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What changed in Benitec Biopharma Inc.'s 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of Benitec Biopharma Inc.'s 2023 and 2024 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2024 report.

+298 added−328 removedSource: 10-K (2024-09-26) vs 10-K (2023-09-21)

Top changes in Benitec Biopharma Inc.'s 2024 10-K

298 paragraphs added · 328 removed · 208 edited across 5 sections

Item 1. Business

Business — how the company describes what it does

65 edited+43 added−18 removed223 unchanged
Biggest changeCritically, each of the clinical and videofluoroscopic assessments employed in the FIH study will be equivalent to those employed for the NH study to facilitate comparative clinical and statistical analyses for each study subject. • The primary and secondary endpoints will be evaluated during each 90-day period following BB-301 intramuscular injection (Day 1). • The NH of dysphagia observed for each OPMD study participant, as characterized by the VFSS and clinical swallowing assessments carried out during the NH Study, will serve as the baseline for comparative assessments of safety and efficacy of BB-301 upon rollover from the NH Study onto the BB-301 Phase 1b/2a Treatment Study. • In December 2022, Benitec began screening OPMD subjects at the lead clinical study site in the United States. • In January 2023, Benitec announced the enrollment of the first OPMD subject into the NH Study in the United States. • As of September 2023, 15 subjects have been enrolled into the NH study in the United States. • The pace of enrollment of OPMD subjects into the NH Study at the U.S. clinical study site supports our central clinical development goals of: (1) administering BB-301 to OPMD subjects in 2H2023, and (2) disclosing the initial interim safety and efficacy data over the next 12 months for subjects that have received BB-301. 20 Table of Contents Additional Regulatory Updates for the Clinical Development Program: North America: • Formal submission of the comprehensive NH Study trial package to the Research Ethics Board (REB) for the lead clinical study site in Canada was completed, and Benitec awaits the formal response from the REB. • Approval of the NH Study trial package by the REB is required for clinical study site activation and OPMD patient screening and enrollment to begin in Canada.
Biggest changeCritically, each of the clinical and videofluoroscopic assessments employed in the FIH study will be equivalent to those employed for the NH study to facilitate comparative clinical and statistical analyses for each study subject. • The primary and secondary endpoints will be evaluated during each 90-day period following BB-301 intramuscular injection (Day 1). • The NH of dysphagia observed for each OPMD NH Study participant, as characterized by the VFSS and clinical swallowing assessments carried out during the NH Study, will serve as the baseline for comparative assessments of safety and efficacy of BB-301 upon rollover from the NH Study onto the BB-301 Phase 1b/2a Treatment Study (NCT06185673). • In December 2022, Benitec began screening OPMD subjects at the lead clinical study site in the United States. • In January 2023, Benitec announced the enrollment of the first OPMD subject into the NH Study in the United States. 19 Table of Contents • In November 2023, Benitec announced the completion of the administration of BB-301 to the first study subject in the Phase 1b/2a clinical study (NCT06185673) in the United States.
This fundamental therapeutic approach to disease management is called “silence and replace” and this biological mechanism offers the potential to restore the underlying physiology of the treated tissues and, in the process, improve treatment 7 Table of Contents outcomes for patients suffering from the chronic and, potentially, fatal effects of Oculopharyngeal Muscular Dystrophy (OPMD).
This fundamental therapeutic 7 Table of Contents approach to disease management is called “silence and replace” and this biological mechanism offers the potential to restore the underlying physiology of the treated tissues and, in the process, improve treatment outcomes for patients suffering from the chronic and, potentially, fatal effects of Oculopharyngeal Muscular Dystrophy (OPMD).
BB-301 has been granted Orphan Drug Designation in the United States and the European Union.
BB-301 has been granted Orphan Drug Designation in the United States and the European Union.
Furthermore, as part of this collaboration, we have generated a gene expression construct that produces a siRNA-resistant version of the wild type PABPN1 gene. In subsequent studies undertaken exclusively by Benitec, a second set of target regions within PABPN1 were identified for therapeutic development and shmiRs designed against these regions.
Furthermore, as part of this collaboration, we have generated a gene expression construct that produces a siRNA- resistant version of the wild type PABPN1 gene. In subsequent studies undertaken exclusively by Benitec, a second set of target regions within PABPN1 were identified for therapeutic development and shmiRs were designed against these regions.
The trademarks that we use in connection with our business include the following: Application or Country or Territory Trademark (program) Registration number Status USA BENITEC BIOPHARMA 86190065 Registered USA SILENCING GENES FOR LIFE 86488147 Registered Australia SILENCING GENES FOR LIFE 1448041 Registered Australia BENITEC BIOPHARMA 1448046 Registered Australia BENITEC—logo 1448052 Registered Australia Nervarna 1526478 Registered Australia TRIBETARNA 1526479 Registered Australia HEPBARNA 1526483 Registered International Bureau (WIPO) – designating EU; UK and US GIVING DISEASE THE SILENT TREATMENT 1389399 Registered USA BENITEC 86795296 Registered USA GIVING DISEASE THE SILENT TREATMENT 79226988 Registered European Union BENITEC 14680003 Registered Australia BENITEC 1728797 Registered Australia BENITEC 1103049 Registered Australia BENITEC 1103300 Registered Australia GIVING DISEASE THE SILENT TREATMENT 1851660 Registered United Kingdom BENITEC 3238275 Registered Manufacturing The manufacture of the biological products required for gene therapy is complex and difficult.
The trademarks that we use in connection with our business include the following: Application or Country or Territory Trademark (program) Registration number Status USA BENITEC BIOPHARMA 86190065 Registered USA SILENCING GENES FOR LIFE 86488147 Registered Australia SILENCING GENES FOR LIFE BENITEC 1448041 Registered Australia BIOPHARMA 1448046 Registered Australia BENITEC—logo 1448052 Registered Australia Nervarna 1526478 Registered Australia TRIBETARNA 1526479 Registered Australia HEPBARNA 1526483 Registered International Bureau (WIPO) – designating EU; UK and US GIVING DISEASE THE SILENT TREATMENT 1389399 Registered USA BENITEC 86795296 Registered USA GIVING DISEASE THE SILENT TREATMENT 79226988 Registered European Union BENITEC 14680003 Registered Australia BENITEC 1728797 Registered Australia BENITEC 1103049 Registered Australia BENITEC 1103300 Registered Australia GIVING DISEASE THE SILENT TREATMENT 1851660 Registered United Kingdom BENITEC 3238275 Registered Manufacturing The manufacture of the biological products required for gene therapy is complex and difficult.
Figure 8. siRNA13 Expression Levels for BB-301 within Pharyngeal Muscle Tissues Figure 9. siRNA17 Expression Levels for BB-301 within Pharyngeal Muscle Tissues 16 Table of Contents Figure 10. coPABPN1 Expression Levels for BB-301 within Pharyngeal Muscle Tissues Regarding Wild Type PABPN1 Silencing (i.e. target “knock-down”) Observed for BB-301 Within the Pharyngeal Muscle Tissues (Figure 11): • As noted above, BB-301 encodes two distinct siRNA species (i.e., siRNA13 and siRNA17) which are each, independently, capable of inhibiting (i.e., “silencing”) the expression of all forms of the PABPN1 protein (siRNA13 and siRNA17 silence the expression of both wild type PABPN1 [wtPABPN1] and mutant PABPN1). • While the Beagle dog subjects treated in the BB-301 Pilot Dosing Study did not express mutant PABPN1, the level of BB-301-driven gene silencing for the PABPN1 target can be accurately assessed due to the equivalent inhibitory effects of siRNA13 and siRNA17 on both wtPABPN1 and mutant PABPN1. • Thus, the wtPABPN1 silencing activity observed in the BB-301 Pilot Dosing Study served as a surrogate for the activity that would be anticipated in the presence of mutant PABPN1. • BB-301 has been evaluated in prior nonclinical studies in animals that express mutant PABPN1 and manifest the key signs and symptoms of OPMD and, in these animal models of OPMD, the achievement of PABPN1 silencing levels of 31% inhibition or higher led to resolution of OPMD disease symptoms and correction of the histological hallmarks of OPMD. 17 Table of Contents Figure 11.
Figure 8. siRNA13 Expression Levels for BB-301 within Pharyngeal Muscle Tissues and siRNA17 Expression Levels for BB-301 within Pharyngeal Muscle Tissues 16 Table of Contents Figure 9. coPABPN1 Expression Levels for BB-301 within Pharyngeal Muscle Tissues Regarding Wild Type PABPN1 Silencing (i.e. target “knock-down”) Observed for BB-301 Within the Pharyngeal Muscle Tissues (Figure 10): • As noted above, BB-301 encodes two distinct siRNA species (i.e., siRNA13 and siRNA17) which are each, independently, capable of inhibiting (i.e., “silencing”) the expression of all forms of the PABPN1 protein (siRNA13 and siRNA17 silence the expression of both wild type PABPN1 [wtPABPN1] and mutant PABPN1). • While the Beagle dog subjects treated in the BB-301 Pilot Dosing Study did not express mutant PABPN1, the level of BB-301-driven gene silencing for the PABPN1 target can be accurately assessed due to the equivalent inhibitory effects of siRNA13 and siRNA17 on both wtPABPN1 and mutant PABPN1. • Thus, the wtPABPN1 silencing activity observed in the BB-301 Pilot Dosing Study served as a surrogate for the activity that would be anticipated in the presence of mutant PABPN1. • BB-301 has been evaluated in prior nonclinical studies in animals that express mutant PABPN1 and manifest the key signs and symptoms of OPMD and, in these animal models of OPMD, the achievement of PABPN1 silencing levels of 31% inhibition or higher led to resolution of OPMD disease symptoms and correction of the histological hallmarks of OPMD.
Impact of Benitec-Initiated Methodological Improvements on the Relative Pharyngeal Muscle Tissue Transduction Levels Achieved for BB-301 Following the disclosure of the positive interim BB-301 Pilot Dosing Study results, Benitec completed pre-CTA and pre-IND meetings with regulatory agencies in France, Canada, and the United States. Summary of Regulatory Interactions: • In June 2023 the U.S.
Impact of Benitec-Initiated Methodological Improvements on the Relative Pharyngeal Muscle Tissue Transduction Levels Achieved for BB-301 Following the disclosure of the positive interim BB-301 Pilot Dosing Study results, Benitec completed pre-CTA and pre-IND meetings with regulatory agencies in France, Canada, and the United States. Summary of the Key Regulatory Interactions: • In June 2023 the U.S.
Operational Updates The key milestones related to the development of BB-301 for the treatment of OPMD, along with other corporate updates, are outlined below: BB-301 Clinical Development Program Overview: • The BB-301 clinical development program will be conducted in the United States and Canada, and the primary elements of the program are summarized below: • The program will comprise approximately 76 weeks of follow-up which we anticipate will consist of: • The OPMD Natural History (NH) Study: 6-month pre-treatment observation periods for the evaluation of baseline disposition and natural history of OPMD-derived dysphagia (swallowing impairment) in each study participant. • Dosing with BB-301: 1-day of BB-301 dosing to initiate participation in the Phase 1b/2a single-arm, open-label, sequential, dose-escalation cohort study.
Operational Updates The key milestones related to the development of BB-301 for the treatment of OPMD, along with other corporate updates, are outlined below: BB-301 Clinical Development Program Overview: • The BB-301 clinical development program will be conducted in the United States, and the primary elements of the program are summarized below: • The program will comprise approximately 76 weeks of follow-up which we anticipate will consist of: • The OPMD Natural History (NH) Study: 6-month pre-treatment observation periods for the evaluation of baseline disposition and natural history of OPMD-derived dysphagia (swallowing impairment) in each study participant. • Dosing with BB-301: 1-day of BB-301 dosing to initiate participation in the Phase 1b/2a single-arm, open-label, sequential, dose-escalation cohort study (NCT06185673).
We may encounter difficulties or unanticipated costs in our efforts to secure necessary governmental approvals, which could delay or preclude us from marketing our products. 29 Table of Contents Orphan Drug Designation Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biological product candidate intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making a drug or biological product available in the United States for this type of disease or condition will be recovered from sales of the product candidate.
We may encounter difficulties or unanticipated costs in our efforts to secure necessary governmental approvals, which could delay or preclude us from marketing our products. 30 Table of Contents Orphan Drug Designation Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biological product candidate intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making a drug or biological product available in the United States for this type of disease or condition will be recovered from sales of the product candidate.
In the future, if and when our products receive FDA approval, or approval from an equivalent regulatory body in another jurisdiction in which patent protection is sought or obtained, we expect to apply for patent term extensions on patents covering those products. 22 Table of Contents Trademarks Our trademarks include registrations for company branding and product names for our pipeline in development.
In the future, if and when our products receive FDA approval, and/or approval from an equivalent regulatory body in another jurisdiction in which patent protection is sought or obtained, we expect to apply for patent term extensions on patents covering those products. 23 Table of Contents Trademarks Our trademarks include registrations for company branding and product names for our pipeline in development.
Dose-Dependent Increases in Muscle Force Restoration of muscle strength was assessed by muscle contractility measurements in response to a series of induced impulses that ranged from 10 to 180 Hz Ongoing Development Activities for BB-301 On July 8, 2020, Benitec announced the initiation of the BB-301 Pilot Dosing Study in large animal subjects.
Dose-Dependent Increases in Muscle Force Restoration of muscle strength was assessed by muscle contractility measurements in response to a series of induced impulses that ranged from 10 to 180 Hz Subsequent Development Activities for BB-301 On July 8, 2020, Benitec announced the initiation of the BB-301 Pilot Dosing Study in large animal subjects.
They are performed after preliminary evidence suggesting effectiveness of the investigational product has been obtained, and are intended to further evaluate dosage, clinical effectiveness and safety, to establish the overall benefit-risk relationship of the product, and to provide an adequate basis for product approval. Phase III clinical trials usually involve several 27 Table of Contents hundred to several thousand participants.
They are performed after preliminary evidence suggesting effectiveness of the investigational product has been obtained, and are intended to further evaluate 28 Table of Contents dosage, clinical effectiveness and safety, to establish the overall benefit-risk relationship of the product, and to provide an adequate basis for product approval. Phase III clinical trials usually involve several hundred to several thousand participants.
Benitec conducted the BB-301 Pilot Dosing Study in Beagle dog subjects 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 and dose-dependent levels of BB-301 tissue transduction (i.e., delivery of the multi-functional BB-301 genetic construct into the target pharyngeal muscle cells); 14 Table of Contents • Broad-based and dose-dependent expression of the three distinct genes comprising the BB-301 gene construct within the pharyngeal muscle cells; and • 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.
Benitec conducted the BB-301 Pilot Dosing Study in Beagle dog subjects 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 and dose-dependent levels of BB-301 tissue transduction (i.e., delivery of the multi-functional BB-301 genetic construct into the target pharyngeal muscle cells); • Broad-based and dose-dependent expression of the three distinct genes comprising the BB-301 gene construct within the pharyngeal muscle cells; and • 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.
Pharyngeal Muscle Tissue Transduction Levels for BB-301 Regarding Gene Expression Levels Observed for BB-301 Within the Pharyngeal Muscle Tissues (Figure 8, Figure 9, Figure 10): • BB-301 encodes two distinct siRNA species (i.e., siRNA13 and siRNA17) which are each, independently, capable of inhibiting (i.e., “silencing”) the expression of the mutant form of the PABPN1 protein and the wild type (i.e., endogenous) form of the PABPN1 protein (importantly, the mutant form of the PABPN1 protein underlies the development and progression of OPMD). • BB-301 also codes for a wild type version of the PABPN1 protein whose intracellular expression is unaffected by the inhibitory activities of siRNA13 and siRNA17, and this codon optimized PABPN1 15 Table of Contents protein (i.e., coPABPN1) serves to replenish the endogenous form of the PABPN1 protein and to replace the mutant form of PABPN1 that underlies the development and progression of OPMD in diseased tissues. • For comparative purposes, it should be noted that the average range of expression for wild type PABPN1 within the pharyngeal muscle cells of Beagle dogs is 4.5 copies per cell-to-7.8 copies per cell.
Pharyngeal Muscle Tissue Transduction Levels for BB-301 Regarding Gene Expression Levels Observed for BB-301 Within the Pharyngeal Muscle Tissues (Figure 8, Figure 9): • BB-301 encodes two distinct siRNA species (i.e., siRNA13 and siRNA17) which are each, independently, capable of inhibiting (i.e., “silencing”) the expression of the mutant form of the PABPN1 protein and the wild type (i.e., endogenous) form of the PABPN1 protein (importantly, the mutant form of the PABPN1 protein underlies the development and progression of OPMD). • BB-301 also codes for a wild type version of the PABPN1 protein whose intracellular expression is unaffected by the inhibitory activities of siRNA13 and siRNA17, and this codon optimized PABPN1 protein (i.e., coPABPN1) serves to replenish the endogenous form of the PABPN1 protein and to replace the mutant form of PABPN1 that underlies the development and progression of OPMD in diseased tissues. • For comparative purposes, it should be noted that the average range of expression for wild type PABPN1 within the pharyngeal muscle cells of Beagle dogs is 4.5 copies per cell-to-7.8 copies per cell.
Dose-Dependent shRNA Expression 12 Table of Contents Figure 6b. Dose-Dependent PABPN1 Inhibition and Transgene Expression Figure 6c. Dose-Dependent Decreases in Intranuclear Inclusions 13 Table of Contents Figure 6d.
Dose-Dependent shRNA Expression Figure 6b. Dose-Dependent PABPN1 Inhibition and Transgene Expression 13 Table of Contents Figure 6c. Dose-Dependent Decreases in Intranuclear Inclusions Figure 6d.
The VFSS outlined below collectively provide objective assessments of global swallowing function and the function of the pharyngeal constrictor muscles (i.e., the muscles whose functional deterioration drives disease progression in OPMD): • Total Pharyngeal Residue %(C2-4) 2 • Pharyngeal Area at Maximum Constriction (PhAMPC) • Dynamic Imaging Grade of Swallowing Toxicity Scale (DIGEST) • Vallecular Residue %(C2-4) 2 , Pyriform Sinus Residue %(C2-4) 2, and Other Pharyngeal Residue %(C2-4) 2 • Normalized Residue Ratio Scale (NRRS v , NRRS p ) • Pharyngeal Construction Ratio (PCR) • The NH study will also employ clinical measures of global swallowing capacity and oropharyngeal dysphagia, along with two distinct patient-reported outcome instruments targeting the assessment of oropharyngeal dysphagia. • Upon the achievement of 6-months of follow-up in the NH Study, participants will, potentially, be eligible for enrollment into the BB-301 Phase 1b/2a treatment study. • BB-301 Phase 1b/2a Treatment Study: • This first-in-human (FIH) study will evaluate the safety and clinical activity of intramuscular doses of BB-301 administered to subjects with OPMD. • The primary endpoint of the FIH study will be safety. • Secondary endpoints are designed to determine the impact of BB-301 on swallowing efficiency, swallowing safety, and pharyngeal constrictor muscle function in subjects diagnosed with OPMD with dysphagia via the use of serial clinical and videofluoroscopic assessments.
