Benitec Biopharma Inc. · NASDAQ:BNTC
Benitec Biopharma — Technical Presentation (March 2025)
31 slides from Benitec Biopharma's technical presentation, Mar 19, 2025
Slide 1: Interim Study Update for BB-301 Gene Therapy Phase 1b/2a First in Human Trial in OPMD
Interim Study Update for BB-301 Gene Therapy Phase 1b/2a First in Human Trial in Subjects with Oculopharyngeal Muscular Dystrophy with Dysphagia Study Presenter: Jerel A. Banks, M.D., Ph.D. Chief Executive Officer and Chairman of the Board, Benitec Biopharma, Inc. March 19, 2025 Study Authors: Jerel
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: OPMD is a Debilitating Progressive Disease With No Approved Therapies
OPMD is a Debilitating Progressive Disease With No Approved Therapies • Oculopharyngeal Muscular Dystrophy (OPMD) is a rare (»15,000 patients in North America, Europe, and Israel), autosomal-dominant degenerative muscle disorder, caused by a mutation in the poly(A)-binding protein nuclear 1 (PABPN1)
Slide 4: BB-301 Clinical Development Program
BB-301 Clinical Development Program OPMD Natural BB-301 Phase 1b/2a Open-Label Dose History Study Dosing Escalation Study (NCT06185673) (26wk) (1 Day) (52wk)* 23 Subjects Natural History Study Study can enroll up to 30 Subjects enrolled as of Jan Subjects enroll into the As of February 2025, 5 Subje
Slide 5: 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 6: Clinical Utility, Sensitivity, and Specificity of Key Assessment Methods
Clinical Utility, Sensitivity, and Specificity of Key Assessment Methods • In the BB-301 Phase 1b/2a Clinical Treatment Study, Radiologists and Speech Language Pathologists employ serial VFSS to objectively characterize the nature and severity of anatomical and functional abnormalities present in ea
Slide 7: Distinct Drivers of Dysphagia Observed in the OPMD Study Population
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 Treatment Study can be impacted by the post swallow accumulation of food and liquid
Slide 8: Interim Cohort Phase 1b Clinical Data Demonstrate Clinically Meaningful Improvements in Swallowing Function
Interim Cohort 1 Phase 1b Clinical Data Demonstrate Clinically Meaningful Improvements in Swallowing Function for the Two Discrete Causes of Dysphagia 8
Slide 9: Pre-Treatment Characteristics Demonstrate Distinct Drivers of Dysphagia
Pre-Treatment Characteristics Demonstrate Distinct Drivers of Dysphagia • Inefficient Swallowing (accumulation of food/liquid residue post-swallow) Drives Dysphagia for Subject 1 • Ineffective Swallowing (pathologic sequential swallows or rapid involuntary contractions of the pharyngeal muscles betw
Slide 10: 12-Months Post BB-301: VFSS TPR Reductions for Subject 1
12-Months Post BB-301 Treatment : VFSS TPR Assessments Demonstrate Significant, Clinically Meaningful Reductions of Post Swallow Residue Across all Consistencies for Subject 1 Total Pharyngeal Residue 30 29% improvement vs. Pre-dose Average TPR 25 18% improvement vs. Pre-dose Average TPR 20 15.1 Tot
Slide 11: 12-Months Post BB-301: Total SSQ Score Reductions for Subject 1
12-Months Post BB-301 Treatment: Total SSQ Scores Demonstrate Significant, Clinically Meaningful Reductions in the Total Dysphagic Symptom Burden Experienced by Subject 1 • The 12-Month Average Post-Dose SSQ Score Showed a 41% Improvement vs. the Average Pre-Dose SSQ Score Sydney Swallow Questionnai
Slide 12: 12-Months Post BB-301: VFSS TPR Assessments for Subject 2
12-Months Post BB-301 Treatment: VFSS TPR Assessments Demonstrate Stabilization of Post Swallow Residue for Thin Liquid and Reduction of Post Swallow Residue for Solid Food for Subject 2 Total Pharyngeal Residue 30 25 20 Total Pharyngeal Residue (%) 6.5-point increase vs. Pre-dose Average TPR 11% im
