Full Press Release Details
BB-301 February 2021 Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 1 www.benitec.comExhibit 99.1 Interim Results of IND-Enabling Large Animal Study for BB-301 February 2021 Copyright Benitec Biopharma Inc
Copyright Benitec Biopharma Ltd 1 www.benitec.com
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, intends, hopes,
anticipates, believes, could, may, evidences and estimates, and other similar expressions, but these words are not the exclusive means of identifying such statements. Such statements include, but are not limited to, any statements relating to
Benitec's pipeline of ddRNAi-based therapeutics, including the initiation, progress and outcomes of clinical trials and any other statements that are not historical facts. Such forward-looking statements involve risks and uncertainties, including,
but not limited to, risks and uncertainties relating to the difficulties or delays in our plans to develop and potentially commercialize our product candidates, the timing of the initiation and completion of preclinical and clinical trials, the
timing of patient enrolment and dosing in clinical trials, the timing of expected regulatory filings, the clinical utility and potential attributes and benefits of ddRNAi and our product candidates, potential future out-licenses and collaborations,
our intellectual property position and duration of our patent portfolio, the ability to procure additional sources of financing and other risks detailed from time to time in filings that Benitec makes with US Securities and Exchange Commission,
including our most recent annual report on Form 20-F and our reports on Form 6-K. Such statements are based on management's current expectations, but actual results may differ materially due to various factors, including those risks and
uncertainties mentioned or referred to in this presentation. Accordingly, you should not rely on those forward-looking statements as a prediction of actual future results. Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd
2 www.benitec.comSafe 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, intends, hopes, anticipates, believes, could, may, evidences and estimates, and other similar expressions, but these words are not the exclusive means of identifying such statements.
Such statements include, but are not limited to, any statements relating to Benitec's pipeline of ddRNAi-based therapeutics, including the initiation, progress and outcomes of clinical trials and any other statements that are not historical facts.
Such forward-looking statements involve risks and uncertainties, including, but not limited to, risks and uncertainties relating to the difficulties or delays in our plans to develop and potentially commercialize our product candidates, the timing
of the initiation and completion of preclinical and clinical trials, the timing of patient enrolment and dosing in clinical trials, the timing of expected regulatory filings, the clinical utility and potential attributes and benefits of ddRNAi and
our product candidates, potential future out-licenses and collaborations, our intellectual property position and duration of our patent portfolio, the ability to procure additional sources of financing and other risks detailed from time to time in
filings that Benitec makes with US Securities and Exchange Commission, including our most recent annual report on Form 20-F and our reports on Form 6-K. Such statements are based on management's current expectations, but actual results may differ
materially due to various factors, including those risks and uncertainties mentioned or referred to in this presentation. Accordingly, you should not rely on those forward-looking statements as a prediction of actual future results. Copyright
Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 2 www.benitec.com
Gene Silencing: A Validated Approach to the Treatment of Some Genetic
Diseases Mutation of a single gene can cause a chronic disease via the resulting intracellular production of a disease- causing protein (i.e. an abnormal form of the protein of interest) Genetic disorders of this type can often be
treated exclusively by "silencing" the intracellular production of the disease-causing protein through well-validated biological approaches like RNA interference ("RNAi") - RNAi employs small nucleic acid molecules to
activate an intracellular enzyme complex, and this biological pathway temporarily reduces the production of the disease-causing protein - In the absence of the disease-causing protein, normal cellular function is restored, and the chronic
disease improves or resolves However, many genetic disorders are not amenable to gene silencing approaches, as the diseased cells produce a mixture of the normal protein of interest and the disease-causing variant of the protein, and the