The VFSS outlined below collectively provide objective assessments of global swallowing function and the function of the pharyngeal constrictor muscles (i.e., the muscles whose functional deterioration drives disease progression in OPMD): • Total Pharyngeal Residue %(C2-4) 2 • Pharyngeal Area at Maximum Constriction (PhAMPC) • Dynamic Imaging Grade of Swallowing Toxicity Scale (DIGEST) • Vallecular Residue %(C2-4) 2 , Pyriform Sinus Residue %(C2-4) 2 , and Other Pharyngeal Residue %(C2-4) 2 • Normalized Residue Ratio Scale (NRRSv, NRRSp) • Pharyngeal Construction Ratio (PCR) • The NH study will also employ clinical measures of global swallowing capacity and oropharyngeal dysphagia, along with two distinct patient-reported outcome instruments targeting the assessment of oropharyngeal dysphagia. • Upon the achievement of 6-months of follow-up in the NH Study, participants will, potentially, be eligible for enrollment into the BB-301 Phase 1b/2a treatment study (NCT06185673). • BB-301 Phase 1b/2a Treatment Study (NCT06185673): • This first-in-human (FIH) study will evaluate the safety and clinical activity of intramuscular doses of BB-301 administered to subjects with OPMD. • The primary endpoint of the FIH study will be safety. • Secondary endpoints are designed to determine the impact of BB-301 on swallowing efficiency, swallowing safety, and pharyngeal constrictor muscle function in subjects diagnosed with OPMD with dysphagia via the use of serial clinical and videofluoroscopic assessments.
If we receive marketing and commercialization approval for any of our 23 Table of Contents product candidates, we intend to market the product through strategic alliances and distribution agreements with third parties. In certain cases, we may market an approved product directly worldwide or in selected geographical segments.
If we receive marketing and commercialization approval for any of our product candidates, we intend to market the product through strategic alliances and distribution agreements with 24 Table of Contents third parties. In certain cases, we may market an approved product directly worldwide or in selected geographical segments.
All share and earnings per share amounts presented in this Form 10-K reflect the impact of this reverse split. Available Information Our telephone number is (510) 780-0819, and our Internet website is www.benitec.com.
All share and earnings per share amounts presented in this Form 10-Q reflect the impact of this reverse split. Available Information Our telephone number is (510) 780-0819, and our Internet website is www.benitec.com.
The targeted gene silencing effects of RNAi, in conjunction with the durable transgene expression achievable via the use of modified viral vectors, imbues the silence and replace approach with the potential to produce permanent silencing of disease-causing genes along with simultaneous replacement of the wild type gene function following a single administration of the proprietary genetic medicine.
The targeted gene silencing effects of RNAi, in conjunction with the durable transgene expression achievable via the use of modified viral vectors, imbues the silence and replace approach with the potential to produce permanent silencing of disease-causing genes along with simultaneous replacement of the wild type gene 3 Table of Contents function following a single administration of the proprietary genetic medicine.
The BB-301 Pilot Dosing Study was carried out under the guidance of the scientific team at Benitec, with key elements of the study design and execution conducted in close collaboration with a team of leading experts in both medicine and surgery that have been deeply engaged in the treatment of OPMD patients for several decades.
The BB-301 Pilot Dosing Study was carried out under the guidance of 14 Table of Contents the scientific team at Benitec, with key elements of the study design and execution conducted in close collaboration with a team of leading experts in both medicine and surgery that have been deeply engaged in the treatment of OPMD patients for several decades.
FDA Post-Approval Requirements Any products manufactured or distributed by us or on our behalf pursuant to FDA approvals are subject to continuing regulation by the FDA, including requirements for record-keeping, reporting of adverse experiences 31 Table of Contents with the biologic or drug, and submitting biological product deviation reports to notify the FDA of unanticipated changes in distributed products.
FDA Post-Approval Requirements Any products manufactured or distributed by us or on our behalf pursuant to FDA approvals are subject to continuing regulation by the FDA, including requirements for record-keeping, reporting of adverse experiences with the biologic or drug, and submitting biological product deviation reports to notify the FDA of unanticipated changes in distributed products.
Modified AAV vectors are employed to deliver genetic constructs which encode short hairpin RNAs that are, then, serially expressed and processed to produce siRNA molecules within the transduced cell for the duration of the life of the target cell. These newly introduced siRNA molecules drive 3 Table of Contents permanent silencing of the expression of the disease-causing gene.
Modified AAV vectors are employed to deliver genetic constructs which encode short hairpin RNAs that are, then, serially expressed and processed to produce siRNA molecules within the transduced cell for the duration of the life of the target cell. These newly introduced siRNA molecules drive permanent silencing of the expression of the disease-causing gene.
BB-301 will be delivered directly to the pharyngeal muscles of each study subject. • Phase 1b/2a Treatment Evaluation: 52-weeks of post-dosing follow-up for conclusive evaluation of the primary and secondary endpoints of the BB-301 Phase 1b/2a treatment study, with interim safety and efficacy results expected to be available at the end of each 90-day period following the administration of BB-301. 19 Table of Contents • The OPMD NH Study will characterize the level of dysphagia borne by each OPMD subject at baseline and assess subsequent progression of dysphagia via the use of the following quantitative radiographic measures (i.e., videofluoroscopic swallowing studies or “VFSS”).
BB-301 will be delivered directly to the pharyngeal muscles of each study subject. 18 Table of Contents • Phase 1b/2a Treatment Evaluation: 52-weeks of post-dosing follow-up for conclusive evaluation of the primary and secondary endpoints of the BB-301 Phase 1b/2a treatment study (NCT06185673), with interim safety and efficacy results expected to be available at the end of each 180-day period following the administration of BB-301. • The OPMD NH Study will characterize the level of dysphagia borne by each OPMD subject at baseline and assess subsequent progression of dysphagia via the use of the following quantitative radiographic measures (i.e., videofluoroscopic swallowing studies or “VFSS”).
To obtain regulatory approval of a biological product under European Union regulatory systems, we must submit a marketing authorization application. The application required in the European Union is similar to a BLA in the 33 Table of Contents United States, with the exception of, among other things, country-specific document requirements. The European Union also provides opportunities for market exclusivity.
To obtain regulatory approval of a biological product under European Union regulatory systems, we must submit a marketing authorization application. The application required in the European Union is similar to a BLA in the United States, with the exception of, among other things, country-specific document requirements. The European Union also provides opportunities for market exclusivity.
Manufacturers are required to register their facilities with the FDA and certain state agencies, and are subject to periodic announced or unannounced inspections by the FDA and certain state agencies for compliance with cGMP requirements, which impose certain quality processes, manufacturing controls and documentation requirements upon us and our third-party manufacturers in order to ensure that the product is safe, has the identity and strength, and meets the quality, purity and potency characteristics that it purports to have.
Manufacturers are required to register their facilities with the FDA and certain 32 Table of Contents state agencies, and are subject to periodic announced or unannounced inspections by the FDA and certain state agencies for compliance with cGMP requirements, which impose certain quality processes, manufacturing controls and documentation requirements upon us and our third- party manufacturers in order to ensure that the product is safe, has the identity and strength, and meets the quality, purity and potency characteristics that it purports to have.
In addition, the FDA 30 Table of Contents currently requires as a condition for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.
In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional materials, which could 31 Table of Contents adversely impact the timing of the commercial launch of the product.
The Hatch-Waxman Amendments permit a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process. However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.
The 33 Table of Contents Hatch-Waxman Amendments permit a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process. However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.
For example, in the European Union, upon receiving marketing authorization, a new biological generally receives eight years of data exclusivity and an additional two years of market exclusivity. If granted, data exclusivity prevents regulatory authorities in the European Union from referencing the innovator’s data to assess a biosimilar application.
For example, in the European Union, upon receiving marketing authorization, a new biological generally receives eight years of data exclusivity and an additional two 34 Table of Contents years of market exclusivity. If granted, data exclusivity prevents regulatory authorities in the European Union from referencing the innovator’s data to assess a biosimilar application.
BB-301 dosing was carried out independently by both a veterinary surgeon and a practicing Otolaryngologist who has extensive experience with the provision of palliative surgical care for OPMD patients. The key results are summarized here: Figure 7.
BB-301 dosing was carried out independently by both a veterinary surgeon and a practicing Otolaryngologist who has extensive experience with the provision of palliative surgical care for OPMD patients. 15 Table of Contents The key results are summarized here: Figure 7.
The second patent family, entitled “Reagents for treatment of oculopharyngeal muscular dystrophy (OPMD) and use thereof (OPMD family #2)” relates to a second set of target gene sequences within PABPN1 as well as ‘silence and replace’ construct BB-301 under development at Benitec.
The second patent family, entitled “Reagents for treatment of oculopharyngeal muscular dystrophy (OPMD) and use thereof (OPMD family #2)” relates to a second set of target regions within PABPN1, as well as the ‘silence and replace’ construct BB-301 under development at Benitec.
The eligibility of the RMAT-designated product for these expedited 25 Table of Contents programs can be discussed with the FDA at specific development meetings, but we do not know whether any of our current or future product candidates will be eligible for RMAT designation.
The eligibility of the RMAT-designated product for these expedited programs can be discussed with the FDA at specific development meetings, but we do not know whether any of our current or future product candidates will be eligible for RMAT designation.
In the A17 mouse model, the treatment restores muscle strength and muscle weight to wild type levels and improves other physiological hallmarks of the disease (Figure 6a, Figure 6b, Figure 6c, Figure 6d): • Multiple A17 animal cohorts received single doses of BB-301 (over a range of doses spanning 4x10 8 vg/muscle-to-7.5x10 11 vg/muscle) and, following BB-301 administration, each cohort was observed for 14-weeks • BB-301 was injected into the Tibialis Anterior (TA) muscle of 10 week old-to-12 week old animals and, 14-weeks post administration, each A17 cohort was anesthetized and the contractile properties of the injected TA muscles were analyzed via in-situ muscle electrophysiology • Intermediate doses of BB-301 resulted in 75% silencing of PABPN1 and 26% replacement of wild type PABPN1 activity, leading to full restoration of muscle strength, clearance of INIs, and a reduction of fibrosis • An additional experiment conducted over the course of 20-weeks demonstrated that more modest doses of BB-301 (which supported only partial resolution of the disease phenotype at week-14) were, surprisingly, able to facilitate significant benefit at 20-weeks, as evidenced by restoration of parameters relating to muscle strength, weight and INI formation Figure 6a.
In the A17 mouse model, the treatment restores muscle strength and muscle weight to wild type levels and improves other physiological hallmarks of the disease (Figure 6a, Figure 6b, Figure 6c, Figure 6d): • Multiple A17 animal cohorts received single doses of BB-301 (over a range of doses spanning 4x108 vg/muscle-to-7.5x1011 vg/muscle) and, following BB-301 administration, each cohort was observed for 14-weeks • BB-301 was injected into the Tibialis Anterior (TA) muscle of 10 week old-to-12 week old animals and, 14-weeks post administration, each A17 cohort was anesthetized and the contractile properties of the injected TA muscles were analyzed via in-situ muscle electrophysiology • Intermediate doses of BB-301 resulted in 75% silencing of PABPN1 and 26% replacement of wild type PABPN1 activity, leading to full restoration of muscle strength, clearance of INIs, and a reduction of fibrosis • An additional experiment conducted over the course of 20-weeks demonstrated that more modest doses of BB-301 (which supported only partial resolution of the disease phenotype at week-14) were, surprisingly, able to facilitate significant benefit at 20-weeks, as evidenced by restoration of parameters relating to muscle strength 12 Table of Contents Figure 6a.
Food and Drug Administration (FDA) cleared the Investigational New Drug (IND) application for BB-301 which allows dosing of BB-301 to begin for OPMD subjects that are eligible for enrollment into the Phase 1b/2a treatment study (described below).
Food and Drug Administration (FDA) cleared the Investigational New Drug (IND) application for BB-301 which allowed dosing of BB-301 to begin for OPMD subjects that are eligible for enrollment into the Phase 1b/2a treatment study (NCT06185673) described below.
The steps required before a new biologic may be marketed in the United States generally include: • nonclinical pharmacology and toxicology laboratory and animal tests according to good laboratory practices, or GLPs, and applicable requirements for the humane use of laboratory animals or other applicable regulations; • submission of an IND application which must become effective before human clinical trials may begin; • adequate and well-controlled human clinical trials according to GCPs and any additional requirements for the protection of human research subjects and their health information to establish the safety and efficacy of the investigational product for each targeted indication; • submission of a biologics license application, or BLA, to the FDA; • FDA’s pre-approval inspection of manufacturing facilities to assess compliance with cGMPs and, if applicable, the FDA’s good tissue practices, or GTPs, for the use of human cellular and tissue products to prevent the introduction, transmission, or spread of communicable diseases; • FDA’s audit of clinical trial sites that generated data in support of the BLA; and • FDA approval of a BLA, which must occur before a product can be marketed or sold.
The steps required before a new biologic may be marketed in the United States generally include: • nonclinical pharmacology and toxicology laboratory and animal tests according to good laboratory practices, or GLPs, and applicable requirements for the humane use of laboratory animals or other applicable regulations; • submission of an IND application which must become effective before human clinical trials may begin; • adequate and well-controlled human clinical trials according to GCPs and any additional requirements for the protection of human research subjects and their health information to establish the safety and efficacy of the investigational product for each targeted indication; • submission of a biologics license application, or BLA, to the FDA; • FDA’s pre-approval inspection of manufacturing facilities to assess compliance with cGMPs and, if applicable, the FDA’s good tissue practices, or GTPs, for the use of human cellular and tissue products to prevent the introduction, transmission, or spread of communicable diseases; • FDA’s audit of clinical trial sites that generated data in support of the BLA; and • FDA approval of a BLA, which must occur before a product can be marketed or sold. 27 Table of Contents Product Development Process Before testing any biologic in humans, the product enters the nonclinical, or preclinical, testing stage.
Figure 5 In initial in vivo studies evaluating the use of direct intramuscular injection of AAV-based constructs with the potential to facilitate the desired silence and replace approach in the A17 transgenic mouse model of OPMD at 11 Table of Contents the Royal Holloway University of London and the Institut de Myologie, we observed decreases in muscle fibrosis, increases in cross sectional area of the treated muscles, decreases in intranuclear inclusions, and normalization of muscle strength.
The mechanism of action of BB-301 is shown in Figure 5. 11 Table of Contents Figure 5 In initial in vivo studies evaluating the use of direct intramuscular injection of AAV-based constructs with the potential to facilitate the desired silence and replace approach in the A17 transgenic mouse model of OPMD at the Royal Holloway University of London and the Institut de Myologie, we observed decreases in muscle fibrosis, increases in cross sectional area of the treated muscles, decreases in intranuclear inclusions, and normalization of muscle strength.
The BB-301 dosing study conducted by the prior BB-301 licensee employed non-ideal routes and methods of BB-301 administration to the target pharyngeal muscle tissues and employed similarly limited analytical methods at the completion of the dosing phase of the study.
The BB-301 dosing study conducted by the prior BB-301 17 Table of Contents licensee employed non-ideal routes and methods of BB-301 administration to the target pharyngeal muscle tissues and employed similarly limited analytical methods at the completion of the dosing phase of the study.
PABPN1 Silencing (i.e., “target knock-down”) within Pharyngeal Muscle Tissues Finally, it is critical to highlight the key methodological distinctions between the recently completed BB-301 Pilot Dosing Study in Beagle dogs conducted by Benitec (i.e., the study described above) and the prior Beagle dog dosing study carried out independently by the previous BB-301 licensee of Benitec.
Figure 10. PABPN1 Silencing (i.e., “target knock-down”) within Pharyngeal Muscle Tissues Finally, it is critical to highlight the key methodological distinctions between the BB-301 Pilot Dosing Study in Beagle dogs conducted by Benitec (i.e., the study described above) and the prior Beagle dog dosing study carried out independently by the previous BB-301 licensee.
Following the implementation of these methodological modifications, Benitec demonstrated a 248-fold improvement (+24,650%) in BB-301 transduction of the HP muscle and a 111-fold improvement (+11,027%) in BB-301 transduction of the TP muscle relative to the levels of BB-301 transduction observed by the previous BB-301 licensee (Figure 12). 18 Table of Contents Figure 12.
Following the implementation of these methodological modifications, Benitec demonstrated a 248-fold improvement (+24,650%) in BB-301 transduction of the HP muscle and a 111-fold improvement (+11,027%) in BB-301 transduction of the TP muscle relative to the levels of BB-301 transduction observed by the previous BB-301 licensee (Figure 11). Figure 11.
RMATs qualifying for such accelerated approval may be able to satisfy licensing requirements through commitment to post-approval clinical studies as well as real-world data such as patient registries and health record analysis.
RMATs qualifying for such accelerated approval may be able to satisfy licensing requirements through commitment to post-approval clinical studies as well as real-world data such as patient 26 Table of Contents registries and health record analysis.
The Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, permits a patent term extension of up to five years beyond the expiration of the patent. The length of the patent term extension is related to the length of time the biologic is under clinical testing regulatory review.
The Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, permits a PTE of up to five years beyond the expiration of the patent. The length of the PTE issued is related to the length of time the drug substance is under clinical testing and regulatory review during the term of the patent.
BB-301 is a ‘silence and replace’ construct encoding two shmiRs targeting the endogenous PABPN1 (including variants causative of OPMD) internally designated shmiR-13 and shmiR-17, as well as a codon-optimized PABPN1 replacement construct, the transcript of which is not targeted by shmiR-13 and shmiR-17. Both shmiRs and the codon- optimized PABPN1 replacement construct are under the control of a muscle-specific promoter.
BB-301 is a ‘silence and replace’ construct encoding two shmiRs targeting the endogenous PABPN1 (including variants causative of OPMD) internally designated shmiR-13 and shmiR-17, as well as a codon-optimized PABPN1 replacement construct, the transcript of which is not targeted by shmiR-13 and shmiR-17.
More specifically, this family includes claims covering shmiR13 and shmiR17 of BB-301 separately, as well as the full BB-301 ‘knockdown and replacement’ construct.
More specifically, this family includes claims covering shmiR13 and shmiR17 of BB-301 separately and in combination, as well as the full BB-301 ‘silence and replacement’ construct.
The information on, or that can be accessed through, our website is not part of this Annual Report and is not incorporated by reference herein. 36 Table of Contents
The information on, or that can be accessed through, our website is not part of this Annual Report on Form 10-K and is not incorporated by reference herein. 37 Table of Contents
A third patent family, entitled “Methods for Treating Oculopharyngeal Muscular Dystrophy (OPMD) (OPMD family #3)” has been filed to pursue claims which are broadly directed to the ‘silence and replace’ treatment concept for OPMD, relying on RNAi agents to knockdown PABPN1 and replacement with functional PABPN1 which is not targeted by the RNAi agents.
