Benitec Biopharma Inc. · NASDAQ:BNTC
Benitec Biopharma — Rodman & Renshaw Global Investment Conference 2017
39 slides from Benitec Biopharma's conference presentation, September 2017
Slide 1: Path to Value Creation
NASDAQ: BNTC ASX: BLT Path to Value Creation September 2017 Rodman & Renshaw Global Investment Conference
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 "expec
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 Assets in
Slide 4: 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 designed to treat orphan disease oculopharyngeal muscular dys
Slide 5: Permanent Gene Silencing with DNA-Directed RNA Interference (ddRNAi)
Permanent Gene Silencing with 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, steady state levels of shRNA
Slide 6: Diverse Program Pipeline
Diverse Program Pipeline IND-‐ Early stage clinical Late stage clinical Commercial Program Delivery Discovery Preclinical Enabling (IND – Phase 2) (Phase 2 – Phase 3) Rights Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid • global BB-‐401 Intratumoral HNSCC ddRNAi • global B
Slide 7: Recent Achievements and Path to Value Creation
Recent Achievements and Path to Value Creation Value Creation • Near term value inflection points as two programs move into the clinic in 2018 • Multi stage clinical company at the end of 2018 • Flexibility of ddRNAi platform can accelerate clinical and shareholder value with the ability to move pro
Slide 8: 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 • Former SVP of Research & Development, Benitec Biopharma Dr. David Suhy • Prior roles at Tacere Therapeu
Slide 9: Company Financial Snapshot
Company Financial Snapshot Australia US Key Shareholder Details Listed ASX 2002: Listed NASDAQ 2015: BLT BNTC/BNTCW Share Price as of 30 June 2017: (ADR 25:1) A$0.125 US$1.85 (ADS) 52 week high/low as of 30 June 2017 A$0.28/A$0.085 US$5.48 / US$1.2 (ADS) Average daily volume (6 months to 30 June, 20
Slide 10: Head and Neck Squamous Cell Carcinoma (HNSCC) Program Update
Head and Neck Squamous Cell Carcinoma (HNSCC) Program Update IND-‐ Early stage clinical Late stage clinical Commercial Program Delivery Discovery Preclinical Enabling (IND – Phase 2) (Phase 2 – Phase 3) Rights Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid • global BB-‐401
Slide 11: 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 12: 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 • Safety and efficacy evaluated following direct intra-‐tumoral injection weekly for 4 weeks: • 29 % (5 patients) -‐Objective Response • Of these 2 p
Slide 13: BB-401: Follow on Phase 1 Study 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 combination with Pre-‐treatment radiation and cetuximab • 5 of 6 patients experiencing Objective R
Slide 14: Clinical Candidate BB-401: Product Overview
Head & Neck Squamous Cell Carcinoma Clinical Candidate BB-‐401: Product Overview • Over 50,000 new cases diagnosed in the US in 2017, global market Head & Neck estimated to be US$1.5 billion in 2024 Squamous Cell • Morbidity caused by the spatial effects of tumors in the confined Carcinoma anatomic
Slide 15: Oculopharyngeal Muscular Dystrophy (OPMD) Program Update
Oculopharyngeal Muscular Dystrophy (OPMD) Program Update IND-‐ Early stage clinical Late stage clinical Commercial Program Delivery Discovery Preclinical Enabling (IND – Phase 2) (Phase 2 – Phase 3) Rights Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid • global BB-‐401 Intr