underlying genetic mutation does not allow for selective targeting of the disease-causing variant - In these cases it is impossible to exclusively silence the disease-causing protein without simultaneously silencing the normal intracellular
protein of interest whose presence is vital to normal cellular functions Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 3 www.benitec.comGene Silencing: A Validated Approach to the Treatment of Some Genetic Diseases
Mutation of a single gene can cause a chronic disease via the resulting intracellular production of a disease- causing protein (i.e. an abnormal form of the protein of interest) Genetic disorders of this type can often be treated
exclusively by "silencing" the intracellular production of the disease-causing protein through well-validated biological approaches like RNA interference ("RNAi") - RNAi employs small nucleic acid molecules to activate
an intracellular enzyme complex, and this biological pathway temporarily reduces the production of the disease-causing protein - In the absence of the disease-causing protein, normal cellular function is restored, and the chronic disease
improves or resolves However, many genetic disorders are not amenable to gene silencing approaches, as the diseased cells produce a mixture of the normal protein of interest and the disease-causing variant of the protein, and the underlying
genetic mutation does not allow for selective targeting of the disease-causing variant - In these cases it is impossible to exclusively silence the disease-causing protein without simultaneously silencing the normal intracellular protein of
interest whose presence is vital to normal cellular functions Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 3 www.benitec.com
"Silence and Replace": Permanent Gene Silencing and
Tissue-Specific Restoration of Biological Function Our proprietary DNA-directed RNA interference (ddRNAi) platform combines RNAi with classical AAV-based gene therapy Through the use of the ddRNAi platform Benitec creates genetic
medicines that, following a single administration, will enable target tissues to perpetually produce siRNA molecules which facilitate the sustained silencing of disease-causing genes Importantly, the ddRNAi platform also allows for
concomitant delivery of wild type replacement genes, and these distinct genetic elements work in concert to silence the expression of disease-causing mutant genes and to simultaneously replace the mutant genes with normal (wild type) genes to
restore the natural underlying physiology of the diseased tissues BB-301, the most advanced genetic medicine currently under development by Benitec, employs this "Silence and Replace" approach for the treatment of Oculopharyngeal
Muscular Dystrophy (OPMD) Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 4 www.benitec.com"Silence and Replace": Permanent Gene Silencing and Tissue-Specific Restoration of Biological Function Our
proprietary DNA-directed RNA interference (ddRNAi) platform combines RNAi with classical AAV-based gene therapy Through the use of the ddRNAi platform Benitec creates genetic medicines that, following a single administration, will enable
target tissues to perpetually produce siRNA molecules which facilitate the sustained silencing of disease-causing genes Importantly, the ddRNAi platform also allows for concomitant delivery of wild type replacement genes, and these distinct
genetic elements work in concert to silence the expression of disease-causing mutant genes and to simultaneously replace the mutant genes with normal (wild type) genes to restore the natural underlying physiology of the diseased tissues
BB-301, the most advanced genetic medicine currently under development by Benitec, employs this "Silence and Replace" approach for the treatment of Oculopharyngeal Muscular Dystrophy (OPMD) Copyright Benitec Biopharma Inc
Copyright Benitec Biopharma Ltd 4 www.benitec.com
Platform Enables Gene Therapy and Permanent Gene Silencing: DNA-Directed
RNA Interference (ddRNAi) Transient gene silencing - siRNA Permanent gene silencing - 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 Simultaneous silencing of disease-causing genes and co-expression of normal genes to restore biological function Copyright
Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 5 www.benitec.comPlatform Enables Gene Therapy and Permanent Gene Silencing: DNA-Directed RNA Interference (ddRNAi) Transient gene silencing - siRNA Permanent gene silencing - 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 Simultaneous silencing of disease-causing genes and co-expression of normal genes to restore biological function Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 5 www.benitec.com