A third patent family, entitled “Methods for Treating Oculopharyngeal Muscular Dystrophy (OPMD) (OPMD family #3)” was filed by Benitec’s former licensee, Axovant Therapeutics, on Benitec’s behalf to pursue claims which are broadly directed to the ‘silence and replace’ treatment concept for OPMD, relying on RNAi agents to knockdown PABPN1 and replacement with functional PABPN1 which is not targeted by the RNAi agents.
This technology has broad application in AAV-based gene therapies; • The capabilities to drive the development of a pipeline of programs focused on chronic diseases with either large patient populations, or rare diseases, which may potentially support the receipt of Orphan Drug Designation, including OPMD; and • A growing portfolio of patents protecting improvements to our ddRNAi, and silence and replace, technology and product candidates through at least 2036, with additional patent life anticipated through at least 2040.
This technology has broad application in AAV-based gene therapies; • The capabilities to drive the development of a pipeline of programs focused on chronic diseases with either large patient populations, or rare diseases, which may potentially support the receipt of Orphan Drug Designation, including OPMD; and • A growing portfolio of patents protecting improvements to our ddRNAi, and silence and replace, technology and product candidates through at least 2044, with potential to extend this patent term beyond 2044 in jurisdictions with patent term extension provisions for pharmaceuticals.
In most countries in which we file, the patent term is 20 years from the earliest date of filing a non-provisional patent application. In the United States, a patent term may be shortened if a patent is terminally disclaimed over another patent or as a result of delays in patent prosecution by the patentee.
In most countries in which we file, the patent term is 20 years from the earliest date of filing a non-provisional (or ‘complete’) patent application. In the United States, a patent term may be shortened if a patent is terminally disclaimed over another patent owned by the same assignee.
In a July 2018 guidance, the FDA announced that it does not expect to grant any additional orphan drug designations to drugs for pediatric subpopulations of common diseases (i.e., diseases or conditions with an overall prevalence of 200,000 or greater).
In a July 2018 guidance, the FDA announced that it does not expect to grant any additional orphan drug designations to drugs for pediatric subpopulations of common diseases (i.e., diseases or conditions with an overall prevalence of 200,000 or greater). Pediatric subpopulation orphan designations that have already been granted will not be affected by this change.
Similar provisions are available in Europe and other jurisdictions to extend the term of a patent that covers an approved biologic although the eligibility requirements for any duration of such extension vary.
Similar provisions are available in Europe and other jurisdictions to extend the term of a patent that covers an approved drug substance, although the eligibility requirements and criteria for calculating the duration of such extensions, vary.
Such intellectual property rights include patents claiming our ddRNAi and silence and replace technologies, as well as know-how and trade secrets related to our product candidates and proprietary technology. ddRNAi-based treatment for OPMD Benitec’s patent portfolio for OPMD includes five patent families relating to shRNA and shmiRs targeting PABPN1 (the causative gene for OPMD), as well as ‘silence and replace’ therapeutics and treatment strategies for OPMD.
Such intellectual property rights include, but are not limited to, patents claiming our proprietary ddRNAi and silence and replace technologies, and specific product candidates employing those technologies, as well as know-how and trade secrets related to our product candidates and proprietary technology. ddRNAi-based treatment for OPMD Benitec’s patent portfolio for OPMD includes five active patent families relating to shRNA and shmiRs targeting PABPN1 (the causative gene for OPMD), ‘silence and replace’ therapeutics and treatment strategies for OPMD, as well as interoperative delivery methods and delivery devices for use in such treatment strategies .
This patent family exists as a PCT application and was filed solely in the name of Benitec. AAV with modified phospholipase domain The Benitec patent portfolio includes a single patent family, entitled “Adeno-associated virus (AAV) with modified phospholipase domain,” which relates to an AAV having a modified phospholipase (PLA2) domain in the capsid.
This patent family proceed as a PCT application, and both the PCT application and the related U.S. priority document were filed solely in the name of Benitec. 22 Table of Contents AAV with modified phospholipase domain The Benitec patent portfolio includes a single patent family, entitled “Adeno-associated virus (AAV) with modified phospholipase domain,” which relates to an AAV having a modified phospholipase (PLA2) domain in the capsid.
We cannot guarantee the availability of the license or that it can be obtained on commercially reasonable terms. Know-How In addition to patent protection of ddRNAi and other technology and our product candidates, we also rely on proprietary know-how that is not patentable or that we elect not to patent, as valuable intellectual property for our business.
Know-How In addition to patent protection of ddRNAi and other technology and our product candidates, we also rely on proprietary know-how that is not patentable or that we elect not to patent, as valuable intellectual property for our business.
This increasingly competitive landscape may compromise the development of our product candidates. 24 Table of Contents Government Regulation As a pharmaceutical and biological product company that wishes to conduct clinical trials and ultimately obtain marketing approval in the United States, we are subject to extensive regulation by the FDA, and other federal, state, and local regulatory agencies.
As a pharmaceutical and biological product company that wishes to conduct clinical trials and ultimately obtain marketing approval in the United States, we are subject to extensive regulation by the FDA, and other federal, state, and local regulatory agencies.
Our principal executive offices are located at 3940 Trust Way, Hayward, California 94545. 35 Table of Contents Re-domiciliation On April 15, 2020, or the Implementation Date, the re-domiciliation, or the Re-domiciliation, of Benitec Biopharma Limited, a public company incorporated under the laws of the State of Western Australia, or Benitec Limited, was completed in accordance with the Scheme Implementation Agreement, as amended and restated as of January 30, 2020, between Benitec Limited and us.
Re-domiciliation On April 15, 2020, or the Implementation Date, the re-domiciliation, or the Re-domiciliation, of Benitec Biopharma Limited, a public company incorporated under the laws of the State of Western Australia, or Benitec Limited, was completed in accordance with the Scheme Implementation Agreement, as amended and restated as of January 30, 2020, between Benitec Limited and us.
Pipeline: Oculopharyngeal Muscular Dystrophy We are developing BB-301 for the treatment of Oculopharyngeal Muscular Dystrophy (OPMD). The Investigational New Drug (IND) application for BB-301 was approved to proceed by the U.S. Food and Drug Administration in June 2023. BB-301 is the lead investigational agent under development by Benitec, and the key attributes of BB-301 are outlined in Figure 3.
Pipeline: Oculopharyngeal Muscular Dystrophy We are developing BB-301 for the treatment of Oculopharyngeal Muscular Dystrophy (OPMD) with moderate dysphagia. The Investigational New Drug (IND) application for BB-301 was approved to proceed by the U.S. Food and Drug Administration in June 2023.
These five families cover the OPMD therapeutic candidate, BB-301, under development at Benitec, treatment strategies for OPMD that silence PABPN1 which is causative for OPMD and replace with functional PABPN1, and Benitec’s AAV patent family which covers the delivery system for BB-301.
These five families cover the OPMD therapeutic candidate, BB-301, under development at Benitec, treatment strategies for OPMD that silence PABPN1 which is causative for OPMD and replace with functional PABPN1, Benitec’s AAV patent family which covers the delivery system for BB-301, and the proprietary injection needle, pre-filled multi-injection device and interoperative method which enable delivery of BB-301 to the pharyngeal muscle of OPMD patients.
Patent extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only one patent applicable to an approved biologic may be extended.
However, PTE cannot extend the term of a patent beyond a total of 14 years from the date of marketing approval for the drug substance and only one patent applicable to an approved drug substance may be extended under PTE.
Pediatric subpopulation orphan designations that have already been granted will not be affected by this change. 32 Table of Contents Patent Term Restoration and Marketing Exclusivity Depending on the timing, duration and specifics of FDA marketing approval of our product candidates, some of our U.S. patents may be eligible for limited patent term extension under the Hatch-Waxman Amendments.
Patent Term Restoration and Marketing Exclusivity Depending on the timing, duration and specifics of FDA marketing approval of our product candidates, some of our U.S. patents may be eligible for limited patent term extension under the Hatch-Waxman Amendments.
Biologics License Application Approval Process In order to obtain approval to market a biologic in the United States, a BLA must be submitted to the FDA that provides data from nonclinical studies and clinical trials and manufacturing information establishing to the 28 Table of Contents FDA’s satisfaction the safety, purity, and potency or efficacy of the investigational product for the proposed indication.
Over the last several years the FDA has issued helpful guidance on development of gene therapy products and shown a willingness to work closely with developers, especially with those working in orphan disease areas. 29 Table of Contents Biologics License Application Approval Process In order to obtain approval to market a biologic in the United States, a BLA must be submitted to the FDA that provides data from nonclinical studies and clinical trials and manufacturing information establishing to the FDA’s satisfaction the safety, purity, and potency or efficacy of the investigational product for the proposed indication.
A patent’s term may be lengthened by a patent term adjustment, which compensates a patentee for administrative delays by the USPTO in granting a patent. The patent term of a European patent is 20 years from its filing date, which, unlike in the United States, is not subject to patent term adjustments.
The patent term of a European patent is 20 years from its complete filing date, which, unlike in the United States, is not subject to patent term adjustments due to delays by the European Patent Office (EPO) or patentee during prosecution.
The term of a patent that covers an FDA-approved biologic may also be eligible for patent term extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory review process.
The term of a patent that covers an FDA-approved drug substance may also be eligible for patent term extension (PTE) as compensation for the portion of the patent term that the patentee is able to commercially exploit the patent due to the lengthy FDA regulatory review process which is required for marketing of the drug substance.
Employees As of June 30, 2023, we had 18 full-time employees, 7 of whom have a Ph.D., 4 have Masters Degrees and 2 have Biotechnology Certificates, for a total of 13 with post-graduate degrees. Of these full-time employees, 13 are engaged in research and development activities and 5 are engaged in finance, legal, human resources, facilities and general management.
Employees As of June 30, 2024, we had 16 full-time employees, 6 of whom have a Ph.D.,4 have Masters Degrees and 2 have biotechnology Certificates, and 1 has an M.D., for a total of 13 with post-graduate degrees.
The modified AAV will be used as the delivery system for the OPMD therapeutic. We are aware of a third party patent directed to AAV vectors that expires in 2026. In the event we receive regulatory marketing approval before the expiration date it may be necessary for us to obtain a license to the patent in order to commercialize.
In the event we receive regulatory marketing approval before the expiration date it may be necessary for us to obtain a license to the patent in order to commercialize. We cannot guarantee the availability of the license or that it can be obtained on commercially reasonable terms.
This patent family exists as a PCT application and was filed solely in the name of Benitec. 21 Table of Contents A fourth patent family, entitled “Methods for Treating Oculopharyngeal Muscular Dystrophy (OPMD) (OPMD family #4)” has been filed to specifically claim the OPMD therapeutic candidate developed by Benitec, BB-301 (described herein).
A fourth patent family, entitled “Methods for Treating Oculopharyngeal Muscular Dystrophy (OPMD) (OPMD family #4)” has been filed to specifically claim the OPMD therapeutic candidate developed by Benitec, BB-301, encompassing the ‘silence and replace’ construct (described herein) packaged with Benitec’s proprietary AAV9 vector having a modified phospholipase (PLA2) domain within its capsid (See following section).
Product Development Process Before testing any biologic in humans, the product enters the nonclinical, or preclinical, testing stage. Nonclinical tests include laboratory evaluations of product chemistry, toxicity, and formulation, as well as animal 26 Table of Contents studies to assess the potential safety and activity of the product.
Nonclinical tests include laboratory evaluations of product chemistry, toxicity, and formulation, as well as animal studies to assess the potential safety and activity of the product. The conduct of nonclinical tests must comply with federal regulations and requirements including GLPs.
None of our employees is represented by any labor union. As of June 30, 2023, 17 employees were located in the United States of America, and 1 employee was located in Australia. Corporate Information We were incorporated as a Delaware corporation on November 22, 2019 and completed the Re-domiciliation April 15, 2020.
Corporate Information We were incorporated as a Delaware corporation on November 22, 2019 and completed the Re-domiciliation April 15, 2020. Our predecessor, Benitec Limited, was incorporated under the laws of Australia in 1995. Our principal executive offices are located at 3940 Trust Way, Hayward, California 94545.
Removed
The mechanism of action of BB-301 is shown in Figure 5.
Added
The first study subject was safely dosed in the BB-301 Phase 1b/2a clinical trial (NCT06185673) in November 2023, and the second study subject was safely dosed in February 2024. BB-301 is the lead investigational agent under development by Benitec, and the key attributes of BB-301 are outlined in Figure 3.
Removed
The claims in this application are not limited to BB-301.
Added
The second study subject was dosed with BB-301 in February 2024. • As of January 2024, 23 subjects had enrolled into the NH study in the United States.
Removed
The conduct of nonclinical tests must comply with federal regulations and requirements including GLPs.
Added
On July 15, 2024 Benitec reported positive interim clinical trial data for the first study subject dosed with BB-301 (i.e., “Subject 1”) in the BB-301 Phase 1b/2a Treatment Study (NCT06185673): Previously Announced 90-Day Post-Dose Interim Clinical Study Results At the 90-day post-dose assessment following the administration of the low-dose of BB-301, Subject 1 demonstrated improvements in key VFSS assessments which correlated with the observation of similar levels of improvement in the Sydney Swallow Questionnaire (SSQ) as compared to the pre-dose average values recorded for Subject 1 during the OPMD Natural History Study, indicating an improvement in swallowing function as reported by Subject 1.
Removed
Over the last several years the FDA has issued helpful guidance on development of gene therapy products and shown a willingness to work closely with developers, especially with those working in orphan disease areas.
Added
Newly Reported 180-Day Post-Dose Interim Clinical Study Results The post-dose average values for Total Pharyngeal Residue (TPR), which represents the total amount of solid food or liquid material remaining in the pharynx after the completion of the first swallow of the bolus, remained meaningfully reduced (i.e., smaller amounts of solid food and liquid material remained in the pharynx after the completion of the first swallow) at the 180-day post-dose assessment following the administration of the low dose of gene therapy BB-301 as compared to the pre-dose average values recorded for Subject 1 during the OPMD Natural History Study.
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In the United States and some foreign jurisdictions, there have been, and likely will continue to be, a number of legislative and regulatory changes and proposed changes regarding the healthcare system directed at broadening 34 Table of Contents the availability of healthcare and containing or lowering the cost of healthcare.
Added
Critically, for three of the four food types evaluated during the radiographic swallowing study assessments for Subject 1, the post-dose average TPR values were lower at the 180-day post-dose assessments than at any point during the 9-month pre-dose observation period comprising the OPMD Natural History Study, with the post-dose average TPR value for the fourth food type being similar to the lowest TPR value observed at any point during the 9-month pre-dose observation period of the OPMD Natural History Study.
Removed
In March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care Education Reconciliation Act, or the ACA, was enacted. The ACA includes measures that have significantly changed, and are expected to continue to significantly change, the way healthcare is financed by both governmental and private insurers.
Added
The Total Score recorded for the Subject-Reported SSQ also demonstrated continued reductions in the Subject’s dysphagic symptoms (i.e., improvements in the Subject’s ability to swallow) at the 180-day post-dose timepoint, with the Total SSQ Score continuing to decline and remaining meaningfully reduced as compared to the pre-dose average value recorded for Subject 1 during the OPMD Natural History Study, indicating a greater improvement in swallowing function as reported by Subject 1.
Removed
Other legislative changes have been proposed and adopted in the United States since the ACA was enacted. In August 2011, the Budget Control Act of 2011, among other things, created measures for spending reductions by Congress.
Added
Importantly, similar to the results observed for the VFSS assessments of TPR, the post-dose average Total SSQ Score was lower at the 180-day post-dose timepoint than at any point during the 9-month pre-dose assessment period of the OPMD Natural History Study.
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A Joint Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s automatic reduction to several government programs.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeAs such, we require licenses and the ability to manufacture large quantities of AAV particles under the FDA’s current good manufacturing practices, or cGMP, requirements and those of comparable foreign regulatory authorities in order to commercialize a product candidate using an AAV vector. 44 Table of Contents We may find it difficult to enroll patients in any future clinical trials, and patients could discontinue their participation in our current and any future clinical trials, which could delay or prevent our current and any future clinical trials of our product candidates and make those trials more expensive to undertake.
Biggest changeWe use AAV vectors as part of our ddRNAi and silence and replace approaches for several indications. As such, we require licenses and the ability to manufacture large quantities of AAV particles under the FDA’s current good manufacturing practices, or cGMP, requirements and those of comparable foreign regulatory authorities in order to commercialize a product candidate using an AAV vector.
We expect that we will be subject to additional risks related to engaging in international operations, including: • different regulatory requirements for approval of biopharmaceutical products in foreign countries; • reduced protection for intellectual property rights; • unexpected changes in tariffs, trade barriers and regulatory requirements; • economic weakness, including inflation, or political instability in particular foreign economies and markets; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; • workforce uncertainty in countries where labor unrest is more common than in Australia or the United States; 60 Table of Contents • production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and • business interruptions resulting from geopolitical actions, including war and terrorism, natural disasters, including earthquakes, typhoons, floods and fires and disease pandemics and epidemics.
We expect that we will be subject to additional risks related to engaging in international operations, including: • different regulatory requirements for approval of biopharmaceutical products in foreign countries; • reduced protection for intellectual property rights; • unexpected changes in tariffs, trade barriers and regulatory requirements; • economic weakness, including inflation, or political instability in particular foreign economies and markets; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; 60 Table of Contents • workforce uncertainty in countries where labor unrest is more common than in Australia or the United States; • production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and • business interruptions resulting from geopolitical actions, including war and terrorism, natural disasters, including earthquakes, typhoons, floods and fires and disease pandemics and epidemics.
The applicable federal, state and foreign healthcare laws and regulations that may affect our ability to operate include, but are not limited to, the following: • the federal Anti-Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under federal and state healthcare programs such as Medicare and Medicaid; • federal civil and criminal false claims laws and civil monetary penalty laws, including the federal False Claims Act, which impose criminal and civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, including the Medicare and Medicaid programs, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government; • the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal and civil liability for, among other things, executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, which impose obligations on covered healthcare providers, health plans and healthcare clearinghouses, as well as their business associates that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity, with respect to safeguarding the privacy, security and transmission of individually identifiable health information; • the federal Open Payments program, created under the ACA, and its implementing regulations, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the CMS information related to payments or other transfers of value made to physicians, and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by the physicians and their immediate family members by the 90th day of each subsequent calendar year, and disclosure of such information will be made by CMS on a publicly available website; and • analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payers, including private insurers; state and foreign laws that require biopharmaceutical or biotechnology companies to comply with the industry voluntary 63 Table of Contents compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers; state and foreign laws that require biopharmaceutical or biotechnology manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
The applicable federal, state and foreign healthcare laws and regulations that may affect our ability to operate include, but are not limited to, the following: • the federal Anti-Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under federal and state healthcare programs such as Medicare and Medicaid; • federal civil and criminal false claims laws and civil monetary penalty laws, including the federal False Claims Act, which impose criminal and civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, including the Medicare and Medicaid programs, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government; • the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal and civil liability for, among other things, executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, which impose obligations on covered healthcare providers, health plans and healthcare clearinghouses, as well as their business associates that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity, with respect to safeguarding the privacy, security and transmission of individually identifiable health information; • the federal Open Payments program, created under the ACA, and its implementing regulations, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the CMS information related to payments or other transfers of value made to physicians, and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by the physicians and their immediate family members by the 90th day of each subsequent calendar year, and disclosure of such information will be made by CMS on a publicly available website; and • analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payers, including private insurers; state and foreign laws 63 Table of Contents that require biopharmaceutical or biotechnology companies to comply with the industry voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers; state and foreign laws that require biopharmaceutical or biotechnology manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Disputes may arise regarding intellectual property subject to a licensing agreement, including: • the scope of rights granted under the license agreement and other interpretation-related issues; • the extent to which our technology and processes infringe on intellectual property of a licensor that is not subject to the licensing agreement; • the sublicensing of patent and other rights under any collaborative relationships we might enter into in the future; 72 Table of Contents • our diligence obligations under the license agreement and what activities satisfy those diligence obligations; • the ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners; and • the priority of invention of patented technology.