Slide 16: 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 17: 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 nucleu
Slide 18: BB-301: 'Silence and Replace' Approach
BB-‐301: ‘Silence and Replace’ Approach AAV • Non-‐integrating, non-‐ BB-‐301 ITR Muscle Specific Codon optimized wildtype 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 almost
Slide 19: 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
Slide 20: 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 A17 Saline BB-‐301 A17 Saline BB-‐301 20
Slide 21: 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 ** ** ** * ** ** 1.8 * ** ** Muscle Weight/Final Body Weight (mg/g) * * * * 1.6 1600 * 1.4 1.2 1200 Force (mN) A17 Saline 1 FVB Saline BB-‐301 High Dose 0.8 800 BB-‐
Slide 22: Clinical Candidate BB-301: Product Overview
Oculopharyngeal Muscular Dystrophy Clinical Candidate BB-‐301: Product Overview • Rare, autosomal dominant, monogenic disease Oculopharyngeal • Estimated 12,000 patients in Western countries Muscular Dystrophy • Characterized by eye lid drooping, swallowing difficulties, proximal limb weakness, dea
Slide 23: Wet Age-Related Macular Degeneration (AMD) Program Update
Wet Age-‐Related Macular Degeneration (AMD) Program Update IND-‐ Early stage clinical Late stage clinical Commercial Program Delivery Discovery Preclinical Enabling (IND – Phase 2) (Phase 2 – Phase 3) Rights Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid • global BB-‐401 I
Slide 24: Wet Age-Related Macular Degeneration (AMD) Disease Overview
Wet Age-‐Related Macular Degeneration (AMD) Disease Overview • Leading cause of irreversible vision loss in U.S. with 196M people affected worldwide by 2020 • Lucentis /Eylea act as a molecular sponges to mop up secreted VEGF-‐a (VEGF-‐b and PlGF) • Although drugs stabilize vision in many, most d
Slide 25: BB-201: Designed to Silence Three Clinically Validated Targets of Ocular Neovascularization
BB-‐201: Designed to Silence Three Clinically Validated Targets of Ocular Neovascularization VEGFb shmiR VEGFa shmiR PlGF shmiR ITR U6-‐9 U6-‐1 U6-‐8 ITR • An AAV-‐encapsidated construct that produces three independent shRNAs, each modeled into a miRNA backbone, to inhibit the expression of VEG
Slide 26: BB-201: In vitro Inhibition of VEGF-a, VEGF-b and PlGF
BB-‐201: In vitro Inhibition of VEGF-‐a, VEGF-‐b and PlGF VEGF-‐a VEGF-‐b PlGF 100 1.0E+05 100 7.0E+05 100 15000 mRNA mRNA mRNA Protein VEGFb-‐sh1 PGF -‐sh7 VEGFa-‐sh8 80 8.0E+04 80 5.6E+05 Anti-‐VEGF-‐b shMir copies / cell anti-‐PlGF shMir copies / cell 80 12000 Anti-‐VEGF-‐a shMir cop
Slide 27: Retina Pigment Epithelia Cells are a Major Source of Secreted VEGF-a in Wet AMD
Retina Pigment Epithelia Cells are a Major Source of Secreted VEGF-‐a in Wet AMD Choroid Bruch’s Membrane neovascularization Secreted VEGF produced Vitreous Humor Lucentis , Avastin, Eylea all target the VEGF-‐a production in the eye 27
Slide 28: Modified AAV Vectors for Intravitreal Delivery
Modified AAV Vectors for Intravitreal Delivery • BB-‐201 is being developed for intravitreal route of delivery • Intravitreal is more commercially viable than a subretinal injection (typically used by most gene therapy vectors for ocular diseases) • Vectors developed through 4DMT’s ‘therapeutic evo
Slide 29: Superior Retinal Transduction Using a Novel AAV Capsid Administered via Intravitreal Injection
Superior Retinal Transduction Using a Novel AAV Capsid Administered via Intravitreal Injection GFP in retina after intravitreal GFP in Baseline retina after intravitreal injection of standard AAV2 capsid injection of novel AAV capsid Day 28 In non human primates 29