BB-301 for Oculopharyngeal Muscular Dystrophy LATE-STAGE
NON-CLINICAL ASSET WITH CATEGORY-LEADING BIOLOGICAL EFFICACY GLOBAL PREVALENCE OF OPMD EXCEEDS 15,000 PATIENTS AND COMMERCIAL OPPORTUNITY EXCEEDS $1 BILLION OVER THE LIFE OF THE PRODUCT Copyright Benitec Biopharma Inc Copyright
Benitec Biopharma Ltd 6 www.benitec.comBB-301 for Oculopharyngeal Muscular Dystrophy LATE-STAGE NON-CLINICAL ASSET WITH CATEGORY-LEADING BIOLOGICAL EFFICACY GLOBAL PREVALENCE OF OPMD EXCEEDS 15,000 PATIENTS AND COMMERCIAL OPPORTUNITY
EXCEEDS $1 BILLION OVER THE LIFE OF THE PRODUCT Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 6 www.benitec.com
Oculopharyngeal Muscular Dystrophy Lead Candidate BB-301: Product
Overview Rare, autosomal dominant, monogenic disease Oculopharyngeal Estimated prevalence of 15,000 patients in Western countries Muscular Characterized by eyelid drooping, swallowing difficulties, proximal limb Dystrophy
weakness, death due to aspiration pneumonia and malnutrition Designed to treat dysphagia associated with OPMD Silence and Replace' represents a unique gene therapy mechanism BB-301 Product Silence':
Inhibits mutant and wildtype PABPN1 gene expression Profile/Milestones Replace': Simultaneously reintroduces normal PABPN1 gene to restore function Clinical trial to begin enrollment over the next 18-to-22 months
Orphan Drug Designation received in the US and EU provides commercial exclusivity and expeditious development path Value / Commercial scale manufacturing process has been optimized and reproducibly Commercial executed Opportunity
Commercial opportunity in excess of $1 billion over the life of the product Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 7 www.benitec.comOculopharyngeal Muscular Dystrophy Lead Candidate BB-301: Product Overview
Rare, autosomal dominant, monogenic disease Oculopharyngeal Estimated prevalence of 15,000 patients in Western countries Muscular Characterized by eyelid drooping, swallowing difficulties, proximal limb Dystrophy weakness,
death due to aspiration pneumonia and malnutrition Designed to treat dysphagia associated with OPMD Silence and Replace' represents a unique gene therapy mechanism BB-301 Product Silence': Inhibits
mutant and wildtype PABPN1 gene expression Profile/Milestones Replace': Simultaneously reintroduces normal PABPN1 gene to restore function Clinical trial to begin enrollment over the next 18-to-22 months Orphan
Drug Designation received in the US and EU provides commercial exclusivity and expeditious development path Value / Commercial scale manufacturing process has been optimized and reproducibly Commercial executed Opportunity Commercial
opportunity in excess of $1 billion over the life of the product Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 7 www.benitec.com
Genetic Basis of OPMD: Expansion of the Poly-Alanine Tract Within PABPN1
PABPN1: 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 alternative
poly(A) site usage In OPMD: Genetic mutation results in trinucleotide repeat expansion within exon 1 of PABPN1 and results in an expanded poly-alanine tract at the N-terminal end of PABPN1 Non-affected Mutation generates a protein
with an N-terminal expanded poly- alanine tract of up to 18 contiguous alanine residues prone to form aggregates called intranuclear inclusions (INIs) INIs that also sequester wild type PABPN1 could contribute to the "loss of
function" phenotype associated with OPMD Affected WT ATG (GCG) -------------(GCA) GCG GGG GCT GCG.. 6 3 MUT ATG (GCG) (GCG) (GCA) GCG GGG GCT GCG -- 6 1-7 3 Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 8
www.benitec.comGenetic Basis of OPMD: Expansion of the Poly-Alanine Tract Within PABPN1 PABPN1: 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 alternative poly(A) site usage In OPMD: Genetic mutation results in trinucleotide repeat expansion within exon 1 of PABPN1 and results in an expanded poly-alanine
tract at the N-terminal end of PABPN1 Non-affected Mutation generates a protein with an N-terminal expanded poly- alanine tract of up to 18 contiguous alanine residues prone to form aggregates called intranuclear inclusions (INIs)
INIs that also sequester wild type PABPN1 could contribute to the "loss of function" phenotype associated with OPMD Affected WT ATG (GCG) -------------(GCA) GCG GGG GCT GCG.. 6 3 MUT ATG (GCG) (GCG) (GCA) GCG GGG GCT GCG -- 6 1-7 3
Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 8 www.benitec.com
BB-301: Single-Vector "Silence and Replace" Approach AAV
Non-integrating, non- PABPN1 Muscle Specific PABPN1 pathogenic viral delivery Codon optimized wild type PABPN1 ITR ITR BB-301 shRNA-2 Promoter shRNA-1 REP/CAP removed and To date, AAV has been used replaced with expression cassette