Disputes may arise regarding intellectual property subject to a licensing agreement, including: • the scope of rights granted under the license agreement and other interpretation-related issues; • the extent to which our technology and processes infringe on intellectual property of a licensor that is not subject to the licensing agreement; • the sublicensing of patent and other rights under any collaborative relationships we might enter into in the future; • our diligence obligations under the license agreement and what activities satisfy those diligence obligations; • the ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners; and 72 Table of Contents • the priority of invention of patented technology.
Our ability to generate future revenues from commercializing product candidates depends heavily on our success in: • establishing proof of concept in preclinical studies and clinical trials for our product candidates; • successfully initiating and completing clinical trials of our product candidates; 38 Table of Contents • obtaining regulatory and marketing approvals for product candidates for which we complete clinical trials; • maintaining, protecting and expanding our intellectual property portfolio, and avoiding infringing on intellectual property of third parties; • establishing and maintaining successful licenses, collaborations and alliances with third parties; • developing a sustainable, scalable, reproducible and transferable manufacturing process for our product candidates; • establishing and maintaining supply and manufacturing relationships with third parties that can provide products and services adequate, in amount and quality, to support clinical development and commercialization of our product candidates, if approved; • launching and commercializing any product candidates for which we obtain regulatory and marketing approval, either by collaborating with a partner or, if launched independently, by establishing a sales, marketing and distribution infrastructure; • obtaining market acceptance of any product candidates that receive regulatory approval as viable treatment options; • obtaining favorable coverage and reimbursement rates for our products from third-party payers; • addressing any competing technological and market developments; • identifying and validating new product candidates; and • negotiating favorable terms in any collaboration, licensing or other arrangements into which we may enter.
Our ability to generate future revenues from commercializing product candidates depends heavily on our success in: • establishing proof of concept in preclinical studies and clinical trials for our product candidates; • successfully initiating and completing clinical trials of our product candidates; 39 Table of Contents • obtaining regulatory and marketing approvals for product candidates for which we complete clinical trials; • maintaining, protecting and expanding our intellectual property portfolio, and avoiding infringing on intellectual property of third parties; • establishing and maintaining successful licenses, collaborations and alliances with third parties; • developing a sustainable, scalable, reproducible and transferable manufacturing process for our product candidates; • establishing and maintaining supply and manufacturing relationships with third parties that can provide products and services adequate, in amount and quality, to support clinical development and commercialization of our product candidates, if approved; • launching and commercializing any product candidates for which we obtain regulatory and marketing approval, either by collaborating with a partner or, if launched independently, by establishing a sales, marketing and distribution infrastructure; • obtaining market acceptance of any product candidates that receive regulatory approval as viable treatment options; • obtaining favorable coverage and reimbursement rates for our products from third-party payers; • addressing any competing technological and market developments; • identifying and validating new product candidates; and • negotiating favorable terms in any collaboration, licensing or other arrangements into which we may enter.
Our ability to recognize revenues from successful potential collaborations may be impaired by multiple factors including: • a collaborator may shift its priorities and resources away from our programs due to a change in business strategies, or a merger, acquisition, sale or downsizing of its company or business unit; • a collaborator may cease development in an area that is the subject of a collaboration agreement; • a collaborator may change the success criteria for a particular program or product candidate in development, thereby delaying or ceasing development of such program or product candidate in development; • a collaborator with development or commercialization obligations may not commit sufficient financial or human resources to the development, marketing, distribution or sale of a product, or may otherwise fail in development or commercialization efforts; • a collaborator with manufacturing responsibilities may encounter regulatory, resource or quality issues and be unable to meet demand requirement; • a collaborator could independently develop, or develop with unrelated parties, products that compete directly or indirectly with our product candidates; • a collaborator may exercise its rights under the agreement to discontinue our collaboration; • a dispute may arise between us and a collaborator concerning the development or commercialization of a product candidate, resulting in a delay in milestones, royalty payments, or discontinuation of a program and possibly resulting in costly litigation or arbitration that may divert management attention and resources; • a collaborator may not adequately protect the intellectual property rights associated with a product candidate; 53 Table of Contents • a collaborator may use our proprietary information or intellectual property in such a way as to expose us actual or threatened litigation from a third party, patent office proceedings or other risks that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential liability; and • a collaborator may own or co-own, or have a license to use, intellectual property rights associated with a product candidate that results from our collaborating with them, and in such cases, we would not have the exclusive right to commercialize such intellectual property rights.
Our ability to recognize revenues from successful potential collaborations may be impaired by multiple factors including: • a collaborator may shift its priorities and resources away from our programs due to a change in business strategies, or a merger, acquisition, sale or downsizing of its company or business unit; • a collaborator may cease development in an area that is the subject of a collaboration agreement; • a collaborator may change the success criteria for a particular program or product candidate in development, thereby delaying or ceasing development of such program or product candidate in development; • a collaborator with development or commercialization obligations may not commit sufficient financial or human resources to the development, marketing, distribution or sale of a product, or may otherwise fail in development or commercialization efforts; • a collaborator with manufacturing responsibilities may encounter regulatory, resource or quality issues and be unable to meet demand requirement; • a collaborator could independently develop, or develop with unrelated parties, products that compete directly or indirectly with our product candidates; • a collaborator may exercise its rights under the agreement to discontinue our collaboration; • a dispute may arise between us and a collaborator concerning the development or commercialization of a product candidate, resulting in a delay in milestones, royalty payments, or discontinuation of a program and possibly resulting in costly litigation or arbitration that may divert management attention and resources; • a collaborator may not adequately protect the intellectual property rights associated with a product candidate; • a collaborator may use our proprietary information or intellectual property in such a way as to expose us actual or threatened litigation from a third party, patent office proceedings or other risks that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential liability; and • a collaborator may own or co-own, or have a license to use, intellectual property rights associated with a product candidate that results from our collaborating with them, and in such cases, we would not have the exclusive right to commercialize such intellectual property rights.
Some specific factors that could negatively affect the price of our common stock or result in fluctuations in its price and trading volume include: • results of our clinical trials; • regulatory actions; • actual or expected fluctuations in our operating results; • changes in market valuations of similar companies; • changes in our key personnel; • changes in financial estimates or recommendations by securities analysts; • strategic decisions by us or our competitors, such as acquisitions, collaborations, divestitures, spin-offs, joint ventures, strategic investments or changes in business strategy; • the passage of legislation or other regulatory developments in the United States and other countries affecting us or our industry; • changes in trading volume of our common stock on Nasdaq; 78 Table of Contents • sales of our common stock by us, our executive officers or our shareholders in the future; and • conditions in the financial markets or changes in general economic conditions.
Some specific factors that could negatively affect the price of our common stock or result in fluctuations in its price and trading volume include: • results of our clinical trials; • regulatory actions; • actual or expected fluctuations in our operating results; • changes in market valuations of similar companies; • changes in our key personnel; • changes in financial estimates or recommendations by securities analysts; 78 Table of Contents • strategic decisions by us or our competitors, such as acquisitions, collaborations, divestitures, spin-offs, joint ventures, strategic investments or changes in business strategy; • the passage of legislation or other regulatory developments in the United States and other countries affecting us or our industry; • changes in trading volume of our common stock on Nasdaq; • sales of our common stock by us, our executive officers or our stockholders in the future; and • conditions in the financial markets or changes in general economic conditions.
In addition, failure to comply with FDA and non-U.S. regulatory requirements may, either before or after product approval, if any, subject us to administrative or judicially imposed sanctions, including: • restrictions on our ability to conduct clinical trials, including full or partial clinical holds on ongoing or planned trials; • restrictions on the products, manufacturers, or manufacturing process; • warning letters; • civil and criminal penalties; • injunctions; • suspension or withdrawal of regulatory approvals; • product seizures, detentions or import bans; • voluntary or mandatory product recalls and publicity requirements; • total or partial suspension of production; • imposition of restrictions on operations, including costly new manufacturing requirements; and • refusal to approve pending BLAs or supplements to approved BLAs.
In addition, failure to comply with FDA and non-U.S. regulatory requirements may, either before or after product approval, if any, subject us to administrative or judicially imposed sanctions, including: • restrictions on our ability to conduct clinical trials, including full or partial clinical holds on ongoing or planned trials; • restrictions on the products, manufacturers, or manufacturing process; • warning letters; 43 Table of Contents • civil and criminal penalties; • injunctions; • suspension or withdrawal of regulatory approvals; • product seizures, detentions or import bans; • voluntary or mandatory product recalls and publicity requirements; • total or partial suspension of production; • imposition of restrictions on operations, including costly new manufacturing requirements; and • refusal to approve pending BLAs or supplements to approved BLAs.
Patient enrollment is affected by factors including: • finding and diagnosing patients; • severity of the disease under investigation; • design of the clinical trial protocol; • size and nature of the patient population; • eligibility criteria for the trial in question; • perceived risks and benefits of the product candidate under study; • proximity and availability of clinical trial sites for prospective patients; • availability of competing therapies and clinical trials; • clinicians’ and patients’ perceptions of the potential advantages of the product being studied in relation to other available therapies, including any new products that may be approved for the indications we are investigating; • patient referral practices of physicians; • ability to monitor patients adequately during and after treatment; and • the COVID-19 pandemic.
Patient enrollment is affected by factors including: • finding and diagnosing patients; • severity of the disease under investigation; • design of the clinical trial protocol; • size and nature of the patient population; • eligibility criteria for the trial in question; • perceived risks and benefits of the product candidate under study; • proximity and availability of clinical trial sites for prospective patients; • availability of competing therapies and clinical trials; • clinicians’ and patients’ perceptions of the potential advantages of the product being studied in relation to other available therapies, including any new products that may be approved for the indications we are investigating; • patient referral practices of physicians; and • ability to monitor patients adequately during and after treatment.
If we fail to comply with applicable regulatory requirements following approval of any of our product candidates, a regulatory agency may: • issue a warning letter asserting that we are in violation of the law; • seek an injunction or impose civil or criminal penalties or monetary fines; • suspend or withdraw regulatory approval; • suspend any ongoing clinical trials; • refuse to permit government reimbursement of our product by government-sponsored third-party payers; • refuse to approve a pending BLA or supplements to a BLA submitted by us for other indications or new product candidates; • seize our product; or • refuse to allow us to enter into or continue supply contracts, including government contracts.
If we fail to comply with applicable regulatory requirements following approval of any of our product candidates, a regulatory agency may: • issue a warning letter asserting that we are in violation of the law; • seek an injunction or impose civil or criminal penalties or monetary fines; • suspend or withdraw regulatory approval; • suspend any ongoing clinical trials; • refuse to permit government reimbursement of our product by government-sponsored third-party payers; 51 Table of Contents • refuse to approve a pending BLA or supplements to a BLA submitted by us for other indications or new product candidates; • seize our product; or • refuse to allow us to enter into or continue supply contracts, including government contracts.
Any new collaboration may be on terms that are not optimal for us, and we may not be able to maintain any new or existing collaboration if, for example, development or approval of a product 64 Table of Contents candidate is delayed, sales of an approved product candidate do not meet expectations or the collaborator discontinues the collaboration.
Anew collaboration may be on terms that are not optimal for us and we may not be to 64 Table of Contents maintain any new or existing collaboration if, for example, development or approval of a product candidate is delayed, sales of an approved product candidate do not meet expectations or the collaborator discontinues the collaboration.
The price of our common stock may decline, which means you may experience a decrease in the value of your shares of our common stock regardless of our operating performance or prospects. In the past, following periods of volatility in the market price of a company’s securities, shareholders often instituted securities class action litigation against that company.
The price of our common stock may decline, which means you may experience a decrease in the value of your shares of our common stock regardless of our operating performance or prospects. In the past, following periods of volatility in the market price of a company’s securities, stockholders often instituted securities class action litigation against that company.
In the event that any of our suppliers or manufacturers fails to comply with such requirements or to perform its obligations to us in relation to quality, timing or otherwise, or if our supply of components or other materials becomes limited or interrupted for other reasons, we may be forced to manufacture the materials ourselves or enter into an agreement with another third party, which would be costly and delay any future clinical trials.
In the event that any of our suppliers or manufacturers fails to comply with such requirements or to perform its obligations to us in relation to quality, timing or otherwise, or if our supply of components or other 55 Table of Contents materials becomes limited or interrupted for other reasons, we may be forced to manufacture the materials ourselves or enter into an agreement with another third party, which would be costly and delay any future clinical trials.
Any future determination to declare cash dividends will be made at the discretion of our Board, subject to compliance with applicable laws and covenants under current or future credit facilities, which may restrict or limit our ability to pay dividends, and will depend on our financial condition, operating results, capital requirements, general business conditions and other factors that our Board may deem relevant.
Any future determination to declare cash dividends will be made at the discretion of our Board, subject to compliance with applicable laws and covenants under current or future credit facilities, which may restrict or limit our ability to pay dividends, and will depend on our financial condition, operating results, capital requirements, general business conditions and other factors that our Board may deem 80 Table of Contents relevant.
We do 37 Table of Contents not expect to generate any significant revenue for the foreseeable future, and we expect to incur significant operating losses for the foreseeable future due to the cost of research and development, preclinical studies and clinical trials and the regulatory approval process for product candidates.
We do 38 Table of Contents not expect to generate any significant revenue for the foreseeable future, and we expect to incur significant operating losses for the foreseeable future due to the cost of research and development, preclinical studies and clinical trials and the regulatory approval process for product candidates.
Moreover, the terms of any financing may adversely affect the holdings or the rights of our shareholders, and the issuance of additional securities, whether equity or debt, by us, or the possibility of such issuance, may cause the market price of our common stock to decline.
Moreover, the terms of any financing may adversely affect the holdings or the rights of our stockholders, and the issuance of additional securities, whether equity or debt, by us, or the possibility of such issuance, may cause the market price of our common stock to decline.
Approval policies, regulations or the type and amount of clinical data necessary to gain marketing approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions, and there may be varying interpretations of data obtained from preclinical studies or clinical trials, any of which may cause delays or limitations in the marketing approval or the decision not to approve an application.
Approval policies, regulations or the type and amount of clinical data necessary to gain marketing approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions, and there may be varying interpretations of data obtained from preclinical studies or clinical trials, any of which may cause 42 Table of Contents delays or limitations in the marketing approval or the decision not to approve an application.
Events that may prevent successful or timely completion of clinical development include: • inability to generate sufficient preclinical, toxicology or other data to support the initiation of human clinical trials; • delays in reaching consensus with regulatory agencies on trial design; • identifying, recruiting and training suitable clinical investigators; • delays in reaching agreement on acceptable terms with prospective CROs and clinical trial sites; • delays in obtaining required IRB or IBC approval at each clinical trial site; • delays in recruiting suitable patients to participate in our clinical trials; • imposition of a clinical hold by regulatory agencies, including after an inspection of our clinical trial operations or trial sites; • failure by our CROs, other third parties or us to adhere to clinical trial requirements; • failure to perform in accordance with the FDA’s good clinical practices, or GCP, or applicable regulatory requirements in other countries; • inability to manufacture, test, release, import or export for use sufficient quantities of our product candidates for use in clinical trials; • failure to manufacture our product candidate in accordance with cGMP requirements or applicable regulatory guidelines in other countries; • delays in the testing, validation and manufacturing of our product candidates; • delays in the delivery of our product candidates to the clinical trial sites; • delays in having patients complete participation in a trial or return for post-treatment follow-up; • clinical trial sites dropping out of a trial; • occurrence of serious adverse events associated with the product candidate that are viewed to outweigh its potential benefits; • changes in regulatory requirements and guidance that require amending or submitting new clinical trial protocols; 46 Table of Contents • clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or discontinue product development programs; or • the severity, duration and impact of the COVID-19 pandemic.
Events that may prevent successful or timely completion of clinical development include: • inability to generate sufficient preclinical, toxicology or other data to support the initiation of human clinical trials; • delays in reaching consensus with regulatory agencies on trial design; • identifying, recruiting and training suitable clinical investigators; • delays in reaching agreement on acceptable terms with prospective CROs and clinical trial sites; • delays in obtaining required IRB or IBC approval at each clinical trial site; • delays in recruiting suitable patients to participate in our clinical trials; • imposition of a clinical hold by regulatory agencies, including after an inspection of our clinical trial operations or trial sites; • failure by our CROs, other third parties or us to adhere to clinical trial requirements; • failure to perform in accordance with the FDA’s good clinical practices, or GCP, or applicable regulatory requirements in other countries; • inability to manufacture, test, release, import or export for use sufficient quantities of our product candidates for use in clinical trials; • failure to manufacture our product candidate in accordance with cGMP requirements or applicable regulatory guidelines in other countries; • delays in the testing, validation and manufacturing of our product candidates; • delays in the delivery of our product candidates to the clinical trial sites; • delays in having patients complete participation in a trial or return for post-treatment follow-up; • clinical trial sites dropping out of a trial; • occurrence of serious adverse events associated with the product candidate that are viewed to outweigh its potential benefits; • changes in regulatory requirements and guidance that require amending or submitting new clinical trial protocols; • clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or discontinue product development programs.
In that event, we likely would be required to limit the size and scope of one or more of our independent programs or increase our expenditures and seek additional funding, which may not be available on acceptable terms or at all, and our business may be harmed. We rely on third parties to conduct our preclinical studies and clinical trials.
In that event, we likely would be required to limit the size and scope of one or more of our independent programs or increase our expenditures and seek additional funding, which may not be available on acceptable terms or at all, and our business may be harmed. 54 Table of Contents We rely on third parties to conduct our preclinical studies and clinical trials.
For example, the AAV vector and related capsid protein, which we are currently using to deliver many of our ddRNAi and silence and replace product candidates, could cause adverse immunological side effects due to preexisting and/or recall responses to the naturally occurring virus from which the vector is engineered, or to the DNA construct product itself.
For example, the AAV vector and related capsid protein, which we are currently using to deliver many of our ddRNAi and silence and replace product candidates, could cause adverse immunological side effects due to 48 Table of Contents preexisting and/or recall responses to the naturally occurring virus from which the vector is engineered, or to the DNA construct product itself.