Slide 30: Clinical Candidate BB-201: Product Overview
Wet Age-‐Related Macular Degeneration Clinical Candidate BB-‐201: Product Overview • 196m people impacted worldwide by 2020 Wet Age-‐related • Characterized by growth of new blood vessels into the retina as a result Macular of abnormally high levels of proteins from the VEGF family Degeneration •
Slide 31: Hepatitis B (HBV) Program Update
Hepatitis B (HBV) Program Update IND-‐ Early stage clinical Late stage clinical Commercial Program Delivery Discovery Preclinical Enabling (IND – Phase 2) (Phase 2 – Phase 3) Rights Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid • global BB-‐401 Intratumoral HNSCC ddRNAi •
Slide 32: Positioning of shRNA Used in Clinical Construct Ensure Cleavage of Multiple HBV Transcripts
Positioning of shRNA Used in Clinical Construct Ensure Cleavage of Multiple HBV Transcripts HBV proteins HBV genome HBV Transcripts shRNA 4 shRNA 8 shRNA 9 * Sequences selected for shRNA are well conserved across HBV genotypes A-‐H 32
Slide 33: BB-103: An Anti-HBV Agent that Builds in Learning From Benitec's First in Man TT-034
BB-‐103: An Anti-‐HBV Agent that Builds in Learning From Benitec’s First in Man TT-‐034 Trial in HCV AAV REP/CAP removed and replaced with expression cassette TT-034 ITR A shRNA-‐22 B shRNA-‐19 C shRNA-‐6 ITR Recombinant AAV8 - HCV BB-103 ITR A HBV-‐1 B HBV-‐2 C HBV-‐3 ITR Recombinant AA
Slide 34: In Vivo Infectious HBV Studies Using PXB Mice
In Vivo Infectious HBV Studies Using PXB Mice 2. Incubate mice for 4 3. Transduce mice with BB-‐103 weeks, establish baseline HBV infection, randomize Chimeric mouse with HBV infected Chimeric mouse humanized liver 1. Infect chimeric PXB mice 4. Administer Entecavir (Daily) with HBV genotype C 5. F
Slide 35: BB-103 as a Monotherapy and in Combination with Entecavir: Reduction of Serum HBV DNA
BB-‐103 as a Monotherapy and in Combination with Entecavir: Reduction of Serum HBV DNA Levels 1.0E+09 Untreated, HBV infected PXB mice 1.0E+08 Serum HBV DNA (copies/ml) 1.0E+07 1.34 log drop BB-‐103 (*max 2.17 Day 63) * 1.0E+06 2.63 log drop ETV 1.0E+05 LLOQ – 4e4 DNA copies ml (~ 3.72 logs) (HBV
Slide 36: BB-103 in Combination with Entecavir: Reduction of Serum HBsAg Levels
BB-‐103 in Combination with Entecavir: Reduction of Serum HBsAg (S-‐Antigen) Levels 1.0E+04 Untreated, HBV infected PXB mice 1.0E+03 0.46 log drop ETV Serum HBs Ag (IU/ml) 1.0E+02 2.14 log drop BB-‐103 + ETV 1.0E+01 Entecavir (ETV) administered daily 0 7 14 21 28 35 42 49 56 63 70 77 84 91 Day 36
Slide 37: A Summary of Anti-viral Activity of BB-103 as a Monotherapy or in Combination with Entecavir
A Summary of Anti-‐viral Activity of BB-‐103 as a Monotherapy or in Combination with Entecavir Log Reduction of Log Reduction Log Reduction Treatment Serum HBV DNA of HBsAg of HBeAg entecavir (ETV) Control groups 2.63 0.46 0.37 6 mg/kg daily Single administration BB-‐103 2.17 max 1.94 max 1.61 ma
Slide 38: Hepatitis B Clinical Candidate BB-103: Product Overview
Hepatitis B Clinical Candidate BB-‐103: Product Overview • An estimated 257 million people with HBV infection Hepatitis B • Need for safe and effective therapies that promote the restoration of a host immune response through targeted HBsAg knockdown • Designed as a single dose treatment to be added
Slide 39: Contact
Contact: Greg West CEO gwest@benitec.com David Suhy CSO dsuhy@benitec.com Cliff Holloway CBO/COO cholloway@benitec.com
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