Benitec Biopharma Inc. · NASDAQ:BNTC
Benitec Biopharma — BIO 2018
42 slides from Benitec Biopharma's conference presentation, May 28, 2018
Slide 1: Pathway to Value Creation
PATHWAY TO VALUE CREATION NASDAQ: BNTC | ASX: BLT BIO Corporate Presentation 28 May 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 Proven Technology First company into human clinical studies under a US IND with systemically delivered non- withdrawable RNAi (TT-034) Benitec has created a novel combination of gene Robust Pipeline therapy and gene silencing Assets in oncology (Phase 2 entry, 1Q18), to change trea
Slide 4: Highlights
HIGHLIGHTS EGFR-targeted gene Unique ‘silence and replace’ Other programs could be Programs silencing therapy therapeutic designed to treat clinic-ready in late 2019 advancing to clinic confirmatory Phase 2 trial OPMD with IND filing in Q1 initiated in Q1 2018 2019 Listed on ASX (2002, BLT) US$50M c
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 March, 2018: (ADS ratio 20:1) A$0.20 US$3.18 52 week high/low as of 31st March, 2018 A$0.33/A$0.11 US$5.48 / US$1.85 (ADS) Average daily volume (6 months to 31st March,
Slide 6: Experienced Executive Team
EXPERIENCED EXECUTIVE TEAM Greg West Bryan Dulhunty Chief Executive Officer Chief Financial Officer • Former CFO of Benitec Biopharma • Chairman of ASX listed Cryosite Ltd • Prior roles as NED, CEO, CFO at a number of • Former Executive Chairman, Viralytics public companies • Prior roles as NED, MD,
Slide 7: Value Drivers
Value Drivers One year major value inflection points include initial data readout from Phase 2 oncology study and entry into the clinic with OPMD asset (BB-301) Additional programs could be clinic-ready in late 2019 VALUE DRIVERS And path to value creation Flexibility of ddRNAi platform can potentia
Slide 8: Recent Achievements
Achievements Nant Capital makes strategic investment in Benitec to bring in Phase 2 oncology asset (BB-401) Phase 2 clinical study of BB-401 in head & neck squamous cell carcinoma (HNSCC) US and EU orphan drug designation for RECENT oculopharyngeal muscular dystrophy (OPMD) ACHIEVEMENTS Nature Commu
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 Simul
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) Incidence and Patient Mortality: Anatomical sites of HNSCC • Global incidence of 119,000 in 2016 expected to increase to over 136,000 in 2026 • 50% of patients expected to develop recurrent or metastatic disease • Median overall survival of 7.8 months and
Slide 13: Phase 1 Single Agent Clinical Data
BB-401: EXPRESSED ANTI-SENSE RNA AGAINST EGFR PHASE 1 SINGLE AGENT CLINICAL DATA • BB-401 is comprised of plasmid DNA which produces a 39-nt antisense RNA with specificity against EGFR • Phase I study of 17 patients with advanced, refractory HNSCC • Safety and efficacy following direct intra-tumoral
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 experienced an Objective Response (83%) • 4
Slide 15: BB-401-01: Phase 2 Clinical Study in HNSCC
BB-401-01: PHASE 2 CLINICAL STUDY IN HNSCC Intratumoral BB-401 in patients with recurrent or metastatic head and neck squamous cell carcinoma Multi Center Single Arm Study Endpoints after 2 cycles of BB-401 Key Entry Criteria Fleming 2 Stage Design (1 cycle = 4 weekly injections BB-401) • Histologic
Slide 16: Head & Neck Squamous Cell Carcinoma: BB-401 Product Overview
HEAD & NECK SQUAMOUS CELL CARCINOMA Clinical Candidate BB-401: Product Overview Incidence to increase from Morbidity caused by the Over 90% of HNSCC Head & Neck 119,000 in 2016 to 136,000 spatial effects of tumors in overexpress EGFR Squamous Cell in 2026 with global market the confined anatomical C
Slide 17: 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 18: 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 late 40’s or older Characterized by: • Eyelid drooping (ptosis) • Swallowing difficulty (dysphagia) • Proximal limb weakness • Death due to a
Slide 19: Tissue and Molecular Aspects of OPMD
TISSUE AND MOLECULAR ASPECTS OF OPMD Histopathology: Affected Non-Affected • Decrease of muscle fiber number • Variation in the size of muscle fibers • Fibrosis (connective tissue) • Net effect: decrease in muscle force PABPN1: • A ubiquitous factor that promotes interaction between the poly(A) poly
Slide 20: BB-301: A 'Silence and Replace' Based Approach
BB-301: A ‘SILENCE AND REPLACE’ BASED APPROACH Modified AAV9 AAV • Non-integrating, non-pathogenic viral delivery • To date, AAV has been used in BB-301 ITR Muscle Specific REP/CAP removed and Codon replacedoptimized wildtype with expression PABPN1 cassette PABPN1 PABPN1 ITR over 204 clinical trials
