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Item 1. Business

2025-09-22 compared with 2024-09-26 · 51 added, 175 removed, 489 unchanged (32% of the section changed)

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Benitec Biopharma Inc.

(“Benitec” or the “Company” or in the third person, “we” or “our”) is a clinical-stage biotechnology company focused on the advancement of novel genetic medicines with headquarters in Hayward, California.

(“Benitec” or the “Company” or in the first person, “we” or “our”) is a clinical-stage biotechnology company focused on the advancement of novel genetic medicines with headquarters in Hayward, California.

The proprietary platform, called DNA-directed RNA interference, or ddRNAi, combines RNA interference, or RNAi, with gene therapy to create medicines that facilitate sustained silencing of disease-causing genes following a single administration.

The unique therapeutic constructs also enable the simultaneous delivery of wildtype replacement genes, facilitating the proprietary “silence and replace” approach to the treatment of genetically defined diseases.

The Company is developing a silence and replace-based therapeutic (BB-301) for the treatment of Oculopharyngeal Muscular Dystrophy (OPMD), a chronic, life- threatening genetic disorder.

We are developing a silence and replace-based therapeutic (BB-301) for the treatment of Oculopharyngeal Muscular Dystrophy (OPMD), a chronic, life-threatening genetic disorder.

BB-301 is a silence and replace-based genetic medicine currently under development by Benitec.

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BB-301 has been granted Orphan Drug Designation in the United States and the European Union.

Our Strengths

We believe that the combination of our proprietary ddRNAi and silence and replace technology, and our deep expertise in the design and development of genetic medicines, will enable us to achieve and maintain a leading position in gene silencing and gene therapy for the treatment of human disease.

Our key strengths include:

A first mover advantage for silence and replace-based therapeutics;

A proprietary ddRNAi-based silence and replace technology platform that may potentially enable the serial development of single- administration therapeutics capable of facilitating sustained, long-term silencing of disease-causing genes and concomitant replacement of wild type gene function;

A proprietary AAV vector technology which improves the endosomal escape capability of virus produced in insect cells using a baculovirus system.

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;

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.

We endeavor to become the leader in discovery, development, and commercialization of silence and replace-based therapeutic agents.

We apply the following general strategy to drive the Company towards these goals:

Selectively develop proprietary and partnered programs;

Continue to explore and secure research and development partnerships with global biopharmaceutical companies supported by the differentiated nature of our scientific platform and intellectual property portfolio.

Our senior leadership team will continue to explore partnership opportunities with global biopharmaceutical companies, as we expect that the unique attributes of the proprietary ddRNAi and silence and replace approaches, and the breadth of potential clinical indications amenable to our proprietary methods, to support the formation of collaborations over a broad range of diseases with significant unmet medical need.

We seek to actively protect our intellectual property and proprietary technology.

These efforts are central to the growth of our business and include:

Seeking and maintaining patents claiming our ddRNAi and silence and replace technologies and other inventions relating to our specific products in development or that are otherwise commercially and/or strategically important to the development of our business;

Protecting and enforcing our intellectual property rights;

Strategically licensing intellectual property from third parties to advance development of our product candidates.

The following table sets forth our current product candidate and the development status:

Oculopharyngeal Muscular Dystrophy

We are developing BB-301 for the treatment of Oculopharyngeal Muscular Dystrophy (OPMD) with moderate dysphagia.

We are developing BB-301 for the treatment of Oculopharyngeal Muscular Dystrophy (OPMD)-related 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.

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.

The first study subject was safely treated in the BB-301 Phase 1b/2a clinical trial (NCT06185673) in November 2023.

The second study subject was safely treated in February 2024.

The third study subject was safely treated in October 2024.

The fourth study subject was safely treated in December 2024.

The fifth study subject was safely treated in February 2025, and the sixth study subject was safely treated in April 2025.

BB-301 is the lead investigational gene therapy agent under development by Benitec, and the key attributes of BB-301 are outlined in Figure 3.

BB-301 is a first-in-class genetic medicine employing the “silence and replace” approach for the treatment of OPMD.

OPMD is an insidious, autosomal-dominant, late-onset, degenerative muscle disorder that typically

presents in patients at 40-to-50 years of age.

OPMD is an insidious, autosomal-dominant, late-onset, degenerative muscle disorder that typically presents in patients at 40-to-50 years of age.

The disease is characterized by progressive swallowing difficulties (dysphagia) and eyelid drooping (ptosis).