Slide 13: 12-Months Post BB-301: Reduced Pathologic Sequential Swallows for Subject 2
12-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: • during 12 of the 15 swallowing tasks (frequency
Slide 14: 12-Months Post BB-301: Total SSQ Scores for Subject 2
12-Months Post BB-301 Treatment: Total SSQ Scores Demonstrate Significant, Clinically Meaningful Reductions in the Total Dysphagic Symptom Burden Experienced by Subject 2, with Subject 2 Achieving Scores Representing Clinically Normal Swallowing • The 12-Month Average Post-Dose SSQ Score Showed a 91
Slide 15: 3-Months Post BB-301: VFSS TPR Assessments for Subject 3
3-Months Post BB-301 Treatment: VFSS TPR Assessments Demonstrate Significant, Clinically Meaningful Reductions of Post Swallow Residue for Thick Liquid and Stabilization of Post Swallow Residue for Solid Food for Subject 3 Total Pharyngeal Residue 30 22.6 20% improvement vs. 25 Pre-dose Average TPR
Slide 16: 3-Months Post BB-301: Reduced Pathologic Sequential Swallows for Subject 3
3-Months Post BB-301 Treatment: VFSS Assessments Demonstrate Significant, Clinically Meaningful Reductions in the Frequency of Pathologic Sequential Swallows for Subject 3 For Subject 3, pathologic sequential swallows for Thin and Thick liquids were VFSS Thin Liquid Tasks and Thick Liquid Tasks obse
Slide 17: 3-Months Post BB-301: Total SSQ Scores for Subject 3
3-Months Post BB-301 Treatment: Total SSQ Scores Demonstrate Significant, Clinically Meaningful Reductions in the Total Dysphagic Symptom Burden Experienced by Subject 3, with Subject 3 Achieving Scores Representing Clinically Normal Swallowing • The 3-Month Post-Dose SSQ Score Showed a 68% Improvem
Slide 18: Summary and Conclusions
Summary and Conclusions • Three Subjects with distinct causes of their respective total dysphagic symptom burdens 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 • All thr
Slide 19: Acknowledgements
Acknowledgements Department of Otolaryngology-Head and Neck Surgery New York University Grossman School of Medicine Milan R. Amin, M.D., Principal Investigator Efstratios Achlatis, M.D. Matina Balou, Ph.D. The entire NYU Clinical team including nurses, pharmacists and administrative staff who have h
Slide 20: Appendix
Appendix 20
Slide 21: BB-301 Inhibits the Production of the Key Disease-Causing Protein in OPMD and Delivers a Functional Protein
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 22: 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 23: 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 24: 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 25: 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 26: 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 efficiency of • 12-week GLP Toxicology and Biodistribution BB-301 following direct intramuscular injection into study in Beagle dogs the pharyngeal muscles via
Slide 27: 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) 5.66 BB-301 Dose (vg/mL) Hypopharyngeal Muscle Thyropharyngeal Muscle 5.12 3.00 x 1013 vg/ml 5.12 5.66 High Volume 3.00 x 1013 vg/ml 3.15 2.70
Slide 28: 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) 5.66 BB-301 Dose (vg/mL) Hypopharyngeal Muscle Thyropharyngeal Muscle 5.12 3.00 x 1013 vg/ml 61.69 77.26 High Volume 3.00 x 1013 vg/ml
Slide 29: 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 Muscle Thyropharyngeal Muscle Hypopharyngeal Muscle Thyropharyngeal Muscle BB-301 Dose (vg/mL) average copies per cell average copies per ce
Slide 30: 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 (vg/mL) Hypopharyngeal Muscle Thyropharyngeal Muscle 5.66 5.12 3.00 x 1013 vg/ml 83% 82% High Volume 3.00 x 1013 vg/ml 74% 64%
Slide 31: 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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