Benitec Biopharma Inc. · NASDAQ:BNTC
Benitec Biopharma — Investor Presentation (March 2025)
41 slides from Benitec Biopharma's investor presentation, March 2025
Slide 1: Corporate Presentation March 2025
C O R P O R AT E P R E S E N TAT I O N MARCH 2025 1
Slide 2: Safe Harbor Statement
Safe Harbor Statement Except for the historical information set forth herein, the matters set forth in this presentation include forward-looking statements, including statements regarding Benitec’s plans to develop and commercialize its product candidates, the timing of the completion of pre-clinica
Slide 3: Company Highlights
Company Highlights • DNA-directed RNA interference (ddRNAi) “Silence and Replace” platform combines gene therapy with RNA interference Novel ddRNAi “Silence to simultaneously silence and replace disease-causing genes permanently following a single administration and Replace” Platform • The ddRNAi pl
Slide 4: Interim Clinical Study Findings (October 2024, World Muscle Society)
Interim Clinical Study Findings (October 2024, World Muscle Society) • Five Subjects have been safely treated with BB-301 (1.2e13 vg/Subject), and no Serious Adverse Events were noted • Interim clinical results for the first 2 Subjects were disclosed in October 2024, 9-months and 6-months following
Slide 5: Oculopharyngeal Muscular Dystrophy: Clinical and Pathophysiological Overview
Oculopharyngeal Muscular Dystrophy: Clinical and Pathophysiological Overview 5
Slide 6: OPMD: A Debilitating, Progressive Disease With No Approved Therapies
OPMD: A Debilitating, Progressive Disease With No Approved Therapies • Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, chronic, myopathic disorder with a typical age of onset in the 40s-50s • OPMD results from a trinucleotide repeat expansion within exon 1 of the polyadenylate bi
Slide 7: Models for OPMD Pathogenesis
Models for OPMD Pathogenesis • PABPN1 is a ubiquitous protein that controls the length of mRNA poly(A) tails, mRNA export from the nucleus and alternative poly(A) site usage • Currently two general models are used to explain how alanine-expanded PABPN1 confers muscle pathology in autosomal dominant
Slide 8: OPMD: Overview of the Clinical Presentation
OPMD: Overview of the Clinical Presentation • OPMD typically presents with: • Ptosis (eyelid drooping) which can be asymmetric at onset • Difficulty swallowing (dysphagia) and choking during meals • A retrospective chart review was conducted at the Saguenay Neuromuscular Clinic (Quebec, Canada) to s
Slide 9: Current Clinical Management Strategies for Dysphagia in OPMD Patients Do Not Prevent Disease Progression
Current Clinical Management Strategies for Dysphagia in OPMD Patients Do Not Prevent Disease Progression • Nutritional recommendations including dietary texture/consistency modifications • Surgical interventions for moderate to severe dysphagia have temporary effects and may require repeated adminis
Slide 10: BB-301 Inhibits the Production of the Key Disease-Causing Protein in OPMD
BB-301 Inhibits the Production of the Key Disease-Causing Protein in OPMD and Delivers a New, Fully-Functional Version of the Protein • BB-301 is a gene therapy designed to accomplish two goals: Design of Lead Candidate * BB-301 • Reduce the production of the mutant form of the PABPN1 protein in the
Slide 11: ddRNAi Silence and Replace Platform Enables Permanent Silencing AND Replacement
ddRNAi “Silence and Replace” Platform Enables Both Permanent Silencing AND Replacement of Mutated Genes in the Target Tissue LIMITATIONS OF CURRENT siRNA TECHNOLOGIES: • Requires repeated administration • Enables only transient silencing of mutated gene • Silencing capacity restricted to a single ge
Slide 12: BB-301 Facilitated Robust Molecular Activity and Restoration of Muscle Strength in A17 Mouse Model
BB-301 Administration Facilitated Robust Molecular Activity and Complete Restoration of Muscle Strength in the OPMD A17 Mouse Model • Improvements in muscle strength in A17 mice were observed at the lowest gene replacement level • The lowest effective dose tested in A17 mice is currently being evalu
Slide 13: Pathophysiology of Dysphagia in OPMD
Pathophysiology of Dysphagia in OPMD 13
Slide 14: Impaired Clearance of Food and Liquid Can Lead to Aspiration, Aspiration Pneumonia, and Death