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While OPMD is a rare medical disorder, we believe the commercial opportunity for a safe and efficacious therapeutic agent in this clinical indication exceeds $1 billion over the course of the commercial life of the product.

Investigational therapies that have been explored, unsuccessfully, in the past include:

Intravenous administration of trehalose;

The use of autologous myoblast transplant.

BB-301 is our Lead, Silence and Replace-Based, OPMD Therapeutic Agent

BB-301 is composed of a modified AAV serotype 9 (AAV9) capsid that expresses a bifunctional construct under the control of a single muscle specific Spc5-12 promoter to achieve co-expression of both the codon-optimized PABPN1 mRNA and two shmiR molecules directed against wild type and mutant PABPN1.

PABPN1 mRNA and two shmiR molecules directed against wild type and mutant PABPN1.

BB-301 is designed to correct the genetic defect underlying OPMD following a single localized administration.

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BB-301 is also engineered to drive the simultaneous expression of a codon-optimized, siRNA-resistant, version of the wild type PABPN1 gene (Figure 4).

In collaboration with researchers at the Royal Holloway University of London and the Institut de Myologie in Paris, we developed a ddRNAi construct expressing three shRNAs against three distinct regions of PABPN1 mRNA and observed effective silencing of the PABPN1 gene in vitro using this ddRNAi construct.

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.

Additional shmiRs have also been designed for the original shRNA developed in collaboration with Royal Holloway University of London and the Institut de Myologie.

The ‘silence and replace’ construct, designated BB-301, incorporates the two best performing shmiRs, and the gene expression construct that produces a siRNA-resistant version of the wild type PABPN1 gene, under the control of a muscle-specific promoter.

The mechanism of action of BB-301 is shown in 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.

These nonclinical results were published in Nature Communications in April 2017.

In subsequent studies, Benitec demonstrated in a key nonclinical model (the A17 mouse model) that a single intramuscular injection of BB-301 results in robust intracellular silencing of PABPN1 protein production and concomitant expression of the normal, biologically functional PABPN1 protein.

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

Dose-Dependent shRNA Expression

Dose-Dependent PABPN1 Inhibition and Transgene Expression

Dose-Dependent Decreases in Intranuclear Inclusions

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.

The BB-301 Pilot Dosing Study was the first of two planned CTA-enabling and IND-enabling studies that were designed to be conducted in large animals.

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, along with the subsequent GLP Toxicology and Biodistribution Study, were conducted in canine subjects and were carried out to support the validation and optimization of the newly designed method of BB-301 administration, confirm the efficiency of vector transduction and transgene expression in the key tissue compartments underlying the natural history of OPMD, confirm the optimal drug doses in advance of initiation of human clinical studies, and facilitate observation of key toxicological data-points.

The BB-301 Pilot Dosing Study was designed as an 8-week study in Beagle dogs to confirm the transduction efficiency of BB-301 upon administration via direct intramuscular injection into specific anatomical regions of the pharynx through the use of an open surgical procedure.

This new route of BB-301 administration was developed in collaboration with key surgical experts in the field of Otolaryngology, and this novel method of BB-301 dosing was implemented to significantly enhance the ability of a treating physician to accurately administer the AAV-based investigational agent to the muscles that underlie the characteristic deficits associated with the progression of OPMD.

It is important to note that prior nonclinical studies of BB-301 have reproducibly validated the robust biological activity achieved following direct intramuscular injection.

As an example, direct injection of BB-301 into the tibialis anterior muscles of A17 mice facilitated robust transduction of the targeted skeletal muscle cells and supported complete remission of the OPMD disease phenotype in this animal model.

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;

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.

The Pilot Dosing Study evaluated the safety and biological activity of two concentrations of BB-301 (1.0+E13 vg/mL and 3.0+E13 vg/mL) across three distinct doses (1.0+E13 vg/mL, 3.0+E13 vg/mL with a low injection volume, and 3.0+E13 vg/mL with a high injection volume) following direct intramuscular injection into the Hypopharyngeal (HP) muscles and the Thyropharyngeal (TP) muscles of Beagle dogs via the use of a proprietary delivery device employed in an open surgical procedure.

The HP muscle in Beagle dogs corresponds to the Middle Pharyngeal Constrictor muscle in human subjects, and the TP muscle in Beagle dogs corresponds to the Inferior Pharyngeal Constrictor muscle in human subjects.

Atrophy, fibrosis, and the presence of intranuclear inclusions characterize the Middle Pharyngeal Constrictor muscles and the Inferior Pharyngeal Constrictor muscles of human subjects diagnosed with OPMD.