Satisfaction of the marketing approval requirements typically takes several years and the time needed to satisfy them may vary substantially, based on 41 Table of Contents the type, complexity and novelty of the biopharmaceutical product. We cannot predict if or when we might receive regulatory approvals for any of our product candidates currently under development.
Satisfaction of the marketing approval requirements typically takes several years and the time needed to satisfy them may vary substantially, based on the type, complexity and novelty of the biopharmaceutical product. We cannot predict if or when we might receive regulatory approvals for any of our product candidates currently under development.
In either case, such a license may not be available on commercially reasonable terms or at all. Parties making claims against us may obtain injunctive or other equitable relief, which could effectively block our ability to further develop and commercialize one or more of our product candidates.
In either case, such a license may not be available on commercially reasonable terms or at all. 73 Table of Contents Parties making claims against us may obtain injunctive or other equitable relief, which could effectively block our ability to further develop and commercialize one or more of our product candidates.
Other elements to assure safe use in a mandated REMS could include, but are not limited to, restrictions upon distribution and prescribing, additional prescriber training, establishment of patient registries and other measures that could limit commercialization of the product. Comparable foreign regulating authorities might require adoption of measures similar to a 48 Table of Contents REMS.
Other elements to assure safe use in a mandated REMS could include, but are not limited to, restrictions upon distribution and prescribing, additional prescriber training, establishment of patient registries and other measures that could limit commercialization of the product. Comparable foreign regulating authorities might require adoption of measures similar to a REMS.
Obtaining foreign regulatory approvals and compliance with foreign regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction of our product candidates in certain countries. 51 Table of Contents Further, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries.
Obtaining foreign regulatory approvals and compliance with foreign regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction of our product candidates in certain countries. Further, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries.
It is possible that defects of form in the preparation or filing of our patents or patent applications may exist, or may arise in the future, for example with respect to proper priority claims, inventorship, claim scope, patent term adjustments, etc., although we are unaware of any such defects.
It is possible that defects of form in the preparation or filing of our patents or patent applications may exist, or may arise in the future, for example 69 Table of Contents with respect to proper priority claims, inventorship, claim scope, patent term adjustments, etc., although we are unaware of any such defects.
Because patent applications can take many years to issue, there may be currently pending patent applications which may later result in issued patents that our product candidates may be accused of infringing. In addition, third parties may obtain patents in 73 Table of Contents the future and claim that use of our technologies infringes upon these patents.
Because patent applications can take many years to issue, there may be currently pending patent applications which may later result in issued patents that our product candidates may be accused of infringing. In addition, third parties may obtain patents in the future and claim that use of our technologies infringes upon these patents.
There are situations in which non-compliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. 76 Table of Contents Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.
There are situations in which non-compliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.
Separately, in response to the COVID-19 pandemic, the FDA postponed most inspections of foreign manufacturing facilities and products, postponed routine surveillance inspections of domestic manufacturing facilities and is conducting only teleconference meetings. Regulatory authorities outside the United States may adopt similar restrictions or other policy measures in response to the COVID-19 pandemic.
Separately, in response to the COVID-19 pandemic, the FDA postponed most inspections of foreign manufacturing facilities and products, postponed routine surveillance inspections of domestic manufacturing facilities and is conducting only teleconference meetings. Regulatory authorities in the United States and outside the United States may adopt similar restrictions or other policy measures in response to any future similar events.
We 57 Table of Contents will be competing with many companies that currently have extensive and well- funded marketing and sales operations to recruit, hire, train and retain marketing and sales personnel. We also face competition in our search for third parties to assist us with the sales and marketing efforts of our product candidates.
We will be competing with many companies that currently have extensive and well- funded marketing and sales operations to recruit, hire, train and retain marketing and sales personnel. We also face competition in our search for third parties to assist us with the sales and marketing efforts of our product candidates.
In addition, in an infringement proceeding, a court may decide that a patent of ours or our licensors is not valid, is unenforceable or is not infringed, or may refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question.
In addition, in an infringement proceeding, a court may decide that a patent of ours or our licensors is not valid, is unenforceable or is not infringed, or may refuse to stop the other party from using the technology at issue on the 74 Table of Contents grounds that our patents do not cover the technology in question.
If we seek equity financing we may need to use a significant percentage of our unreserved authorized shares of common stock in such an offering, and would therefore need stockholder approval to implement an increase in 80 Table of Contents our authorized shares of common stock or a reverse stock split in order to issue additional shares of common stock in the future.
If we seek equity financing we may need to use a significant percentage of our unreserved authorized shares of common stock in such an offering, and would therefore need stockholder approval to implement an increase in our authorized shares of common stock or a reverse stock split in order to issue additional shares of common stock in the future.
Despite these contractual provisions, the need to share trade secrets and other confidential information increases the risk that such trade secrets become known by potential competitors, are inadvertently incorporated into the technology of others, or 56 Table of Contents are disclosed or used in violation of these agreements.
Despite these contractual provisions, the need to share trade secrets and other confidential information increases the risk that such trade secrets become known by potential competitors, are inadvertently incorporated into the technology of others, or are disclosed or used in violation of these agreements.
Any significant efforts at the federal or state levels to reform the healthcare system by 61 Table of Contents changing the way healthcare is provided or funded—including through the expansion of Medicare to larger sections of the population—could have a material impact on our business.
Any significant efforts at the federal or state levels to reform the healthcare system by changing the way healthcare is provided or funded—including through the expansion of Medicare to larger sections of the population—could have a material impact on our business.
We compete with a variety of multinational pharmaceutical companies and specialized biotechnology companies, as well as technology being developed at universities and other research institutions. Our competitors have developed, are developing or could develop product candidates and processes competitive with our product candidates.
We compete with a variety of multinational pharmaceutical companies and specialized biotechnology companies, as well as technology being developed at universities and other research institutions. Our competitors have developed, are 59 Table of Contents developing or could develop product candidates and processes competitive with our product candidates.
These market participants may be hesitant to adopt a novel treatment based on ddRNAi or silence and replace technology, and we may not be able to convince the medical community and third-party payers to accept and use, or to provide favorable reimbursement for, any product candidates developed by us or our existing or future collaborators.
These market participants may be hesitant to adopt a novel treatment based on ddRNAi or silence and replace technology, and we may not be able 58 Table of Contents to convince the medical community and third-party payers to accept and use, or to provide favorable reimbursement for, any product candidates developed by us or our existing or future collaborators.
We cannot commercialize a product until the appropriate regulatory authorities have reviewed and approved the product candidate. Even if our product candidates demonstrate safety and efficacy in clinical trials, the regulatory 49 Table of Contents agencies may not complete their review processes in a timely manner, or we may not be able to obtain regulatory approval.
We cannot commercialize a product until the appropriate regulatory authorities have reviewed and approved the product candidate. Even if our product candidates demonstrate safety and efficacy in clinical trials, the regulatory agencies may not complete their review processes in a timely manner, or we may not be able to obtain regulatory approval.
Our and our collaborators’ research methodology may be unsuccessful in identifying potential product candidates, our potential product candidates may not demonstrate the necessary preclinical outcomes to progress to clinical studies, or our product candidates may be shown to have harmful side effects or may have other characteristics that may make the products unmarketable or unlikely to receive marketing approval.
Our and our collaborators’ research methodology may be unsuccessful in identifying potential product candidates, our potential product candidates 52 Table of Contents may not demonstrate the necessary preclinical outcomes to progress to clinical studies, or our product candidates may be shown to have harmful side effects or may have other characteristics that may make the products unmarketable or unlikely to receive marketing approval.
Other than as provided for in our collaboration agreements, we have no control over the resources, time and effort that our collaborators may devote to the development of product candidates.
Other than as provided for in our collaboration agreements, we have no control over the resources, time and effort that our collaborators may devote to the development of product 53 Table of Contents candidates.
These products may compete with our product candidates, if approved, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.
These products may compete with our product candidates, if approved, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. 77 Table of Contents Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.
If the results of our current or any future clinical trials are inconclusive or if there are safety concerns or adverse events associated with our product candidates, we may: • fail to obtain, or be delayed in obtaining, marketing approval for our product candidates; • obtain approval for indications or patient populations that are not as broad as intended or desired; • obtain approval with labeling that includes significant use or distribution restrictions or safety warnings; • need to change the way the product is administered; • be required to perform additional clinical trials to support approval or be subject to additional post- marketing testing requirements; • have regulatory authorities withdraw their marketing approval of the product after granting it; • have regulatory authorities impose restrictions on distribution of the product in the form of a risk evaluation and mitigation strategy, or REMS, or modified REMS, that limit our ability to commercialize the product; • be subject to the addition of labeling statements, such as warnings or contraindications; • be sued and held liable for harm caused to patients; or • experience damage to our reputation. 47 Table of Contents Any of these events could prevent us from achieving or maintaining market acceptance of our product candidates and impair our ability to commercialize our product candidates.
If the results of our current or any future clinical trials are inconclusive or if there are safety concerns or adverse events associated with our product candidates, we may: • fail to obtain, or be delayed in obtaining, marketing approval for our product candidates; • obtain approval for indications or patient populations that are not as broad as intended or desired; • obtain approval with labeling that includes significant use or distribution restrictions or safety warnings; • need to change the way the product is administered; • be required to perform additional clinical trials to support approval or be subject to additional post- marketing testing requirements; • have regulatory authorities withdraw their marketing approval of the product after granting it; • have regulatory authorities impose restrictions on distribution of the product in the form of a risk evaluation and mitigation strategy, or REMS, or modified REMS, that limit our ability to commercialize the product; • be subject to the addition of labeling statements, such as warnings or contraindications; • be sued and held liable for harm caused to patients; or • experience damage to our reputation.
Risks Related to Our Financial Condition, Capital Requirements We have incurred significant losses since inception and anticipate that we will continue to incur losses for the foreseeable future. If we are unable to achieve or sustain profitability, the market value of our common stock will likely decline. As of June 30, 2023, we had accumulated losses of $167.9 million.
Risks Related to Our Financial Condition, Capital Requirements We have incurred significant losses since inception and anticipate that we will continue to incur losses for the foreseeable future. If we are unable to achieve or sustain profitability, the market value of our common stock will likely decline. As of June 30, 2024, we had accumulated losses of $190.3 million.
The success of our business depends primarily upon our ability to identify, develop and commercialize products based on our platform technology. We do not have any products on the market and are early in our development efforts. All of our product candidates are in preclinical development.
The success of our business depends primarily upon our ability to identify, develop and commercialize products based on our platform technology. We do not have any products on the market and are early in our development efforts.
We cannot be certain that such activities by third parties have been or will be conducted in compliance with applicable laws and regulations or will result in valid and enforceable patents and other intellectual property rights.
We cannot be certain that such activities by third parties have 71 Table of Contents been or will be conducted in compliance with applicable laws and regulations or will result in valid and enforceable patents and other intellectual property rights.
While efforts to strike down the ACA in the courts currently seem stalled, uncertainty regarding the future of the ACA remains, including with respect to legislative efforts.
While efforts to strike down the ACA 61 Table of Contents in the courts currently seem stalled, uncertainty regarding the future of the ACA remains, including with respect to legislative efforts.
Therefore, our patents and patent applications may not be prosecuted 69 Table of Contents and enforced in a manner consistent with the best interests of our business.
Therefore, our patents and patent applications may not be prosecuted and enforced in a manner consistent with the best interests of our business.
If we fail to 42 Table of Contents obtain FDA approval to market our product candidates, we will be unable to sell our product candidates in the United States, which will significantly impair our ability to generate revenues.
If we fail to obtain FDA approval to market our product candidates, we will be unable to sell our product candidates in the United States, which will significantly impair our ability to generate revenues.
As a result of COVID-19, we may face increased cybersecurity risks due to our reliance on internet technology and the number of our employees that are working remotely, which may create additional opportunities for cybercriminals to exploit vulnerabilities.
We may face increased cybersecurity risks due to our reliance on internet technology and the number of our employees that are working remotely, which may create additional opportunities for cybercriminals to exploit vulnerabilities.
This risk is material in light of the length of the development process of our products and lifespan of our current patent portfolio. 70 Table of Contents In addition to the protection afforded by patents, we rely on trade secret protection and confidentiality agreements to protect proprietary know-how that is not patentable or that we elect not to patent, processes for which patents are difficult to enforce and any other elements of our product candidate discovery and development processes that involve proprietary know-how, information or technology that is not covered by patents.
In addition to the protection afforded by patents, we rely on trade secret protection and confidentiality agreements to protect proprietary know-how that is not patentable or that we elect not to patent, processes for which patents are difficult to enforce and any other elements of our product candidate discovery and 70 Table of Contents development processes that involve proprietary know-how, information or technology that is not covered by patents.
There can be no assurance that our supply of research and development, preclinical and clinical development biologics and other materials will not be limited, interrupted or restricted in certain geographic regions, be of satisfactory quality or continue to be available at acceptable prices.
We do not own manufacturing facilities or supply sources for such materials. There can be no assurance that our supply of research and development, preclinical and clinical development biologics and other materials will not be limited, interrupted or restricted in certain geographic regions, be of satisfactory quality or continue to be available at acceptable prices.
The investment of our cash and cash equivalents is subject to risks which may cause losses and affect the liquidity of these investments. As of June 30, 2023, we had $2.5 million in cash and cash equivalents.
The investment of our cash and cash equivalents is subject to risks which may cause losses and affect the liquidity of these investments. As of June 30, 2024, we had $50.9 million in cash and cash equivalents.
Such related diagnostics are subject to regulation by the FDA and typically to comparable foreign regulatory authorities as medical devices and typically require separate regulatory approval or clearance prior to commercialization. Marketing approval or clearance of the diagnostic will require sufficient data to support its safety and efficacy.
We may develop related diagnostics for some of our therapeutic product candidates. Such related diagnostics are subject to regulation by the FDA and typically to comparable foreign regulatory authorities as medical devices and typically require separate regulatory approval or clearance prior to commercialization. Marketing approval or clearance of the diagnostic will require sufficient data to support its safety and efficacy.
Risks Related to Commercialization of Our Product Candidates We have not entered into agreements with any third-party manufacturers to support commercialization of our product candidates. We have not yet secured manufacturing capabilities for commercial quantities of our product candidates or established facilities in the desired locations to support commercialization of our product candidates.
We have not yet secured manufacturing capabilities for commercial quantities of our product candidates or established facilities in the desired locations to support commercialization of our product candidates. We intend to rely on third-party manufacturers for commercialization, but have not entered into any agreements with such manufacturers to support our product candidates currently in development.
Implementing any appropriate changes to our internal controls may require specific compliance training of our directors and employees, entail substantial costs in order to modify 79 Table of Contents our existing accounting systems, take a significant period of time to complete and divert management’s attention from other business concerns.
Implementing any appropriate changes to our internal controls may require specific compliance training of our directors and employees, entail substantial costs in order to modify our existing accounting systems, take a significant period of time to complete and divert management’s attention from other business concerns. These changes may not, however, be effective in maintaining the adequacy of our internal control.
Positive results from preclinical studies of our product candidates are not necessarily predictive of the results of our planned clinical trials of our product candidates. Positive results in preclinical proof of concept and animal studies of our product candidates may not result in positive results in clinical trials in humans.
Positive results in preclinical proof of concept and animal studies of our product candidates may not result in positive results in clinical trials in humans.
Competitors may infringe our patents or the patents of our licensors. To counter infringement or unauthorized use, we may be required to file infringement claims, which can be expensive and time-consuming.
To counter infringement or unauthorized use, we may be required to file infringement claims, which can be expensive and time-consuming.
We may be unable to conduct and conclude clinical trials for our product candidate for OPMD if we are unable to raise additional financing.
We may be unable to conduct and conclude clinical trials for our product candidate for OPMD if we are unable to raise additional financing. If we are unable to raise additional funds, and thus unable to continue our studies, our business operations may be adversely affected.
In addition, government funding of other government agencies on which our operations may rely, including those that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable.
Average review times at the agency have fluctuated in recent years as a result. In addition, government funding of other government agencies on which our operations may rely, including those that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable.
Advertising and promotional materials must comply with FDA rules and are subject to FDA review, in addition to other potentially applicable foreign, federal and state laws. 50 Table of Contents In addition, product manufacturers and their establishments, products and applications are subject to payment of user fees/or and continual review and periodic inspections by the FDA and comparable foreign regulatory authorities for compliance with cGMP and comparable foreign requirements, and adherence to commitments made in the BLA.
In addition, product manufacturers and their establishments, products and applications are subject to payment of user fees/or and continual review and periodic inspections by the FDA and comparable foreign regulatory authorities for compliance with cGMP and comparable foreign requirements, and adherence to commitments made in the BLA.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory, and policy changes. Average review times at the agency have fluctuated in recent years as a result.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user 50 Table of Contents fees, and statutory, regulatory, and policy changes.
We cannot guarantee that any clinical trials will be initiated or conducted as planned or completed on schedule, if at all. A failure of one or more clinical trials can occur at any stage of testing.
Clinical trials are expensive and time-consuming, and their outcome is uncertain. We cannot guarantee that any 46 Table of Contents clinical trials will be initiated or conducted as planned or completed on schedule, if at all. A failure of one or more clinical trials can occur at any stage of testing.
Despite our efforts to protect our trade secrets, our competitors may discover our trade secrets, either through breach of these agreements, independent development or publication of information including our trade secrets in cases where we do not have proprietary or otherwise protected rights at the time of publication.
Despite our efforts to protect our trade secrets, our competitors may discover our trade secrets, either through breach of these agreements, independent development or publication of information including our trade secrets in cases where we do not have proprietary or otherwise protected rights at the time of publication. 57 Table of Contents Risks Related to Commercialization of Our Product Candidates We have not entered into agreements with any third-party manufacturers to support commercialization of our product candidates.
In other cases, our licenses are for research purposes only. Upon regulatory marketing approval of our product candidates it may be necessary for us to obtain a broader license in order to commercialize.
In other cases, our licenses are for research purposes only. Upon regulatory marketing approval of our product candidates it may be necessary for us to obtain a broader license in order to commercialize. We cannot guarantee the availability of the broader license or that it can be obtained on commercially reasonable terms.
An important change introduced by the Leahy-Smith Act is that, as of March 16, 2013, the United States transitioned to a “first-to-file” system for deciding which party should be granted a patent when two or more patent applications are filed by different parties claiming the same invention.
The Leahy-Smith Act includes a number of significant changes to U.S. patent law, including provisions that affect the way patent applications will be prosecuted and may also affect patent litigation. 76 Table of Contents An important change introduced by the Leahy-Smith Act is that, as of March 16, 2013, the United States transitioned to a “first-to-file” system for deciding which party should be granted a patent when two or more patent applications are filed by different parties claiming the same invention.
In addition, adverse developments in clinical trials of gene therapy products conducted by others may cause the FDA or comparable foreign regulatory bodies to change the requirements for approval of any of our product candidates. 43 Table of Contents These committees and advisory groups and the new guidelines they promulgate and new requirements they may impose may lengthen the clinical development and regulatory review process, require us to perform additional studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of these product candidates or lead to significant post-approval limitations or restrictions.