Slide 21: 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 Intra Nuclear Fibrosis Muscle Force Muscle W
Slide 22: BB-301: Expression of shRNA in TA Muscles of A17 Mice
BB-301: EXPRESSION OF SHRNA IN TA MUSCLES OF A17 MICE ~ 2,400,000 shRNA-2 ~ 1,700,000 shRNA-1 ~ 650,000 shRNA-2 ~ 530,000 shRNA-1 ~ 25,000 shRNA-2 ~ 22,000 shRNA-1 ~ 17,000 shRNA-2 ~ 14,000 shRNA-1 ~ 2,600 shRNA-2 ~ 2,400 shRNA-1 shRNA measured 14 weeks post BB-301 dosing Group AVG Group AVG Group A
Slide 23: BB-301 Silences PABPN1 Expression in an OPMD Mouse Model
BB-301 SILENCES PABPN1 EXPRESSION (INCLUDING MUTANT PABPN1) IN AN OPMD MOUSE MODEL 86% inhibition 75% inhibition 31% inhibition 32% inhibition PABPN-1 Inhibition measured 14 weeks post BB-301 dosing 14% inhibition Group AVG Group AVG Group AVG Group AVG Group AVG Group AVG Group AVG A17 Saline 7.5e1
Slide 24: BB-301 Restores Normal PABPN1 Levels in A17 Mouse Model
BB-301 RESTORES NORMAL PABPN1 LEVELS IN A17 MOUSE MODEL 63% 26% Codon Optimized PABPN-1 expression measured 14 weeks post BB-301 dosing 2% 1% Group AVG Group AVG Group AVG Group AVG Group AVG Group AVG Group AVG A17 Saline 7.5e11 vg/ 2.5e11 vg/ 5e10 vg/ 1e10 vg/ 2e9 vg/ 4e8 vg/ Control muscle muscle
Slide 25: BB-301 Reverses Intranuclear Inclusions in A17 Mouse Model
BB-301 REVERSES INTRANUCLEAR INCLUSIONS IN A17 MOUSE MODEL 7.5e11 vg/muscle 2.5e11 vg/muscle 5e10 vg/muscle 1e10 vg/muscle 2e9 vg/muscle 4e8 vg/muscle A17 - Saline wildtype- saline 2e9 vg/muscle 4e8 vg/muscle 5e10 vg/muscle 1e10 vg/muscle 7.5e11 vg/muscle 2.5e11 vg/muscle INI persistence measured 14
Slide 26: BB-301 Restores Muscle Force in OPMD Mouse Model
BB-301 RESTORES MUSCLE FORCE IN OPMD MOUSE MODEL Unpaired t-test “Silence” “Replace” compared to A17 saline BB-301 Inhibition WT-PABPN1 Dose (vg) PABPN1* Expression 7.5e11 86 % 63 % 2.5e11 75 % 26 % 5e10 31 % 2% 1e10 32 % 1% 2e9 14 % 0% 4e8 0% 0% Dose BB-301 Force measured 14 weeks post BB-301 dosin
Slide 27: BB-301: Restoration of Muscle Function Takes Time
BB-301: RESTORATION OF MUSCLE FUNCTION TAKES TIME 14 weeks post BB-301 Dosing 20 weeks post BB-301 Dosing BB-301 Dose Inhibition WT-PABPN1 (vg) PABPN1* Expression 6e10 88 % 91 % 1e10 63 % 13 % 27
Slide 28: BB-301: Scalable Manufacturing
BB-301: SCALABLE MANUFACTURING • Produced with scalable baculovirus based methodologies and Silver stain of SDS protein gel purification processes to control cost of goods. showing output of purification steps (3 capsid bands expected in final product) • Using a modified AAV capsid for the generatio
Slide 29: BB-301-01: Phase 1/2a Clinical Study in OPMD
BB-301-01: PHASE 1/2A CLINICAL STUDY IN OPMD Intramuscular BB-301 in OPMD patients with swallowing dysfunction* Endpoints Key Entry Criteria Multicenter Dose Escalation Study Through 52 Weeks • Aged 35 to 80 Cohort 1 – Low Dose • Safety & tolerability • Clinical diagnosis of OPMD (~3-5 BB-301) • Qua
Slide 30: OPMD: Key Features in BB-301 Development
OPMD: KEY FEATURES IN BB-301 DEVELOPMENT Non-Clinical: Regulatory: • OPMD phenotypes (muscle strength, dystrophy, • Orphan Drug Designation granted in EU (2017) and US intranuclear inclusions, fibrosis) in A17 mice are (2018) which can lower cost of approval, potentially reduce reversible developmen
Slide 31: 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 32: 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 33: BB-103 Positions Inhibitory shRNA Across Well 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 33
Slide 34: BB-103 Builds Upon Learnings from 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 34
Slide 35: PXB Mouse, a Chimeric Animal with a Liver Highly Replaced by Human Hepatocytes
PXB MOUSE, A CHIMERIC ANIMAL WITH A LIVER HIGHLY REPLACED BY HUMAN HEPATOCYTES 35
Slide 36: In Vivo Infectious Studies Using PXB Mice
IN VIVO INFECTIOUS STUDIES USING PXB MICE 36
Slide 37: 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) 37
Slide 38: 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 39: 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 40: 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) entered clinic in 1Q18 ‘silence and replace’ significant redu
Slide 41: Investment Highlights
INVESTMENT HIGHLIGHTS Novel combination of gene Capital market access Strong in-house capabilities therapy and gene silencing • BB-401 (oncology) in clinic • Listed on ASX (BLT) and • Deep gene therapy expertise with Phase 2 study. BB-301 NASDAQ (BNTC) (OPMD) in clinic early 2019 • In-house manufact
Slide 42: Contact: info@benitec.com
CONTACT: info@benitec.com NASDAQ: BNTC | ASX: BLT