BB-301 was injected into the pharyngeal muscles of the Beagle dog subjects only on Day 1 of the Pilot Dosing Study, and the corresponding canine pharyngeal muscles were harvested for analysis after 8 weeks of observation post-dosing.

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:

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.

siRNA13 Expression Levels for BB-301 within Pharyngeal Muscle Tissues and siRNA17 Expression Levels for BB-301 within Pharyngeal Muscle Tissues

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.

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.

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 Benitec team worked to optimize the route and method of administration of BB-301 and to refine the core analytical methods employed following the completion of dosing.

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).

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:

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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.

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.

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.

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.

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.

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.

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.

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.

Key Opinion Leaders (KOLs) participating in the recent BB-301 Research and Development Day webcast (April 2024) highlighted VFSS assessments of TPR and the Subject-Reported Outcome SSQ Total Score as the central markers of value for the long-term evaluation of clinically meaningful improvement in subjects diagnosed with OPMD.

Closing of Private Placement and Entry into Board Designation Letter.

On April 22, 2024 we closed a private investment in public equity (PIPE) financing (the “April 2024 private placement”) 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 institutional accredited investors.

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.

In connection with the April 2024 private placement, we entered into a Voting Commitment Agreement with the purchasers in the private placement (the “Voting Commitment Agreement”).

Pursuant to the Voting Commitment Agreement, the Company was obligated to use its reasonable best efforts to obtain stockholder approval of the exercise of the Pre-Funded Warrants issued in the private placement and the warrants issued in the Company’s underwritten public offerings on September 15, 2022 and August 11, 2023 (the “Existing Warrants,” and together with the Pre-Funded Warrants, the “Warrants”) in accordance with the rules of the Nasdaq Stock Market which otherwise would be subject to the Beneficial Ownership Limitation (the “Stockholder Approval”).

The Company obtained the Stockholder Approval by the Company’s stockholders at the Company’s Special Meeting of Stockholders held August 29, 2024.

As a result of the Stockholder Approval, holders of the Existing Warrants can waive the 19.99% beneficial ownership limitation that would otherwise be applicable to such holder.

On or about September 26, 2024, Suvretta Capital Management, LLC (“Suvretta”) waived the limitation but is now subject to a 49.9% beneficial ownership limitation.

We also entered into a Board Designation Side Letter (the “Board Designation Agreement”) with Suvretta Capital at the closing of the private placement.

Pursuant to the Board Designation Agreement, the Company agreed to consider for appointment and appoint Kishen Mehta to the Company’s Board of Directors (the “Board”) upon consummation of the transactions contemplated by the Securities Purchase Agreement, and in such board class as determined by the Company prior to his appointment.

Mehta was appointed to the Board as a Class I director on June 26, 2024.

Pursuant to the Board Designation Agreement, Suvretta agreed that (1) in connection with the closing of the Private Placement, (i) the Company and Suvretta will take such action as may be required to permit Suvretta to exercise its Warrants up to the 19.99% Beneficial Ownership Limitation, and (ii) Suvretta would vote all of its shares of Common Stock owned on the record date for such votes in favor of (1) all of the Company’s director nominees for election to the Board at the Company’s annual meetings of stockholders to be held during the term of the Board Designation Agreement, and (2) the proposal seeking the Stockholder Approval pursuant to the Voting Commitment Agreement at any annual or special meeting of the Company where such proposal is presented, if permitted by applicable law or regulations.

Intellectual Property

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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 .

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.

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 and packaged within a AAV9 vector with a modified capsid protein.

BB-301 is administered to the pharyngeal muscle via an interoperative method and using a proprietary injection needle design for optimized delivery.

These five families cover:

(i) the individual shmiRs comprised within the OPMD therapeutic candidate, BB-301, under development at Benitec, (ii) the ‘silence and replace’ construct within BB-301, (iii) treatment strategies for OPMD that silence PABPN1 which is causative for OPMD and replace with functional PABPN1, (iv) Benitec’s proprietary AAV vector for delivery of BB-301, (v) Benitec’s proprietary injection needle for delivery of BB-301 to the pharyngeal muscle of OPMD patients, (vi) pre-filled multi-injection devices used for delivery of BB-301, and (vii) an interoperative method to enable delivery of BB-301 to the pharyngeal muscle of OPMD patients.

In this regard, 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 and packaged within an AAV9 vector with a modified capsid protein.