Impaired Clearance of Food and Liquid Can Lead to Aspiration, Aspiration Pneumonia, and Death Approximately one third of subjects had respiratory diagnoses listed as the cause of death: • Impaired swallowing (dysphagia) can lead to aspiration pneumonia • Pneumonia can result from the aspiration of f
Slide 15: Distinct Drivers of Dysphagia: Inefficient Swallowing and Ineffective Swallowing
Distinct Drivers of Dysphagia Observed in the OPMD Study Population: Inefficient Swallowing and Ineffective Swallowing • OPMD Subjects enrolled into the OPMD Natural History Study and the BB-301 Phase 1b/2a Clinical Study can be impacted by the post swallow accumulation of food and liquid or “ineffi
Slide 16: Swallowing Overview and the Rationale for BB-301 in OPMD
Swallowing Overview and the Rationale for BB-301 in OPMD OPMD Drives Disordered Swallowing Anatomical Structures of the Pharynx and BB-301 Injection Sites • In OPMD, the pharyngeal constrictor muscles are weakened and atrophic and unable to support the propulsion of food or liquid towards the esopha
Slide 17: BB-301 Clinical Development Program
BB-301 Clinical Development Program 17
Slide 18: BB-301 Clinical Development Program (Estimated Timeline for Cohort 1)
BB-301 Clinical Development Program (Estimated Timeline for Cohort 1) Subject (2024) (2024) (2024) (2025) (2025) (2025) (2025) October November December January February March April 1 (Treated 4Q2023) 2 (Treated 1Q2024) 3 Treated 4 Treated 5 Treated 6 Projected Dosing • First Subject entered Cohort
Slide 19: BB-301 Clinical Development Program
BB-301 Clinical Development Program OPMD Natural BB-301 Phase 1b/2a Open-Label History Study Dosing Dose Escalation Study (26wk) (1 Day) (NCT06185673) (52wk)* 23 Subjects Natural History Study Study can enroll enrolled as of Subjects enroll into the up to 30 Subjects Jan 2024 Phase 1b/2a Study Clini
Slide 20: Key Assessments: Subject-Reported and Videofluoroscopic Endpoints
Key Assessments: Subject-Reported and Videofluoroscopic Endpoints The key secondary endpoints of the OPMD Natural History Study and the BB-301 Phase 1b/2a Clinical Study (NCT06185673) facilitate serial characterization of: • Subject-Reported Oral-Pharyngeal Dysphagia (via use of the 17-question pati
Slide 21: Subject-Reported Oral-Pharyngeal Dysphagia: Sydney Swallow Questionnaire (SSQ) Scoring
Subject-Reported Oral-Pharyngeal Dysphagia: Sydney Swallow Questionnaire (SSQ) Scoring SSQ Example Questions Subject-reported oral-pharyngeal dysphagia as assessed by the SSQ: • The SSQ is a 17-item self-report inventory assessing subjective symptoms of oral-pharyngeal dysphagia • The questionnaire
Slide 22: Swallowing Inefficiency: As Measured by Post Swallow Total Pharyngeal Residue
Swallowing Inefficiency: As Measured by Post Swallow Total Pharyngeal Residue • C2-C4 length serves as an anatomical scalar • Total Pharyngeal Residue measurement comprises the amount of food or liquid material remaining in the pharynx after the first swallow of the bolus • Measurement (yellow, gree
Slide 23: Swallowing Ineffectiveness: As Measured by the Frequency of Pathologic Sequential Swallows
Swallowing Ineffectiveness: As Measured by the Frequency of Pathologic Sequential Swallows • Sequential swallowing is defined as the completion of two or more consecutive swallows in rapid succession where the hyolaryngeal complex (HLC) does not return to rest and the pharynx lacks complete patency
Slide 24: Interim Cohort 1 Phase 1b Clinical Data Demonstrate Clinically Meaningful Improvements
Interim Cohort 1 Phase 1b Clinical Data Demonstrate Clinically Meaningful Improvements in Swallowing Function for the Two Discrete Causes of Dysphagia 24
Slide 25: Pre-Treatment Characteristics Demonstrate Distinct Drivers of Dysphagia
Pre-Treatment Characteristics Demonstrate Distinct Drivers of Dysphagia • The total symptom burden was significant for both Subjects based on the Total SSQ Scores • Inefficient Swallowing (accumulation of food/liquid residue post-swallow) Drives Dysphagia for Subject 1 • Ineffective Swallowing (path
Slide 26: 9-Months Post BB-301: VFSS TPR Reductions in Post Swallow Residue for Subject 1
9-Months Post BB-301 Treatment: VFSS TPR Assessments Demonstrate Significant, Clinically Meaningful Reductions in Post Swallow Residue Across all Consistencies for Subject 1 24 Thin Liquid TPR Thick Liquid1 TPR 24 TPR TPR 15.1 30% improvement vs. 18 18 Pre-dose Average TPR TPR(%) 33% improvement vs.