These committees and advisory groups and the new guidelines they promulgate and new requirements they may impose may lengthen the clinical development and regulatory review process, require us to perform additional studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of these product candidates or lead to significant post-approval limitations or restrictions.
This increasingly competitive landscape may compromise the development of our product candidates. We are aware of multiple companies that are working in the field of RNAi therapeutics, including Alnylam, Arbutus, Arrowhead. Some of our current product candidates, if approved, would compete with approved and currently marketed treatments.
We are aware of multiple companies that are working in the field of RNAi therapeutics, including Alnylam, Arbutus, and Arrowhead. Some of our current product candidates, if approved, would compete with approved and currently marketed treatments. In addition, our ddRNAi-based product candidates would compete with antisense and other RNA-based pharmaceutical products currently under development.
Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a potential product to market would delay or prevent us from commercializing our product candidates, generating revenues and achieving and sustaining profitability.
Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a potential product to market would delay or prevent us from commercializing our product candidates, generating revenues and achieving and sustaining profitability. 44 Table of Contents Positive results from preclinical studies of our product candidates are not necessarily predictive of the results of our planned clinical trials of our product candidates.
Our ability to successfully initiate, enroll and complete a clinical trial in any foreign country is subject to numerous risks unique to conducting business in foreign countries, including: • difficulty in establishing or managing relationships with contract research organizations, or CROs, clinical sites and physicians; • different standards for the conduct of clinical trials; • our inability to locate and engage qualified local consultants, physicians and partners; and • the potential burden of complying with a variety of foreign laws, medical standards and regulatory requirements, including the regulation of biopharmaceutical and biotechnology products and treatments. 45 Table of Contents In addition, patients enrolled in current and any future clinical trials may discontinue their participation at any time during the trial as a result of a number of factors, including experiencing adverse events, which may or may not be judged related to our product candidates under evaluation.
Our ability to successfully initiate, enroll and complete a clinical trial in any foreign country is subject to numerous risks unique to conducting business in foreign countries, including: • difficulty in establishing or managing relationships with contract research organizations, or CROs, clinical sites and physicians; • different standards for the conduct of clinical trials; • our inability to locate and engage qualified local consultants, physicians and partners; and • the potential burden of complying with a variety of foreign laws, medical standards and regulatory requirements, including the regulation of biopharmaceutical and biotechnology products and treatments.
We urge our investors to consult with their legal and tax advisors regarding the implications of potential changes in U.S. tax laws on an investment in our common stock, warrants and pre-funded warrants.
Future changes in U.S. tax laws could have a material adverse effect on our business, cash flow, financial condition or results of operations. We urge our investors to consult with their legal and tax advisors regarding the implications of potential changes in U.S. tax laws on an investment in our common stock, warrants and pre-funded warrants.
Even if patents covering our product candidates are obtained, once the patent life has expired for a product, we may be open to competition from competitive medications, including biosimilar or generic medications.
Even if patents covering our product candidates are obtained, once the patent life has expired for a product, we may be open to competition from competitive medications, including biosimilar or generic medications. This risk is material in light of the length of the development process of our products and lifespan of our current patent portfolio.
Our reliance on third parties that we do not control does not relieve us of these responsibilities and requirements, and any failure to satisfy these responsibilities and requirements, whether caused by us or by third parties upon whom we rely, could have a material adverse effect on our business, financial condition, results of operations and prospects. 54 Table of Contents Because we rely on third-party manufacturing and supply partners, our supply of research and development, preclinical and clinical development materials may become limited or interrupted or may not be of satisfactory quantity or quality.
Our reliance on third parties that we do not control does not relieve us of these responsibilities and requirements, and any failure to satisfy these responsibilities and requirements, whether caused by us or by third parties upon whom we rely, could have a material adverse effect on our business, financial condition, results of operations and prospects.
In addition, our product candidates are novel, and only one manufacturer currently has experience producing our product candidates on a large scale. If we are unable to engage manufacturing partners to produce our product candidates on a larger scale on reasonable terms, our commercialization efforts will be harmed.
If we are unable to engage manufacturing partners to produce our product candidates on a larger scale on reasonable terms, our commercialization efforts will be harmed.
In addition, if we or our third-party collaborators make significant manufacturing or formulation changes to our product candidates, we or they may need to conduct additional studies to bridge the modified product candidates to earlier versions to ensure comparability, safety and efficacy of the two different product candidates.
Furthermore, many of the factors that lead to a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates. 47 Table of Contents In addition, if we or our third-party collaborators make significant manufacturing or formulation changes to our product candidates, we or they may need to conduct additional studies to bridge the modified product candidates to earlier versions to ensure comparability, safety and efficacy of the two different product candidates.
In addition, principal investigators for our clinical trials may serve as scientific advisors or consultants to us from time to time and may receive cash or equity compensation in connection with such services.
Any of these events could prevent us from achieving or maintaining market acceptance of our product candidates and impair our ability to commercialize our product candidates. In addition, principal investigators for our clinical trials may serve as scientific advisors or consultants to us from time to time and may receive cash or equity compensation in connection with such services.
We have concentrated our product research and development efforts on our ddRNAi technology and silence and replace technology, and our future success depends on successful clinical development of these technologies. We plan to progress our product candidates using our ddRNAi technology and our silence and replace technology for the treatment of the life-threatening conditions of OPMD.
We have concentrated our product research and development efforts on our ddRNAi technology and silence and replace technology, and our future success depends on successful clinical development of these technologies.
There can be no assurance that any development and technical problems we experience in the future will not cause significant delays or unanticipated costs, or that such development problems can be solved.
The scientific evidence to support the feasibility of successfully developing therapeutic treatments based on ddRNAi is preliminary and limited. There can be no assurance that any development and technical problems we experience in the future will not cause significant delays or unanticipated costs, or that such development problems can be solved.
We may not be able to identify, recruit and enroll a sufficient number of patients, or those with required or desired characteristics to achieve diversity in a trial, to complete any future clinical trials in a timely manner.
Clinical trial delays could result in increased costs, slower product development, setbacks in testing the safety and effectiveness of our technology or discontinuation of the clinical trials altogether. 45 Table of Contents We may not be able to identify, recruit and enroll a sufficient number of patients, or those with required or desired characteristics to achieve diversity in a trial, to complete any future clinical trials in a timely manner.
In addition, the trading volume of our common stock may fluctuate and cause significant price variations to occur. If the market price of our common stock declines significantly, you may be unable to resell your shares of our common stock at or above your purchase price, if at all.
If the market price of our common stock declines significantly, you may be unable to resell your shares of our common stock at or above your purchase price, if at all. We cannot assure you that the market price of our common stock will not fluctuate or significantly decline in the future.
If a dispute arises, it may result in costly patent office procedures and litigation, and our collaborator may refuse to pay us while the dispute is ongoing. Furthermore, regardless of any resort to legal action, a dispute with a collaborator over intellectual property rights may damage our relationship with that collaborator and may also harm our reputation in the industry.
Furthermore, regardless of any resort to legal action, a dispute with a collaborator over intellectual property rights may damage our relationship with that collaborator and may also harm our reputation 56 Table of Contents in the industry.
We rely on third-party supply and manufacturing partners to manufacture and supply the materials for our research and development and preclinical and clinical study supplies. We do not own manufacturing facilities or supply sources for such materials.
Because we rely on third-party manufacturing and supply partners, our supply of research and development, preclinical and clinical development materials may become limited or interrupted or may not be of satisfactory quantity or quality. We rely on third-party supply and manufacturing partners to manufacture and supply the materials for our research and development and preclinical and clinical study supplies.
Our or a third party’s failure to execute on our manufacturing requirements could adversely affect our business in a number of ways, including: • an inability to conduct necessary preclinical studies to progress our product candidates to clinical trials; • an inability to initiate or continue any future clinical trials of product candidates under development; • delay in submitting regulatory applications, or receiving regulatory approvals, for product candidates; • loss of the cooperation of a collaborator; • subjecting our product candidates to additional inspections by regulatory authorities; • requirements to cease distribution or to recall batches of our product candidates; and • in the event of approval to market and commercialize a product candidate, an inability to meet commercial demands for our products. 55 Table of Contents Our third-party manufacturers may be subject to damage or interruption from, among other things, events such as the COVID-19 pandemic, fire, natural or man-made disaster, power loss, telecommunications failure, unauthorized entry, computer viruses, denial-of-service attacks, acts of terrorism, human error, vandalism or sabotage, financial insolvency, bankruptcy and similar events.
Our or a third party’s failure to execute on our manufacturing requirements could adversely affect our business in a number of ways, including: • an inability to conduct necessary preclinical studies to progress our product candidates to clinical trials; • an inability to initiate or continue any future clinical trials of product candidates under development; • delay in submitting regulatory applications, or receiving regulatory approvals, for product candidates; • loss of the cooperation of a collaborator; • subjecting our product candidates to additional inspections by regulatory authorities; • requirements to cease distribution or to recall batches of our product candidates; and • in the event of approval to market and commercialize a product candidate, an inability to meet commercial demands for our products.

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Item 2. Properties

Properties — owned and leased real estate

1 edited+0 added−5 removed1 unchanged
Biggest changeWe are not currently a party to any material legal proceedings. Item 4. Mine Safety Disclosures. Not applicable. 82 Table of Contents PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities.
Biggest changeWe are not currently a party to any material legal proceedings. Item 4. Mine Safety Disclosures. Not applicable. 82 Table of Contents PART II
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Market Information Our common stock trades on Nasdaq under the symbol “BNTC.” On August 15, 2023, the closing sale price of our common stock as reported on Nasdaq was $2.69 per share. Holders As of September 10, 2023, we had approximately 3,318 record holders of our common stock.
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The number of record holders is based on the actual number of holders registered on the books of our transfer agent and does not reflect holders of shares in “street name” or persons, partnerships, associations, corporations or other entities identified in security position listings maintained by depository trust companies.
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Dividends We never have declared or paid any cash dividends on our capital stock. Currently, we anticipate that we will retain all available funds for use in the operation and expansion of our business and do not anticipate paying any cash dividends for the foreseeable future.
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Any future determination relating to dividend policy will be made at the discretion of our Board and will depend on our future earnings, capital requirements, financial condition, prospects, applicable Delaware law, which provides that dividends are only payable out of surplus or current net profits, and other factors that our Board deems relevant. Recent Sales of Unregistered Securities None.
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Use of Proceeds Not applicable. Purchases of Equity Securities Not applicable. Item 6. Reserved. 83 Table of Contents

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeDIVIDEND POLICY We never have declared or paid any cash dividends on our capital stock. Currently, we anticipate that we will retain all available funds for use in the operation and expansion of our business and do not anticipate paying any cash dividends for the foreseeable future.
Biggest changeDividends We never have declared or paid any cash dividends on our capital stock. Currently, we anticipate that we will retain all available funds for use in the operation and expansion of our business and do not anticipate paying any cash dividends for the foreseeable future.
Any future determination relating to our dividend policy will be made at the discretion of our Board and will depend on our future earnings, capital requirements, financial condition, prospects, applicable Delaware law, which provides that dividends are only payable out of surplus or current net profits, and other factors that our Board deems relevant.
Any future determination relating to dividend policy will be made at the discretion of our Board and will depend on our future earnings, capital requirements, financial condition, prospects, applicable Delaware law, which provides that dividends are only payable out of surplus or current net profits, and other factors that our Board deems relevant.
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Equity or Equity-Linked Incentive Awards Although we do not have a formal policy with respect to the grant of equity incentive awards to our NEOs, we believe that equity grants provide our NEOs with a strong link to our long-term performance, create an ownership culture and help to align the interests of our NEOs and our stockholders.
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Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. Market Information Our common stock trades on Nasdaq under the symbol “BNTC.” On September 19, 2024, the closing sale price of our common stock as reported on Nasdaq was $8.36 per share.
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On December 9, 2020, the Company’s stockholders approved the Company’s 2020 Equity and Incentive Compensation Plan (the “2020 Plan”).
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Holders As of September 10, 2024, we had approximately 1,416 record holders of our common stock.
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Our Compensation Committee has granted stock options to our NEOs, which have historically been subject to time-based vesting, vesting in increments of one-third on each of the first, second and third anniversaries of the applicable grant date, generally subject to the applicable NEO’s continued employment through the vesting date.
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The number of record holders is based on the actual number of holders registered on the books of our transfer agent and does not reflect holders of shares in “street name” or persons, partnerships, associations, corporations or other entities identified in security position listings maintained by depository trust companies.
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We believe that equity grants with a time-based vesting feature promote executive retention because this feature incentivizes our NEOs to remain in our employment during the vesting period. III-6 Table of Contents On June 13, 2023, the Compensation Committee approved the grant to each of Dr. Banks and Ms.
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Recent Sales of Unregistered Securities On April 22, 2024 we closed a private investment in public equity (PIPE) financing in which we sold 5,749,152 shares of common stock at a price per share of $4.80 and, in lieu of shares of common stock, pre-funded warrants to purchase up to an aggregate of 2,584,239 shares of common stock at a price per pre-funded warrant of $4.7999, to certain accredited institutional investors.
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Boston, of nonqualified stock options to purchase 20,994 and 9,000 shares (reflective of the Reverse Stock Split), respectively, of the Company’s common stock pursuant to the 2020 Plan. The stock options vest in increments of one-third on each of the first, second and third anniversaries of the applicable grant date.
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The pre-funded warrants were immediately exercisable until exercised in full at an exercise price of $0.0001 per share of common stock. Gross proceeds from the financing totaled $40.0 million. Net proceeds, net of commissions and other offering expenses, totaled approximately $37.1 million.
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If an NEO dies or terminates employment or service due to Disability (as defined in the 2020 Plan), the NEO generally has 12 months to exercise their vested options or the options are cancelled.
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The sales of securities in the financing were exempt from registration pursuant to Section 4(a)(2) of the Securities Act and Regulation D thereunder. Use of Proceeds Not applicable. Purchases of Equity Securities Not applicable. Item 6. Reserved. 83 Table of Contents
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If an NEO otherwise leaves the Company, other than for a termination by the Company for Cause (as defined in the 2020 Plan), the NEO generally has 90 days to exercise their vested options or the options are cancelled.
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Upon the consummation of a Change in Control (as defined in the 2020 Plan), all unvested stock options will immediately vest as of immediately prior to the Change in Control. Employment Agreements with our NEOs. We are a party to employment agreements with each of our NEOs.
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These employment agreements provide for “at will” employment and may be terminated at any time. Employment Agreement with Dr. Jerel A. Banks, M.D. Ph.D. In September 2018, Tacere Therapeutics, Inc., a subsidiary of the Company, entered into an employment agreement with Dr. Banks setting forth the terms of his employment as Executive Chairman and Chief Executive Officer of Limited.
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In connection with the Re-Domiciliation, Dr. Banks was appointed Executive Chairman and Chief Executive Officer of the Company. The agreement provides for Dr.
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Banks’ employment and sets forth his (i) annual base salary, (ii) discretionary annual bonus, (iii) eligibility to participate in employee benefit plans, (iv) eligibility for accrued paid vacation, (v) expense reimbursements in accordance with Company policy, (vi) eligibility to participate in the Company’s Share Option Plan (as defined below), (vii) post-employment obligations to refrain from soliciting our employees for one year following the end of employment, and (viii) certain non-disparagement obligations.
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Dr. Banks’ employment agreement also provides for confidentiality of information and ownership of proprietary property restrictions. Pursuant to the employment agreement, Dr. Banks’ employment is “at will” and can be terminated at any time. However, the Company must provide Dr. Banks with at least six months’ prior notice (or pay in lieu of notice) prior to any termination. Dr.
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Banks may terminate his employment on no fewer than six months’ prior written notice to the Company. Notwithstanding any provisions in the employment agreement, the Company may terminate Dr. Banks’ employment immediately without prior notice to Dr.
Removed
Banks if he (a) commits any serious or persistent breach of any of the provisions of the employment agreement, (b) commits any act of willful or serious misconduct or negligence in the discharge of his duties, (c) becomes of unsound mind or under the control of any committee or officer under any law relating to mental health, (d) is convicted of a felony, which in our reasonable opinion affects Dr.
Removed
Banks’ position, or (e) becomes permanently incapacitated by accident or illness from performing duties under the employment agreement for a period aggregating more than three months in any six-month period, or for any period beyond three consecutive months.
Removed
Employment Agreement with Megan Boston In July 2018, Limited entered into an employment agreement with Megan Boston for the position of Executive Director. In connection with entering into the employment agreement, Ms. Boston ceased serving as a Non-Executive Director of the Company. Ms. Boston remains on the Board as an Executive Director. The employment agreement provides for Ms.
Removed
Boston’s employment and sets forth her (i) annual base salary, (ii) discretionary annual bonus, (iii) superannuation contribution, (iv) eligibility for accrued paid vacation, (v) expense reimbursements in accordance with Company policy, and (vi) post-employment obligations to refrain from soliciting our employees for one year following the end of employment. Ms.
Removed
Boston’s employment agreement also provides for confidentiality of information and ownership of proprietary property restrictions. III-7 Table of Contents Pursuant to the employment agreement, Ms. Boston’s employment is “at will” and can be terminated at any time. However, the Company must provide Ms.
Removed
Boston with at least six months’ prior notice (or pay in lieu of notice) prior to any termination. Ms. Boston may terminate her employment on no fewer than six months’ prior written notice. Notwithstanding any provisions in the employment agreement, the Company may terminate Ms. Boston’s employment immediately without prior notice to Ms.
Removed
Boston if she (a) commits any serious or persistent breach of any of the provisions of the employment agreement, (b) commits any act of willful or serious misconduct or negligence in the discharge of her duties, (c) becomes bankrupt or makes any arrangement or composition with her creditors, (d) becomes of unsound mind or under the control of any committee or officer under any law relating to mental health, (e) is convicted of any criminal offense other than an offense which in our reasonable opinion does not affect Ms.
Removed
Boston’s position, or (f) becomes permanently incapacitated by accident or illness from performing her duties under the employment agreement for a period aggregating more than three months in any six-month period, or any period beyond three consecutive months.
Removed
Outstanding Equity Awards at Fiscal Year-End The following table sets forth information regarding outstanding equity or equity-linked awards for each of our NEOs as of June 30, 2023. All amounts are reflective of the Company’s 1-for-17 reverse stock split of the shares of Common Stock, effective July 26, 2023 (the “Reverse Stock Split”).
Removed
Option Awards Named Executive Officer Grant Date Number of Securities Underlying Unexercised Options (#)— Exercisable Number of Securities Underlying Unexercised Options (#)— Unexercisable Option Exercise Price ($) Option Expiration Date Dr. Jerel A. Banks, M.D.
Removed
Ph.D. 6/13/2023(1)(2) — 20,994 3.91 6/13/2033 Executive Chairman and Chief Executive Officer 12/9/2020(1)(2) 11,150 5,576 50.66 12/9/2030 Megan Boston 6/13/2023(1)(2) — 9,000 3.91 6/13/2033 Executive Director 12/9/2020(1)(2) 5,575 2,788 50.66 12/9/2030 3/12/2019(2)(3) 980 — 721.99 3/12/2024 (1) The option awards were granted under the 2020 Plan.