BB-301 is administered to the pharyngeal muscle via an interoperative method using a proprietary injection needle design for optimized delivery.

Multi-injection delivery devices fitted with the proprietary injection needle and pre-filled with appropriate dosage volumes of BB-301 have been developed for delivery of BB-301 to the pharyngeal muscle of affected subject via the intraoperative method.

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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).

This PCT application and the related U.S.

application and the related U.S.

priority document were filed solely in the name of Benitec, and this family entered the national/regional phase in August/September 2022.

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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.

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 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.

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The trademarks that we use in connection with our business include the following:

Application or

Country or Territory

Trademark (program)

Application or

Registration number

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European Union

GIVING DISEASE THE SILENT TREATMENT

GIVING DISEASE THE SILENT

United Kingdom

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We have not yet established sales, marketing or product distribution operations because our product candidates are in preclinical or clinical development.

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

third parties.

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 third parties.

In certain cases, we may market an approved product directly worldwide or in selected geographical segments.

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The RMAT designation gives the sponsor of a new investigational biologic access to increased meeting opportunities with the FDA, in a manner comparable to those offered to sponsors of therapies designated as “breakthrough therapies” by the FDA.

Because the designated products meet the criteria for unmet medical need in the treatment of a serious condition, they may be eligible for priority review, in which the initial assessment of the BLA is reduced from 12 months to eight months, and accelerated approval, which bases approval on an effect on a predictive surrogate endpoint or an intermediate clinical endpoint.

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.

months, and accelerated approval, which bases approval on an effect on a predictive surrogate endpoint or an intermediate clinical endpoint.

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.

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.

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Phase II clinical trials are typically well- controlled, closely monitored, and conducted in a limited patient population, usually involving no more than several hundred participants.

Phase IIa trials provide information on the impact of dose ranging on safety, biomarkers and proof of concept, while Phase IIb trials are patient dose-ranging efficacy trials.

Phase IIa trials provide information on the impact of dose ranging on

safety, biomarkers and proof of concept, while Phase IIb trials are patient dose-ranging efficacy trials.

Phase III clinical trials are controlled clinical trials conducted in an expanded patient population at geographically dispersed clinical trial sites.

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.

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 hundred to several thousand participants.

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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.

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.

changes in distributed products.

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.

In November 2013, the Drug Quality and Security Act, or DQSA, became law and establishes requirements to facilitate the tracing of prescription drug and biological products through the supply distribution chain.

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Failure to comply with these requirements can result in adverse publicity, warning or untitled letters, corrective advertising, injunctions, potential civil and criminal penalties, criminal prosecution, and agreements with governmental agencies that materially restrict the manner in which a company promotes or distributes products.

Pediatric Research Equity Act

Under the Pediatric Research Equity Act, or PREA, as amended, a BLA or supplement must contain data to assess the safety and efficacy of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

Manufacturers must submit a pediatric study plan to the IND not later than 60 days after the end-of-phase 2 meeting with the FDA;

if there is no such meeting, before the initiation of any phase 3 studies or a combined phase 2 and phase 3 study;

or if no such study will be conducted, no later than 210 days before a marketing application or supplement is submitted.

The intent of PREA is to compel sponsors whose products have pediatric applicability to study those products in pediatric populations, rather than ignoring pediatric indications for adult indications that could be more economically desirable.

The FDA may grant deferrals for submission of data or full or partial waivers.

By its terms, PREA does not apply to any product for an indication for which orphan designation has been granted, unless the FDA issues regulations stating otherwise.

Because the FDA has not issued any such regulations, submission of a pediatric assessment is not required for an application to market a product for an orphan-designated indication.

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.

Patent Term Restoration and Marketing Exclusivity

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patents may be eligible for limited patent term extension under the Hatch-Waxman Amendments.

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.

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.

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Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, can be shown through analytical studies, animal studies, and a clinical study or studies.

Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product and, for products administered multiple times, the biologic and the reference biologic may be switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic.

Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate

that it can be expected to produce the same clinical results as the reference product and, for products administered multiple times, the biologic and the reference biologic may be switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic.

However, complexities associated with the larger, and often more complex, structure of biological products, as well as the process by which such products are manufactured, pose significant hurdles to implementation that are still being worked out by the FDA.

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The European Union also provides opportunities for market exclusivity.

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.

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.

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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.

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.

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 loss.” Gains and losses resulting from foreign currency translation are included in the consolidated statements of operations and comprehensive loss as other comprehensive income (loss).

