disease to clinic Phase II trial in Q1 2018 OPMD anticipated to enter clinic could be clinic-r
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 Decem
Slide 6: Experienced Executive Team
EXPERIENCED EXECUTIVE TEAM Greg West Georgina Kilfoil Chief Executive Officer Chief Clinical and Development • Former CFO of Benitec Biopharma, Operations Officer 10 years biotech experience • Former VP of Clinical Operations, Benitec Biopharma • Prior roles at PriceWaterhouse, Bankers Trust, • Prio
Slide 7: Recent Achievements: Value Creation
Value Creation Near term value inflection points as two programs move into the clinic in 2018 RECENT Additional programs which could be clinic-ready by 2019 ACHIEVEMENTS Flexibility of ddRNAi platform can accelerate clinical And path to value creation and shareholder value with the ability to move p
Slide 8: Recent Achievements
Achievements Nant Capital makes strategic investment in Benitec and brings in Phase II oncology asset EU orphan drug designation for oculopharyngeal muscular dystrophy (OPMD), US application filed Nature Communications publication of initial RECENT ‘silence and replace’ preclinical data (OPMD) Pre-I
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 Phase 1/2a Phase 2 and Program Delivery Discovery Preclinical IND-Enabling Commercial rights studies Phase 3 Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid Global BB-401 Intratumoral HNSCC ddRNAi Global BB-501 Intratumoral Orphan disease - oculopharyn
Slide 11: Benitec Pipeline
BENITEC PIPELINE Phase 1/2a Phase 2 and Program Delivery Discovery Preclinical IND-Enabling Commercial rights studies Phase 3 Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid Global BB-401 Intratumoral HNSCC ddRNAi Global BB-501 Intratumoral Orphan disease - oculopharyngeal mus
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 Comple
Slide 14: BB-401 Follow-on Phase I Study in Combination 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 Head & Neck US: Over 50,000 new cases Morbidity caused by the spatial diagnosed in 2017, global effects of tumors in the Over 90% of HNSCC overexpress Squamous Cell market estimated to be US$1.5 confined anatomical struc
Slide 16: Benitec Pipeline
BENITEC PIPELINE Phase 1/2a Phase 2 and Program Delivery Discovery Preclinical IND-Enabling Commercial rights studies Phase 3 Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid Global BB-401 Intratumoral HNSCC ddRNAi Global BB-501 Intratumoral Orphan disease - oculopharyngeal mus
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 the PABPN1 Gene
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 18
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 19
Slide 21: BB-301 Reverses Intranuclear Inclusions in OPMD Mouse Model
BB-301 REVERSES INTRANUCLEAR INCLUSIONS IN OPMD MOUSE MODEL 20
Slide 22: BB-301 Reverses Fibrosis in Transverse Muscle Sections
BB-301 REVERSES FIBROSIS IN TRANSVERSE MUSCLE SECTIONS IN OPMD MOUSE MODEL
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 Oculopharyngeal Rare, autosomal dominant, Estimated 12,000 effected Eyelid drooping, swallowing heritable monogenic patients in Western countries. difficulties, proximal limb muscular dystrophy weakness, death due to dise
Slide 25: Benitec Pipeline
BENITEC PIPELINE Phase 1/2a Phase 2 and Program Delivery Discovery Preclinical IND-Enabling Commercial rights studies Phase 3 Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid Global BB-401 Intratumoral HNSCC ddRNAi Global BB-501 Intratumoral Orphan disease - oculopharyngeal mus
Slide 26: BB-103 Positions Inhibitory shRNA Across Conserved Sequences in HBV Genome
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 24
Slide 27: BB-103 Builds Upon Learnings from TT-034 First in Man Trial 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 25
Slide 28: PXB Mouse, a Chimeric Animal with a Liver Replaced by Human Hepatocytes
PXB MOUSE, A CHIMERIC ANIMAL WITH A LIVER HIGHLY REPLACED BY HUMAN HEPATOCYTES
Slide 29: In Vivo Infectious Studies Using PXB Mice
IN VIVO INFECTIOUS STUDIES USING PXB MICE 26
Slide 30: Single Dose BB-103 + Entecavir Gives >4 Log Suppression of HBV DNA
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) 27
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 infects HBV viral proteins, especially Need for effective therapies 257 million people resulting in HBsAg causes hepatic that promote the restoration of Hepatitis B (HBV) up to 780,000 deaths per year inflammation, liver dysfu
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 showed • Identified novel viral 401 into clinic in open ‘silence and replace’ significant reductio
Slide 34: Investment Highlights
INVESTMENT HIGHLIGHTS Novel combination of Capital market access Strong in-house gene therapy and gene capabilities silencing • Listed on ASX and • Validated ddRNAi NASDAQ • Scientific operations technology • US shelf registration • Deep gene therapy • Robust pipeline in expertise oncology, orphan g
Slide 35: Contact: info@benitec.com
CONTACT: info@benitec.com NASDAQ: BNTC | ASX: BLT