Removed
(2) The shares subject to each of the option awards vest in substantially equal installments on each of the first, second and third anniversaries of the grant date, generally subject to continued employment through the applicable vesting date.
Removed
(3) The option awards were granted under the Benitec Officers’ and Employees’ Share Option Plan prior to the Re-Domiciliation (the “ Share Option Plan ”). The share amounts and exercise prices of the awards shown in this table have been adjusted to reflect the terms of the Re-Domiciliation.
Removed
Other Elements of Compensation Other Benefits and Perquisites We offer participation in broad-based retirement, health and welfare plans to all of our colleagues, including our NEOs. We maintain a tax-qualified defined contribution retirement plan that provides eligible U.S. employees (including Dr. Banks) with an opportunity to save for retirement on a tax-advantaged basis.
Removed
Plan participants are eligible to defer eligible compensation subject to applicable annual Internal Revenue Code limits. The 401(k) III-8 Table of Contents plan is intended to be qualified under Section 401(a) of the Internal Revenue Code with the 401(k) plan’s related trust intended to be tax exempt under Section 501(a) of the Internal Revenue Code.
Removed
As a tax-qualified retirement plan, contributions to the 401(k) plan and earnings on those contributions are not taxable to the employees until distributed from the 401(k) plan. We contribute to the Australian superannuation scheme that provides eligible Australian employees (including Ms. Boston) with an opportunity to save for retirement on a tax-advantaged basis.
Removed
We pay superannuation in accordance with legislative requirements and our minimum contribution is set by legislation. We offer flexibility for salary sacrifice to be added to the superannuation scheme and any actual increase in our contribution to the superannuation scheme is subject to legislative rules at the time.
Removed
Termination or Change in Control Benefits The employment agreements with our NEOs provide for specified notice periods (or pay in lieu of notice) if the Company terminates the employment of our NEOs under certain circumstances, as described above in the “Employment Agreements with our NEOs” section.
Removed
Upon the consummation of a Change in Control (as defined in the 2020 Plan), all unvested stock options granted pursuant to the 2020 Plan will immediately vest as of immediately prior to the Change in Control.
Removed
Our NEOs are not eligible to receive any additional payments or benefits in connection with their termination of employment or in connection with the Company’s change in control.
Removed
Pay Versus Performance Disclosure As required by Item 402(v) of Regulation S-K, which was mandated by Section 953(a) of the Dodd-Frank Act, we are providing the following information about the relationship between “compensation actually paid” to our principal executive officer (“PEO”) and average “compensation actually paid” (“CAP”) to each of our NEOs and the financial performance of the Company for the Company’s fiscal years ended June 30, 2023 (“Fiscal 2023”) and June 30, 2022 (“Fiscal 2022”), in each case calculated in a manner consistent with SEC rules.
Removed
Year Summary Compensation Table Total for PEO(1) Compensation Actually Paid to PEO(1)(2) Average Summary Compensation Table Total for Non-PEO NEOs (2)(3) Average Compensation Actually Paid to Non-PEO NEOs (2)(3) Value of Initial Fixed $100 Investment Based On(4): Net Income (loss) (in thousands) Total Shareholder Return 2023 $ 645,725 $ 428,866 $ 352,529 $ 243,965 $ (79.44 ) $ (14,901 )(5) 2022 $ 799,964 $ (176,698 ) $ 456,476 $ (39,270 ) $ (71.36 ) $ (18,208 ) (1) The PEO reflected in these columns for Fiscal 2023 and Fiscal 2022 is Dr.
Removed
Jerel A. Banks, M.D. Ph.D. (2) CAP to our PEO and Non-PEO NEO (Megan Boston, our Executive Director) is calculated based on the “Total Compensation” reported in the Summary Compensation Table (“SCT”) for each of the applicable fiscal years, adjusted to exclude and include certain items in accordance with Item 402(v) of Regulation S-K as follows.
Removed
PEO SCT Total to CAP Reconciliation: Fiscal Year SCT Total Deductions from SCT Total (i) Additions to SCT Total (ii) CAP Fair Value of Current Year Equity Awards for Fiscal Year 2023 Change in Value of Prior Years’ Awards Unvested for Fiscal Year 2023 Change in Value of Prior Years’ Awards that Vested in Fiscal Year 2023 2023 $ 645,725 $ 70,657 74,271 (230,188 ) 9,715 $ 428,866 2022 $ 799,964 $ 0 0 (867,266 ) (109,396 ) $ (176,698 ) III-9 Table of Contents Average Non-PEO NEOs SCT Total to CAP Reconciliation: Fiscal Year Summary Compensation Table (“SCT”) Total Deductions from SCT(i) Additions to SCT(ii) CAP Fair Value of Current Year Equity Awards for Fiscal Year 2023 Change in Value of Prior Years’ Awards Unvested for Fiscal Year 2023 Change in Value of Prior Years’ Awards that Vested in Fiscal Year 2023 2023 $ 352,529 $ 30,289 31,839 (114,972 ) 4,858 $ 243,965 2022 $ 456,476 $ 0 0 (435,106 ) (60,640 ) $ (39,270 ) (i) Represents the grant date fair value of equity-based awards granted each year as reported in the Summary Compensation Table for the applicable fiscal year.
Removed
The fair values of equity compensation, including such amounts described in the tables above, are calculated in accordance with FASB ASC Topic 718. All assumptions made in the valuations are contained and described in Note 10 to the Company’s consolidated financial statements for the year ended June 30, 2023 included in this Annual Report.
Removed
We did not report a change in pension value for any of the years reflected in this table because the Company does not maintain a defined benefit or actuarial pension plan and therefore a deduction from SCT related to such pension plans is not needed.
Removed
(ii) Reflects the value of equity calculated in accordance with the SEC methodology for determining CAP for each year shown. The fair values of equity compensation, including such amounts described in the tables below, are calculated in accordance with FASB ASC Topic 718.
Removed
The amounts shown in the table reflect the total fair value on the applicable date(s) listed in the table above, and do not necessarily reflect the actual value, if any, that may be realized by the PEO.
Removed
(3) The non-PEO NEO reflected in these columns, and our only non-PEO for the covered fiscal years, is Megan Boston (Executive Director) (4) Represents cumulative total return to holders of our common stock from June 30, 2021 (the last trading day before Fiscal 2022) through June 30, 2023 (the last trading day of the covered period), calculated from the market close on the last trading day before Fiscal 2022 through and including the end of each applicable fiscal year in the table above for which the total shareholder return is being calculated.
Removed
The total shareholder return for each investment assumes that $100 was invested in our common stock and the respective index on June 30, 2021 through June 30, 2023, including reinvestment of any dividends (of which none were paid during this period).
Removed
Relationship Between Financial Performance Measures and CAP In Fiscal 2023, there was an inverse relationship between our total shareholder return compared to our PEO CAP and our average non-PEO NEO CAP, and there was a direct relationship between our net income compared to our PEO CAP and our average non-PEO NEO CAP.
Removed
Our total shareholder return decreased by approximately 11% as compared to Fiscal 2022. Our net income between Fiscal 2022 and Fiscal 2023 decreased by approximately 5%. Our PEO CAP increased by approximately 343% and our average non-PEO NEO CAP increased by approximately 721%, in each case as compared to Fiscal 2022.
Removed
In Fiscal 2022, there was a direct relationship between our total shareholder return and net income, compared to our PEO CAP and average non-PEO NEO CAP, all of which were negative in Fiscal 2022. Our total shareholder return decreased by approximately 42% as compared to Fiscal 2021. Our net income between Fiscal 2021 and Fiscal 2022 decreased by approximately 31%.
Removed
And our PEO CAP and average non-PEO NEO CAP each decreased by approximately 110% and 104%, respectively, as compared to Fiscal 2021. III-10 Table of Contents DIRECTOR COMPENSATION The following table shows the total compensation paid to the Company’s directors (other than any such directors who are also NEOs) for the fiscal year ended June 30, 2023.
Removed
Name Fees Earned or Paid in Cash ($)(2) Option Awards ($)(3) All Other Compensation ($)(4) Total ($) J. Kevin Buchi 64,000 1,777 — 65,777 Peter Francis 60,066 1,777 5,460 67,303 Edward F. Smith 61,208 1,777 — 62,985 (1) For information regarding the compensation of Dr. Banks and Ms. Boston, see “Summary Compensation Table.” (2) Fees paid to Mr.
Removed
Francis were paid in Australian dollars and have been converted to U.S. dollars using a conversion rate of A$1.00 to $0.673 for the fiscal year ended June 30, 2023.
Removed
(3) Amount represents the aggregate grant date fair value of stock and option awards granted by the Company in the fiscal year ended June 30, 2023, computed in accordance with FASB ASC Topic 718.
Removed
For further information on how we account for stock-based compensation, see Note 10 to the Company’s consolidated financial statements for the year ended June 30, 2023 included in this Annual Report. These amounts reflect the Company’s accounting expense for these awards and do not correspond to the actual amounts, if any, that will be recognized by the directors.
Removed
(4) For information regarding other compensation of all directors, see “Narrative Disclosure to Director Compensation Table.” For each director, the aggregate number of option awards outstanding at fiscal year-end for the fiscal year ended June 30, 2023 is set forth below. All amounts below are reflective of the Reverse Stock Split: Name Option Awards (#) J.
Removed
Kevin Buchi 2,798 Peter Francis 2,798 Edward F. Smith 2,798 Narrative Disclosure to Director Compensation Table Upon their appointment as executive officers and employees, Dr. Banks and Ms. Boston no longer receive annual fees with respect to their service on the Board.
Removed
The annual fees for the fiscal year ended June 30, 2023 paid to our non-employee directors were: • an annual cash retainer of $40,000; • an additional annual cash retainer of $15,000 to the chair of the Audit Committee; • an additional annual cash retainer of $10,000 to the chair of the Compensation Committee; • an additional annual cash retainer of $7,500 to the chair of the Nominating Committee; • an additional annual cash retainer of $7,500 to a non-chair member of the Audit Committee; • an additional annual cash retainer of $5,000 to a non-chair member of the Compensation Committee; and • an additional annual cash retainer of $4,000 to a non-chair member of the Nominating Committee.
Removed
III-11 Table of Contents In addition to the cash fees paid to our non-employee directors, the Board granted each of Messrs. Buchi, Francis and Smith seven hundred five (705) option awards (reflective of the Reverse Stock Split) on December 7, 2022.
Removed
The option awards vest in three substantially equal installments on the day prior to each of the Company’s next three annual stockholder meetings occurring immediately following December 7, 2022. In addition, the Company makes a superannuation contribution on Mr. Francis’ behalf in the amount of $5,460.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

37 edited+14 added−15 removed29 unchanged
Biggest changeExpenses The following table sets forth a summary of our expenses for each of the periods set forth below: Year Ended June 30, 2023 2022 (US$’000) Expenses: Royalties and license fees $ — $ 9 Research and development 12,774 11,272 General and administrative 6,382 6,646 Total expenses 19,156 17,927 During the year ended June 30, 2023, we did not incur any royalties and license fees, as compared to $9 thousand for the year ended June 30, 2022.
Biggest changeThe Company also anticipates an increase in expenses relating to accounting, legal and regulatory-related services associated with maintaining compliance with exchange listing and SEC requirements, director and officer insurance premiums and other costs associated with being a domestic public company. 86 Table of Contents Expenses The following table sets forth a summary of our expenses for each of the periods set forth below: Year Ended June 30, 2024 2023 (US$’000) Expenses: Royalties and license fees $ (108 ) $ — Research and development 15,609 12,774 General and administrative 6,989 6,382 Total expenses $ 22,490 $ 19,156 During the years ended June 30, 2024 and June 30, 2023, we incurred royalties and license fees expenses of $(108) thousand and zero, respectively.
The Company records accrued liabilities for estimated costs of research and development activities conducted by third-party service providers, which include the conduct of pre-clinical studies and clinical trials, and contract manufacturing activities.
The Company records accrued liabilities for estimated costs of research and development activities conducted by third-party service providers, which include the conduct of pre-clinical studies and clinical trials, and contract manufacturing activities.
The Company accrues for these costs based on factors such as estimates of the work completed and in accordance with agreements established with its third-party service providers. The Company makes significant judgments and estimates in determining the accrued liabilities balance at the end of each reporting period. As actual costs become known, the Company adjusts its accrued liabilities.
The Company accrues for these costs based on factors such as estimates of the work completed and in accordance with agreements established with its third-party service providers. The Company makes significant judgments and estimates in determining the accrued liabilities balance at the end of each reporting period. As actual costs become known, the Company adjusts its accrued liabilities.
Our future funding requirements will depend on many factors, including, but not limited to: • the timing and costs of our planned clinical trials for our ddRNAi and silence and replace product candidates; • the timing and costs of our planned preclinical studies for our ddRNAi and silence and replace product candidates; 89 Table of Contents • the number and characteristics of product candidates that we pursue; • the outcome, timing and costs of seeking regulatory approvals; • revenue received from commercial sales of any of our product candidates that may receive regulatory approval; • the terms and timing of any future collaborations, licensing, consulting or other arrangements that we may establish; • the amount and timing of any payments we may be required to make, or that we may receive, in connection with the licensing, filing, prosecution, defense and enforcement of any patents or other intellectual property rights; • the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights and defending against intellectual property related claims; and • the extent to which we need to in-license or acquire other products and technologies.
Our future funding requirements will depend on many factors, including, but not limited to: • the timing and costs of our planned clinical trials for our ddRNAi and silence and replace product candidates; • the timing and costs of our planned preclinical studies for our ddRNAi and silence and replace product candidates; • the number and characteristics of product candidates that we pursue; • the outcome, timing and costs of seeking regulatory approvals; • revenue received from commercial sales of any of our product candidates that may receive regulatory approval; • the terms and timing of any future collaborations, licensing, consulting or other arrangements that we may establish; • the amount and timing of any payments we may be required to make, or that we may receive, in connection with the licensing, filing, prosecution, defense and enforcement of any patents or other intellectual property rights; • the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights and defending against intellectual property related claims; and • the extent to which we need to in-license or acquire other products and technologies.
We anticipate that our general and administrative expenses may increase as the Company focuses on the continued development of the pre-clinical OPMD program.
We anticipate that our general and administrative expenses may increase as the Company focuses on the continued development of the clinical OPMD program.
Translation adjustments arising from the use of different exchange rates from period to period are included as a component of stockholders’ equity as “Accumulated other comprehensive income (loss).” Gains and losses resulting from foreign currency transactions are included in the statements of operations and comprehensive income (loss) as other comprehensive income (loss).
Translation adjustments arising from the use of different exchange rates from period to period are included as a component of stockholders’ equity as “Accumulated other comprehensive income (loss).” Gains and losses resulting from foreign currency translation are included in the consolidated statements of operations and comprehensive income (loss) as other comprehensive income (loss).
These uncertainties are discussed in the section above entitled “Risk Factors.” Based on a critical assessment of its accounting policies and the underlying judgments 90 Table of Contents and uncertainties affecting the application of those policies, management believes that the Company’s consolidated financial statements are fairly stated in accordance with accounting principles generally accepted in the United States of America, and provide a meaningful presentation of the Company’s financial condition and results of operations.
These uncertainties are discussed in the section above entitled “Risk Factors.” Based on a critical assessment of its accounting policies and the underlying judgments and uncertainties affecting the application of those policies, management believes that the Company’s consolidated financial statements are fairly stated in accordance with accounting principles generally accepted in the United States of America, and provide a meaningful presentation of the Company’s financial condition and results of operations.
The Company records the estimated costs of research and development activities based 86 Table of Contents upon the estimated amount of services provided but not yet invoiced and includes these costs in trade and other payables on the consolidated balance sheets and within research and development expenses on the consolidated statements of operations and comprehensive loss.
The Company records the estimated costs of research and development activities based upon the estimated amount of services provided but not yet invoiced and includes these costs in trade and other payables on the consolidated balance sheets and within research and development expenses on the consolidated statements of operations and comprehensive loss.
The slight increase in revenues from customers is due to the increase in licensing revenue in the current year. Royalties and license fees Royalties and license fees consist primarily of payments we are required to remit for royalties and other payments related to in-licensed intellectual property.
The decrease in revenues from customers is due to the decrease in licensing revenue in the current year. Royalties and license fees Royalties and license fees consist primarily of payments we are required to remit for royalties and other payments related to in-licensed intellectual property.
The Company received gross proceeds of approximately $17.9 million and net proceeds of approximately $16.0 million from the offering. August 2023 Capital Raise On August 11, 2023, the Company announced the closing of an underwritten public offering of common stock and common stock equivalents (the “August 2023 Capital Raise”).
August 2023 Capital Raise On August 11, 2023, the Company announced the closing of an underwritten public offering of common stock and common stock equivalents (the “August 2023 Capital Raise”). The Company received gross proceeds of approximately $30.9 million and net proceeds of approximately $27.9 million from the offering.
We do not expect to generate revenue from product sales unless and until we obtain regulatory approval of and commercialize one of our current or future product candidates.
We do not know when, or if, we will generate any revenue from product sales. We do not expect to generate revenue from product sales unless and until we obtain regulatory approval of and commercialize one of our current or future product candidates.
The Company received gross proceeds of approximately $30.9 million and net proceeds of approximately $28.6 million from the offering. We have based our projections of operating capital requirements on assumptions that may prove to be incorrect and we may use all of our available capital resources sooner than we expect.
The Company received gross proceeds of approximately $40.0 million and net proceeds of approximately $37.1 million from the offering. We have based our projections of operating capital requirements on assumptions that may prove to be incorrect and we may use all of our available capital resources sooner than we expect.
Contractual Obligations and Commercial Commitments On October 1, 2016, the Company entered into an operating lease for office space in Hayward, California that originally expired in April 2018. The Company has entered into lease amendments that extend the lease commitment through June 2025.
Contractual Obligations and Commercial Commitments On October 1, 2016, the Company entered into an operating lease for office space in Hayward, California that originally expired in April 2018.
We expect that our research and development expenses may increase due to the continued development of the OPMD program. We had no borrowings for the years ended June 30, 2023 and 2022 and do not currently have a credit facility. As of June 30, 2023, we had cash and cash equivalents of $2.5 million.
The Company had accumulated losses of $190.3 million as of June 30, 2024. We expect that our research and development expenses may increase due to the continued development of the OPMD program. We had no borrowings for the years ended June 30, 2024 and 2023 and do not currently have a credit facility.
The following table sets forth a summary of our revenues for each of the periods set forth below: Year Ended June 30, 2023 2022 (US$’000) Revenues from customers $ 75 $ 73 Total revenues $ 75 $ 73 During the year ended June 30, 2023, the Company recognized $75 thousand in customer revenues, as compared to $73 thousand for the comparable year ended June 30, 2022.