Slide 27: 9-Months Post BB-301: Total SSQ Score Reductions for Subject 1
9-Months Post BB-301 Treatment: Total SSQ Scores Demonstrate Significant, Clinically Meaningful Reductions in the Dysphagic Deficits Experienced by Subject 1 • The 9-Month Average Post-Dose SSQ Score Demonstrated a 35% Improvement vs. the Average Pre-Dose SSQ Score Sydney Swallow Questionnaire Total
Slide 28: 6-Months Post BB-301: VFSS TPR Stabilization for Subject 2
6-Months Post BB-301 Treatment: VFSS TPR Assessments Demonstrate Stabilization in Post Swallow Residue for Thin Liquid and Solid Food for Subject 2 24 Thick Liquid1 TPR 24 Thin Liquid TPR TPR TPR 18 18 5.6-point increase vs. Pre-dose Average TPR TPR(%) TPR(%) 12 12 8.2 Stabilization of TPR 6 2.6 6 1
Slide 29: 6-Months Post BB-301: Reductions in Pathologic Sequential Swallows for Subject 2
6-Months Post BB-301 Treatment: VFSS Assessments Demonstrate Significant, Clinically Meaningful Reductions in the Frequency of Pathologic Sequential Swallows for Subject 2 For Subject 2, pathologic sequential swallows for thin liquid were observed: VFSS Thin Liquid Tasks Demonstrating Pathologic Seq
Slide 30: 6-Months Post BB-301: Total SSQ Score Reductions for Subject 2
6-Months Post BB-301 Treatment: Total SSQ Scores Demonstrate Significant, Clinically Meaningful Reductions in the Dysphagic Deficits Experienced by Subject 2, with Subject 2 Achieving Scores Representing Clinically Normal Swallowing • The 6-Month Average Post-Dose SSQ Score Showed an 89% Improvement
Slide 31: Summary and Conclusions
Summary and Conclusions • Two Subjects with distinct dysphagic profiles were safely treated with BB-301 (1.2e13 vg/Subject) and experienced significant, clinically meaningful improvements in swallowing function • There were no Severe Adverse Events • Both Subjects experienced significant reductions
Slide 32: Broad Intellectual Property Portfolio
Broad Intellectual Property Portfolio • OPMD Family 5 OPMD-related • OPMD Family 4 intellectual property • OPMD Family 2 • OPMD Family 1 AAV-related • AAV Family 1 intellectual property 32
Slide 33: Financial Summary
Financial Summary Nasdaq Listed: BNTC Shares Outstanding Cash & Cash Equivalents • Exclusively Nasdaq listed; re- • 23,451,475 as of 02/25/25 • $76mm as of 02/25/25 domiciled in April 2020 33
Slide 34: Appendix
Appendix 34
Slide 35: BB-301 Inhibits the Production of the Key Disease-Causing Protein in OPMD
BB-301 Inhibits the Production of the Key Disease-Causing Protein in OPMD and Delivers a New, Fully-Functional Version of the Protein • BB-301 is a gene therapy designed by Benitec Biopharma Inc. to accomplish two goals: Design of Lead Candidate * BB-301 • Reduce the production of the mutant (harmfu
Slide 36: IND-Enabling Studies for BB-301
IND-Enabling Studies for BB-301 Pilot Dosing Study in Beagle Dogs Toxicology Study in Beagle Dogs • 8-week study to confirm the transduction 12-week GLP Toxicology and Biodistribution efficiency of BB-301 following direct study in Beagle dogs intramuscular injection into the pharyngeal muscles via t
Slide 37: Dose-Dependent BB-301 Tissue Transduction in Beagle Dogs
Dose-Dependent BB-301 Tissue Transduction Observed 8 Weeks Following Direct Intramuscular Injection in Beagle Dogs Copies of BB-301 (average copies per cell) BB-301 Dose Hypopharyngeal Thyropharyngeal 5.66 (vg/mL) Muscle 5.12 Muscle 3.00 x 1013 vg/ml 5.12 5.66 High Volume 3.00 x 1013 vg/ml 3.15 2.70
Slide 38: Dose-Dependent Expression of coPABPN1 in Beagle Dogs
Dose-Dependent Expression of coPABPN1 Observed 8 Weeks Following Direct Intramuscular Injection of BB-301 in Beagle Dogs Copies of coPABPN1 (average copies per cell) BB-301 Dose Hypopharyngeal Thyropharyngeal 5.66 (vg/mL) Muscle 5.12 Muscle 3.00 x 1013 vg/ml 61.69 77.26 High Volume 3.00 x 1013 vg/ml
Slide 39: Dose-Dependent Expression of siRNA13, siRNA17 in Beagle Dogs
Dose-Dependent Expression of siRNA13, siRNA17 Observed 8 Weeks Following Direct Intramuscular Injection of BB-301 in Beagle Dogs siRNA13 siRNA17 Hypopharyngeal Thyropharyngeal Hypopharyngeal Thyropharyngeal Muscle Muscle Muscle Muscle BB-301 Dose average copies per 5.66 average copies per cell avera
Slide 40: Dose-Dependent Inhibition of PABPN1 in Beagle Dogs
Dose-Dependent Inhibition of PABPN1 Observed 8 Weeks Following Direct Intramuscular Injection of BB-301 in Beagle Dogs Average Reported % Inhibition of wtPABPN1 BB-301 Dose Hypopharyngeal Thyropharyngeal 5.66 (vg/mL) Muscle Muscle 5.12 3.00 x 1013 vg/ml 83% 82% High Volume 3.00 x 1013 vg/ml 74% 64%
Slide 41: Primary Source Data Verification
Primary Source Data Verification • All safety data are confirmed via a process of Source Data Verification (SDV) approximately monthly • The SDV process entails a clinical representative of the Clinical Research Organization (CRO) visiting the clinical site and reviewing all primary medical data ent
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