in almost 200 clinical trials Sustained expression (years) following single injection "Silence" "Replace" Insensitive to shRNA Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 9
www.benitec.comBB-301: Single-Vector "Silence and Replace" Approach AAV Non-integrating, non- PABPN1 Muscle Specific PABPN1 pathogenic viral delivery Codon optimized wild type PABPN1 ITR ITR BB-301 shRNA-2 Promoter shRNA-1
REP/CAP removed and To date, AAV has been used replaced with expression cassette in almost 200 clinical trials Sustained expression (years) following single injection "Silence" "Replace" Insensitive to shRNA
Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 9 www.benitec.com
IND-Enabling Studies for BB-301 to be Completed Over the Next 12-to-18
Months The IND-enabling non-clinical studies outlined below are being carried out under the guidance of the scientific team at Benitec in close collaboration with a team of Thought Leaders in both medicine and surgery that have been deeply
engaged in the treatment of OPMD patients for several decades 8-week Pilot Dosing study in Beagle dogs to confirm the transduction efficiency of BB-301 following direct intramuscular injection into the pharyngeal muscles via the use of an
open surgical approach (Beagle dog dosing has been completed in this study, and tissue analyses are currently ongoing) - Direct injection of BB-301 into the tibialis anterior muscle of A17 mice achieved robust transduction of the targeted
skeletal muscle cells - This follow-up study in Beagle dogs is being conducted to optimize the proprietary dosing and surgical administration procedures for BB-301 injection into the pharyngeal muscle tissues that underlie the morbidity and
mortality of OPMD and to refine the core analytical methods employed following the completion of dosing 12-week GLP Toxicology and Biodistribution study in Beagle dogs Copyright Benitec Biopharma Inc Copyright Benitec Biopharma
Ltd 10 www.benitec.comIND-Enabling Studies for BB-301 to be Completed Over the Next 12-to-18 Months The IND-enabling non-clinical studies outlined below are being carried out under the guidance of the scientific team at Benitec in close
collaboration with a team of Thought Leaders in both medicine and surgery that have been deeply engaged in the treatment of OPMD patients for several decades 8-week Pilot Dosing study in Beagle dogs to confirm the transduction efficiency of
BB-301 following direct intramuscular injection into the pharyngeal muscles via the use of an open surgical approach (Beagle dog dosing has been completed in this study, and tissue analyses are currently ongoing) - Direct injection of BB-301
into the tibialis anterior muscle of A17 mice achieved robust transduction of the targeted skeletal muscle cells - This follow-up study in Beagle dogs is being conducted to optimize the proprietary dosing and surgical administration procedures
for BB-301 injection into the pharyngeal muscle tissues that underlie the morbidity and mortality of OPMD and to refine the core analytical methods employed following the completion of dosing 12-week GLP Toxicology and Biodistribution study
in Beagle dogs Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 10 www.benitec.com
8-Week BB-301 Pilot Dosing Study in Beagle Dogs: Study Rationale and
Background BB-301 is directly injected into the pharyngeal muscles known to underlie the morbidity and mortality characterizing the natural history of OPMD, and large animals (e.g. canine subjects) possess anatomical architecture in the
pharyngeal region similar to that of Human subjects with OPMD and were, therefore, identified by global regulatory agencies and our key collaborators as ideal subjects for the IND-enabling studies Against this backdrop, the BB-301 Pilot
Dosing Study in Beagle dogs was conducted to demonstrate that direct intramuscular injection of BB-301 via the use of a proprietary dosing device in an open surgical procedure could safely achieve the following goals: - Biologically
significant, highly-consistent, dose-dependent levels of BB-301 tissue transduction (i.e. delivery of the multi-functional genetic construct into the target pharyngeal muscle cells) - Durable, broad-based, dose-dependent expression within the
pharyngeal muscle cells of the three distinct genes comprising the BB-301 gene construct (i.e. siRNA13, siRNA17, and codon optimized PABPN1) - Durable and biologically significant levels of target gene knock-down (i.e. inhibition of the
expression of the gene of interest) within the pharyngeal muscle cells Copyright Benitec Biopharma Inc Copyright Benitec Biopharma Ltd 11 www.benitec.com8-Week BB-301 Pilot Dosing Study in Beagle Dogs: Study Rationale and Background