The following table sets forth a summary of our revenues for each of the periods set forth below: Year Ended June 30, 2024 2023 (US$’000) Revenues from customers $ — $ 75 Total revenues $ — $ 75 85 Table of Contents During the year ended June 30, 2024, the Company did not recognize any customer revenues, as compared to $75 thousand for the comparable year ended June 30, 2023.
Cash in excess of immediate requirements is invested in accordance with our investment policy, primarily with a view to liquidity and capital preservation. Currently, our cash and cash equivalents are held in bank accounts.
As of June 30, 2024, we had cash and cash equivalents of $50.9 million. Cash in excess of immediate requirements is invested in accordance with our investment policy, primarily with a view to liquidity and capital preservation. Currently, our cash and cash equivalents are held in bank accounts.
The Company received gross proceeds of approximately $14.3 million and net proceeds of approximately $12.7 million from the offering. 85 Table of Contents September 2022 Capital Raise On September 15, 2022, the Company announced the closing of an underwritten public offering of common stock and common stock equivalents (the September 2022 Capital Raise”).
April 2021 Capital Raise On April 30, 2021, the Company announced the closing of an underwritten public offering of common stock and common stock equivalents (the “April 2021 Capital Raise”). The Company received gross proceeds of approximately $14.3 million and net proceeds of approximately $12.7 million from the offering.
The following table sets forth a summary of the net cash flow activity for each of the periods set forth below: Year Ended June 30, 2023 2022 (US$’000) Net cash provided by (used in): Operating activities $ (18,012 ) $ (15,899 ) Investing activities (1 ) (13 ) Financing activities 16,015 — Effects of exchange rate changes on cash, cash equivalents, and restricted cash 412 204 Net decrease in cash, cash equivalents, and restricted cash $ (1,586 ) $ (15,708 ) 88 Table of Contents Operating activities Net cash used in operating activities for the year ended June 30, 2023 was $18.012 million.
The following table sets forth a summary of the net cash flow activity for each of the periods set forth below: Year Ended June 30, 2024 2023 (US$’000) Net cash provided by (used in): Operating activities $ (19,403 ) $ (18,012 ) Investing activities (179 ) (1 ) Financing activities 68,029 16,015 Effects of exchange rate changes on cash, cash equivalents, and restricted cash (8 ) 412 Net increase (decrease) in cash, cash equivalents, and restricted cash $ 48,439 $ (1,586 ) Operating activities Net cash used in operating activities for the year ended June 30, 2024 was $19.4 million.
Net cash used in operating activities for the year ended June 30, 202 was $15.899 million. Net cash used in operating activities was primarily the result of our net loss, change in working capital, depreciation and amortization, and share-based compensation expense.
Net cash used in operating activities for the year ended June 30, 2023 was $18.0 million. Net cash used in operating activities was primarily the result of our net loss, partially offset by share-based compensation expense, changes in working capital, and depreciation and amortization.
The Company has incurred cumulative losses and negative cash flows from operations since our predecessor’s inception in 1995, except for the year ended June 30, 2019 where we had net income of $2.609 million and generated positive cash flows of $4.790 million from operating activities. The Company had accumulated losses of $167.9 million as of June 30, 2023.
The Company expects to continue to incur additional operating losses in the foreseeable future. The Company has incurred cumulative losses and negative cash flows from operations since our predecessor’s inception in 1995, except for the year ended June 30, 2019 where we had net income of $2.6 million and generated positive cash flows of $4.8 million from operating activities.
Investing activities Net cash used in investing activities for the years ended June 30, 2023 and 2022 was $1 thousand and $13 thousand, respectively, and primarily related to purchases of equipment. Financing activities Net cash provided by financing activities was $16.015 million and zero for the years ended June 30, 2023 and 2022, respectively.
Investing activities Net cash used in investing activities for the years ended June 30, 2024 and 2023 was $179 thousand and $1 thousand, respectively, and relates to purchases of laboratory equipment. Financing activities Net cash provided by financing activities was $68.0 million and $16.0 million for the years ended June 30, 2024 and 2023, respectively.
We are subject to the risks inherent in the development of new gene therapy products, and we may encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect our business. On August 11, 2023, the Company announced the closing of an underwritten public offering of common stock and common stock equivalents.
We are subject to the risks inherent in the development of new gene therapy products, and we may encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect our business. On April 22, 2024, the Company announced the closing of a private investment in public equity (PIPE) financing.
Foreign Currency Translation and Other Comprehensive Income (Loss) The Company’s functional currency and reporting currency is the United States dollar. BBL’s functional currency is the Australian dollar (AUD). Assets and liabilities are translated at the exchange rate in effect at the balance sheet date. Revenues and expenses are translated at the average rate of exchange prevailing during the reporting period.
BBL’s functional currency is the Australian dollar (AUD). Assets and liabilities are translated at the exchange rate in effect at the balance sheet date. Revenues and expenses are translated at the average rate of exchange prevailing during the reporting period. Equity transactions are translated at each historical transaction date spot rate.
Additionally, the achievement of permanent gene silencing and gene replacement may significantly reduce the risk of patient non-compliance during the course of medical management of potentially fatal clinical disorders.
Additionally, the achievement of permanent gene silencing and gene replacement may significantly reduce the risk of patient non-compliance during the course of medical management of potentially fatal clinical disorders. Available Information Our telephone number is (510) 780-0819, and our Internet website is www.benitec.com.
The year-over-year decrease relates primarily to lower listing and filing fees and stock-based compensation. 87 Table of Contents Other Income (Loss) The following table sets forth a summary of our other income (loss) for each of the periods set forth below: Year Ended June 30, 2023 2022 (US$’000) Other Loss: Foreign currency transaction loss (415 ) (232 ) Interest expense, net (33 ) (32 ) Other expense, net (30 ) (79 ) Unrealized loss on investment (3 ) (11 ) Total other loss, net (481 ) (354 ) The other loss, net during the year ended June 30, 2023 totaled $481 thousand, which consists of foreign currency transaction loss, interest expense, other expense, net, and unrealized loss on investment.
Other Income (Loss) The following table sets forth a summary of our other income (loss) for each of the periods set forth below: Year Ended June 30, 2024 2023 (US$’000) Other Loss: Foreign currency transaction gain (loss) $ 40 $ (415 ) Interest income (expense), net 904 (33 ) Other expense, net (204 ) (30 ) Unrealized loss on investment (1 ) (3 ) Total other income (loss), net $ 739 $ (481 ) The other income, net during the year ended June 30, 2024 totaled $739 thousand, which consists of foreign currency transaction gain, interest income, other expense, net, and unrealized loss on investment.
Royalties, milestone payments and other license fees We are required to pay royalties, milestone payments and other license fees in connection with our licensing of intellectual property from third parties, including as discussed below.
Royalties, milestone payments and other license fees We are required to pay royalties, milestone payments and other license fees in connection with our licensing of intellectual property from third parties, including as discussed below. 84 Table of Contents Foreign Currency Translation and Other Comprehensive Income (Loss) The Company’s functional currency and reporting currency is the United States dollar.
For the year ended June 30, 2023, cash from financing activities related to the issuance of ordinary shares and pre-funded warrants, and common warrants; including $17.884 million in gross proceeds from the September 2022 Capital Raise, partially offset by $1.869 million of shares and warrant issuance costs.
For the year ended June 30, 2024, cash from financing activities related primarily to the issuance of common shares, pre-funded warrants, and common warrants; including $30.9 million and $40.0 million in gross proceeds from the August 2023 and April 2024 Capital Raises, respectively; partially offset by $3.0 million and $2.9 million, respectively, of related issuance costs.
The Company has not experienced any material differences between accrued costs and actual costs incurred. Share-Based Compensation The Company records share-based compensation in accordance with ASC 718, “ Stock Compensation ”. ASC 718 requires the fair value of all share- based employee compensation awarded to employees and non-employees to be recorded as an expense over the related requisite service period.
The Company has not experienced any material differences between accrued costs and actual costs incurred. 90 Table of Contents Share-Based Compensation The Company records share-based compensation in accordance with ASC 718, “ Stock Compensation ”.
The change is primarily due to a decrease in license fees. During the year ended June 30, 2023, we incurred $12.774 million in research and development expenses, as compared to $11.272 million for the comparable year ended June 30, 2022. The increase in research and development expenses relates primarily to the OPMD project.
The credit to expense during the year ended June 30, 2024 relates to the reversal of accruals for license fees no longer due. During the year ended June 30, 2024, we incurred $15.6 million in research and development expenses, as compared to $12.8 million for the comparable year ended June 30, 2023.
The Company received gross proceeds of approximately $30.9 million and net proceeds of approximately $28.6 million from the offering. Results of Operations Revenues from customers In the fiscal year ended June 30, 2023, the Company generated funds primarily from capital raising activities. The Company has not generated any revenues from the sales of products.
Results of Operations Revenues from customers In the fiscal year ended June 30, 2024, the Company generated funds primarily from capital raising activities. The Company has not generated any revenues from the sales of products. Revenues from licensing fees and interest income are included in the revenue from customers line item on our statements of operations and comprehensive income (loss).
Revenues from licensing fees and interest income are included in the revenue from customers line item on our statements of operations and comprehensive income (loss). Our licensing fees have been generated through the licensing of our ddRNAi technology to biopharmaceutical companies.
Our licensing fees have been generated through the licensing of our ddRNAi technology to biopharmaceutical companies.
On August 11, 2023, the Company closed an underwritten public offering resulting in $28.6 million in net proceeds to the Company. We estimate that our cash and cash equivalents will be sufficient to fund the Company’s operations for at least the next twelve months after the date that this Annual Report is filed.
We estimate that our cash and cash equivalents will be sufficient to fund the Company’s operations for at least the next twelve months after the date that this Annual Report is filed. While we have established some licensing arrangements, we do not have any products approved for sale and have not generated any revenue from product sales.
The Company enters into contracts in the normal course of business with third-party contract research organizations, contract development and manufacturing organizations and other service providers and vendors. These contracts generally provide for termination on notice and, therefore, are cancellable contracts and not considered contractual obligations and commitments.
The Company has entered into lease amendments that extend the lease commitment through June 2025. 89 Table of Contents The Company enters into contracts in the normal course of business with third-party contract research organizations, contract development and manufacturing organizations and other service providers and vendors.
During the year ended June 30, 2022, other loss, net, totaled $354 thousand. Foreign currency transaction loss has increased due to a change in foreign exchange rates. Interest expense was essentially unchanged year-over-year. The decrease in other expense, net relates to recognition of a tax refund.
During the year ended June 30, 2023, other loss, net, totaled $481 thousand. The foreign currency transaction gain for the year ended June 30, 2024, as compared to the loss for the year ended June 30, 2023, reflects a change in foreign exchange rates.
For the years ended June 30, 2023, and 2022, the Company incurred net losses of $19.56 million and $18.21 million, and used net cash of $18.01 million and $15.90 million in operations, respectively. The Company expects to continue to incur additional operating losses in the foreseeable future.
Liquidity and Capital Resources The accompanying consolidated financial statements have been prepared assuming that the Company will continue as a going concern. For the years ended June 30, 2024, and 2023, the Company incurred net losses of 87 Table of Contents $21.8 million and $19.6 million, and used net cash of $19.4 million and $18.0 million in operations, respectively.
This ASU represents a significant change in the accounting for credit losses model by requiring immediate recognition of management’s estimates of current expected credit losses (CECL). Under the prior model, losses were recognized only as they were incurred. The Company has determined that it has met the criteria of a smaller reporting company (“SRC”) as of November 15, 2019.
Recent Accounting Pronouncements Accounting Standards recently adopted ASU 2016-13—In June 2016, the FASB issued ASU No. 2016-13: “ Financial Instruments-Credit Losses (Topic 326)”. This ASU represents a significant change in the accounting for credit losses model by requiring immediate recognition of management’s estimates of current expected credit losses (CECL).
General and administrative expense was $6.382 million and $6.646 million for the years ended June 30, 2023 and 2022, respectively.
The increase in research and development expenses relates to the ongoing clinical development of BB-301 for the treatment of OPMD. General and administrative expense totaled $7.0 million and $6.4 million for the years ended June 30, 2024 and 2023, respectively.
Removed
Re-domiciliation On April 15, 2020, or the Implementation Date, the Re-domiciliation of Benitec Limited, a public company incorporated under the laws of the State of Western Australia, or Benitec Limited, was completed in accordance with the Scheme Implementation Agreement, as amended and restated as of January 30, 2020, between Benitec Limited and us.
Added
The information on, or that can be accessed through, our website is not part of this Annual Report on Form 10-K and is not incorporated by reference herein.
Removed
As a result of the Re-domiciliation, the jurisdiction of incorporation was changed from Australia to Delaware, and Benitec Limited became our wholly owned subsidiary. 84 Table of Contents The Re-domiciliation was effected pursuant to a statutory scheme of arrangement under Australian law, or the Scheme, whereby on the Implementation Date, all of the issued and outstanding ordinary shares of Benitec Limited were exchanged for newly issued shares of our common stock, on the basis of one share of our common stock, par value $0.0001 per share, for every 300 ordinary shares of Benitec Limited issued and outstanding.
Added
September 2022 Capital Raise On September 15, 2022, the Company announced the closing of an underwritten public offering of common stock and common stock equivalents (the “September 2022 Capital Raise”). The Company received gross proceeds of approximately $17.9 million and net proceeds of approximately $16.0 million from the offering.
Removed
Holders of Benitec Limited’s American Depository Shares, or ADSs (each of which represented 200 ordinary shares), received two shares of our common stock for every three ADSs held. COVID-19 COVID-19 has been declared a pandemic by the World Health Organization and has spread to nearly every country, including Australia and the United States.
Added
April 2024 Capital Raise On April 22, 2024 we closed a private investment in public equity (PIPE) financing of common stock and common stock equivalents (the “April 2024 Capital Raise”). The Company received gross proceeds of approximately $40.0 million and net proceeds of approximately $37.1 million from the financing.
Removed
The impact of this pandemic has been and will likely continue to be extensive in many aspects of society, which has resulted in and will likely continue to result in significant disruptions to businesses and capital markets around the world.
Added
The year-over-year increase relates primarily to higher stock-based compensation, bonuses paid during the second quarter, and travel expenses ($300 thousand, $25 thousand, and $157 thousand, respectively).
Removed
The extent to which the coronavirus impacts us will depend on future developments, which are highly uncertain and cannot be predicted, including new information which may emerge concerning the severity of the coronavirus and its variants, and the actions to contain the coronavirus or treat its impact, including the effectiveness and adoption of vaccines for the virus, among others.
Added
Net interest income for the year ended June 30, 2024, in comparison to the loss reported for the year ended June 30, 2023, reflects the increase in the Company’s cash and cash equivalent balances.
Removed
Certain of our research and development efforts are conducted globally, including the ongoing development of our silence and replace therapeutic for the treatment of Oculopharyngeal Muscular Dystrophy (OPMD), and will be dependent upon our ability to continue our preclinical and clinical studies and related work despite the COVID-19 pandemic and any similar events.
Added
The increase in other expense relates to higher Delaware report filing fees ($160 thousand) and franchise taxes ($32 thousand), which are based on the Company’s stockholders’ equity. Unrealized loss on investment was due to lower fair market values of the Company’s investments.
Removed
We have collaborated with Biomics Biotechnologies Co., Ltd., or Biomics, pursuant to several collaboration agreements in relation to single-stranded RNA and shRNA sequences for treatment of hepatitis B.
Added
On April 22, 2024, the Company closed a private 88 Table of Contents investment in public equity (PIPE) financing resulting in $37.1 million in net proceeds to the Company.
Removed
In July 2015, we entered into an earn-out agreement with Biomics which confirmed Benitec’s ownership of certain patents resulting from the collaboration in exchange for an upfront payment and equity issuance to Biomics and a share of certain future licensing revenue received by Benitec.
Added
These contracts generally provide for termination on notice and, therefore, are cancellable contracts and not considered contractual obligations and commitments.
Removed
Equity transactions are translated at each historical transaction date spot rate.
Added
ASC 718 requires the fair value of all share- based employee compensation awarded to employees and non-employees to be recorded as an expense over the related requisite service period. The Company values employee and non-employee share-based compensation at fair value using the Black-Scholes Option Pricing Model.
Removed
Other Comprehensive Income (Loss) for all periods presented includes only foreign currency translation gains (losses). April 2021 Capital Raise On April 30, 2021, the Company announced the closing of an underwritten public offering of common stock and common stock equivalents (the “April 2021 Capital Raise”).
Added
Under the prior model, losses were recognized only as they were incurred. The Company adopted this ASU effective July 1, 2023 and determined that its impact on the accompanying consolidated financial statements is immaterial.
Removed
The Company also anticipates an increase in expenses relating to accounting, legal and regulatory-related services associated with maintaining compliance with exchange listing and SEC requirements, director and officer insurance premiums and other costs associated with being a domestic public company after the Re-domiciliation.
Added
Recently Issued Accounting Standards not yet adopted In December 2023, the FASB issued ASU No. 2023-09, “Income Taxes (Topic 740)— Improvements to Income Tax Disclosures ”, which enhances the transparency, effectiveness and comparability of income tax disclosures by requiring consistent categories and greater disaggregation of information related to income tax rate reconciliations and the jurisdictions in which income taxes are paid.
Removed
Unrealized loss on investment was due to lower fair market values of the Company’s investments. Liquidity and Capital Resources The accompanying consolidated financial statements have been prepared assuming that the Company will continue as a going concern.
Added
This guidance is effective for annual periods beginning after December 15, 2024 with early adoption permitted. The Company is currently evaluating the impact of the ASU on its income tax disclosures within the consolidated financial statements.
Removed
While we have established some licensing arrangements, we do not have any products approved for sale and have not generated any revenue from product sales. We do not know when, or if, we will generate any revenue from product sales.
Added
In November 2023, the FASB issued ASU No. 2023-07, “ Segment Reporting (Topic 280)—Improvements to Reportable Segment Disclosures”, which improves reportable segment disclosure requirements, primarily through enhanced disclosures about significant segment expenses. This ASU also expands disclosure requirements to enable users of financial statements to better understand the entity’s measurement and assessment of segment performance and resource allocation.
Removed
The Company values employee and non-employee share-based compensation at fair value using the Black-Scholes Option Pricing Model. Recent Accounting Pronouncements Accounting Standards recently adopted None. New Accounting Standards and Interpretations not yet mandatory or early adopted ASU 2016-13 —In June 2016, the FASB issued ASU No. 2016-13: “ Financial Instruments—Credit Losses (Topic 326)”.
Added
This guidance is effective for fiscal years beginning after December 15, 2023, and interim periods within fiscal years beginning after December 15, 2024, with early adoption permitted. The Company is currently evaluating the impact of the ASU on its disclosures within the consolidated financial statements.
Removed
As such, ASU 2019-10: “ Financial Instruments-Credit Losses, Derivatives and Hedging, and Leases: Effective Dates ” amended the effective date for the Company to be for reporting periods beginning after December 15, 2022. The Company will adopt this ASU effective July 1, 2023.

Other BNTC 10-K year-over-year comparisons