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 Company received gross proceeds of approximately $14.3 million and net proceeds of approximately $12.7 million from the offering.

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 Company received gross proceeds of approximately $17.9 million and net proceeds of approximately $16.0 million from the offering.

August 2023 Capital Raise

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The common warrants were immediately exercisable at a price per share of common stock of $3.86 and expire on the fifth anniversary of such initial exercisable date.

The combined purchase price for each share of common stock and accompanying common warrant was $1.93, which was allocated as $1.9299 per share of common stock and $0.0001 per common warrant.

The combined purchase price for each share of common stock and accompanying common warrant was $1.93, which was allocated as $1.9299 per share of common stock and

$0.0001 per common warrant.

Each pre-funded warrant was sold together with one common warrant at a combined price of $1.9299, which was allocated as $1.9298 per pre-funded warrant and $0.0001 per common warrant.

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Net proceeds from the offering, including the impact of the underwriter’s partial exercise of its option and net of underwriting discounts, commissions, and other offering expenses, totaled $27.9 million.

The Company has outstanding Series 2 warrants (the “Series 2 Warrants”) which are currently exercisable into 1,733,503 shares of common stock after giving effect to the Reverse Stock Split and exercises as of March 31, 2024.

The Company has outstanding Series 2 warrants (the “Series 2 Warrants”) which are currently exercisable into 101,537 shares of common stock after giving effect to the Reverse Stock Split and exercises as of June 30, 2025.

The Series 2 Warrants contain an exercise price adjustment mechanism providing that certain issuances of common stock (or common stock equivalents) if made at a price lower than the existing exercise price of $11.22 of such Series 2 Warrants, would reset the exercise price to such lower price.

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April 2024 Capital Raise

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.

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.

The pre-funded warrants were immediately exercisable until exercised in full at an exercise price of $0.0001 per share of common stock.

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Net proceeds, net of commissions and other offering expenses, totaled approximately $37.1 million.

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.

Of these full-time employees, 14 are engaged in research and development activities and 2 are engaged in finance, legal, human resources, facilities and general management.

March 2025 Capital Raise

On March 25, 2025, we entered into an Underwriting Agreement with Leerink Partners LLC and TD Securities (USA) LLC, as representatives of the several underwriters named therein, pursuant to which we agreed to issue and sell, in an underwritten offering by us (the “Underwritten Offering”), (i) 1,143,000 shares of our common stock at a purchase price to investors of $13.00 per share, and (ii) pre-funded warrants to purchase 300,000 shares of Common Stock at an exercise price of $0.0001 per share at a purchase price to investors of $12.999 per warrant, and a Securities Purchase Agreement with Averill Master Fund, Ltd.

and Averill Madison Master Fund, Ltd.

(together, the “Purchasers”), pursuant to which we agreed to issue and sell to the Purchasers an aggregate of 900,000 shares of Common Stock at a purchase price of $13.00 per share in a registered direct offering (the “Direct Offering,” and together with the Underwritten Offering, the “Offerings”), the same price per share as the offering price in the Underwritten Offering.

We received gross proceeds of approximately $30.5 million and net proceeds of approximately $28.2 million from the Offerings.

As of June 30, 2025, we had 19 full-time employees, one of whom has an MD, PhD, five have a PhD, four have a Master’s Degree, two have a biotechnology certificate, and one has an MBA, for a total of 13 with post-graduate degrees.

Of these full-time employees, 14 are engaged in research and development activities and five are engaged in finance, legal, human resources, facilities and general management.

None of our employees are represented by any labor union.

As of June 30, 2024, 15 employees were located in the United States and 1 employee in Australia.

All employees are in the United States.

Corporate Information

We were incorporated as a Delaware corporation on November 22, 2019 and completed the Re-domiciliation April 15, 2020.

We were incorporated as a Delaware corporation on November 22, 2019, and completed our re-domiciliation from Australia to the United States of America on 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.

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.

As a result of the Re-domiciliation, our jurisdiction of incorporation was changed from Australia to Delaware, and Benitec Limited became our wholly owned subsidiary.

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.

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.

Our common stock began trading on The Nasdaq Capital Market, or Nasdaq, at the start of trading on the Implementation Date under the symbol “BNTC.”

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All fractional shares were rounded up to the nearest whole share with respect to outstanding shares of common stock.

All share and earnings per share amounts presented in this Form 10-Q reflect the impact of this reverse split.

All share and earnings per share amounts presented in this Form 10-K reflect the impact of this reverse split.

Available Information

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business